Publications by authors named "Vishwa Mohan Katoch"

39 Publications

Efficacy of IVRS-based mHealth intervention in reducing cardiovascular risk in metabolic syndrome: A cluster randomized trial.

Diabetes Metab Syndr 2021 Jun 21;15(5):102182. Epub 2021 Jun 21.

Academic Research Development Unit, Rajasthan University of Health Sciences, 302033, Jaipur, India.

Aims: Efficacy of mobile-phone based intervention for reducing cardiovascular risk in metabolic syndrome (MetSyn).

Methods: We screened adults 20-60 years in 10 villages in India for MetSyn using stratified cluster sampling. Lifestyle and biochemical risk factors were assessed. International Harmonized Criteria were used for diagnosis. Villages were randomized with 5 each in control and intervention groups. Interactive voice response system (IVRS) in Hindi was developed. In intervention clusters two messages for promotion of healthy lifestyle and medical treatment were broadcast daily over 12-months and risk factors reassessed.

Results: 1012/1200(84%) persons were screened and MetSyn diagnosed in 286(28.3%). Villages were divided into 5 control(n = 136) and 5 intervention(n = 147) clusters. Baseline characteristics in both clusters were similar. Acceptability of intervention was >60% in 80% participants. At 12 months, significantly greater participants in intervention vs control clusters had healthier lifestyle (healthy diet 28.8vs14.7%, physical activity 25.9vs13.1%, tobacco 13.7vs32.5%), anthropometry (waist circumference 85.7 ± 6.3vs88.6 ± 14.0 cm, body mass index 21.9 ± 2.8vs23.1 ± 2.9 kg/m), systolic BP 123.6 ± 7.7vs128.6 ± 14.1 mmHg, fasting glucose 95.6 ± 19.4vs109.4 ± 43.7 mg/dl, cholesterol 175.5 ± 36.5vs186.4 ± 43.3 mg/dl, and triglycerides 147.6 ± 48.3vs159.5 ± 60.7 mg/dl (p < 0.01). Prevalence of metabolic syndrome declined in intervention group by 22.3%vs3.9%, p < 0.001).

Conclusion: An interactive voice response system based technology significantly reduced multiple cardiovascular risk factors and prevalence of metabolic syndrome.
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http://dx.doi.org/10.1016/j.dsx.2021.06.019DOI Listing
June 2021

Potential of nanoparticles encapsulated drugs for possible inhibition of the antimicrobial resistance development.

Biomed Pharmacother 2021 Sep 20;141:111943. Epub 2021 Jul 20.

Department of Laboratory Medicine, The Third Affiliated Hospital, Southern Medical University, No.183 West Zhongshan Avenue, Guangzhou, China. Electronic address:

The immune system is a dynamic network of cells and cytokines are the major mediators of immune responses which combat pathogens. Based on the cytokine production, effector T cells differentiate into subsets known as Th1, Th2, Th17, or Treg. This system serves as a barrier to intracellular pathogens, bacterial infections and stimulates the production of reactive oxygen species (ROS), reactive nitrogen intermediates, and nitric oxide, which diffuses across membranes and engulfs intracellular pathogens. Oxidative stress occurs when ROS, reactive nitrogen species (RNS) production, and antioxidant defences become imbalanced. Oxidative stress generated by infected cells produces a substantial amount of free radicals which enables the killing of intracellular pathogens. Intracellular pathogens are exposed to endogenous ROS as part of normal aerobic respiration, also exogenous ROS and RNS are generated by the host immune system in response to infection. Nanoparticles which are designed for drug delivery are capable of trapping the desired drug in the particles which protect the drug from enzymatic degradation in a biological system. The subcellular size of nanoparticles enables higher intracellular uptake of the drug which results in the reduction of the concentration of free drugs reducing their toxic effect. Research on the modulation of immune response and oxidative stress using nanoparticles used to encapsulate drugs has yet to be explored fully. In this review, we illustrate the immune activation and generation of oxidative stress properties which are mediated by nanoparticle encapsulated drug delivery systems which can make the therapy more effective in case of diseases caused by intracellular pathogens.
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http://dx.doi.org/10.1016/j.biopha.2021.111943DOI Listing
September 2021

Genotypic diversity of Mycobacterium tuberculosis isolates from North-Central Indian population.

Pathog Glob Health 2019 02 1;113(1):39-48. Epub 2019 Mar 1.

a Centre for Genomics, Molecular and Human Genetics , Jiwaji University , Gwalior , India.

Background: Different strains of Mycobacterium tuberculosis (MTB) are known to have different epidemiological and clinical characteristics. Some of them are widely distributed and associated with drug resistance, whereas others are locally predominated. Molecular epidemiological investigations have always been beneficial in identifying new strains and studying their transmission dynamics. Sahariya a primitive tribe of North Madhya Pradesh, India, has already been reported to have high prevalence of tuberculosis (TB) than their non-tribal neighbours. However, the information about MTB genotypes prevalent in Sahariya tribe and their non-tribal neighbours is not available.

Methods: A total of 214 clinical isolates representing Sahariya tribe and non-tribes were analyzed by spoligotyping and MIRU-VNTR typing.

Results: The EAI3_IND/SIT11 genotype was observed as major genotype in Sahariya tribe followed by CAS1_Delhi/SIT26 genotype. A 3.04 fold higher risk of getting TB with EAI3_IND/SIT11 genotype was observed in Sahariya as compared to the non-tribal population. The EAI_IND/SIT11 genotype also found to have more number of MDR-TB cases in Sahariya as well as true and possible transmission links. In Sahariya tribe, 3 clusters (6 isolates) reflected true transmission links, whereas 8 clusters consisted of 26 isolates revealed possible transmission links within the same geographical location or nearby houses.

Conclusion: The present study highlighted the predominance of EAI3_IND/SIT11 genotype in Sahariya tribe followed by CAS1_Delhi/SIT26 genotype. Combined approach of MIRU-VNTR typing and spoligotyping was observed more favourable in discrimination of MTB genotypes. Further, longitudinal studies using whole genome sequencing can provide more insights into genetic diversity, drug resistance and transmission dynamics of these prevalent genotypes.
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http://dx.doi.org/10.1080/20477724.2019.1583881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427501PMC
February 2019

Potential of adjunctive Mycobacterium w (MIP) immunotherapy in reducing the duration of standard chemotherapy against tuberculosis.

Indian J Tuberc 2018 Oct 6;65(4):335-344. Epub 2018 Sep 6.

Former Secretary, Department of Health Research, Govt of India and Director-General, Indian Council of Medical Research, Ansari Nagar, New Delhi, 110029, India. Electronic address:

Introduction: The need to shorten the treatment duration in tuberculosis has always been felt. Immunotherapy in combination with chemotherapy has been considered a promising approach for this purpose into tuberculosis. We studied the adjuvant immunotherapeutic activity of Mycobacterium indicus pranii (MIP or Mw) in combination with conventional chemotherapy using guinea pig of pulmonary tuberculosis infected with Mycobacterium tuberculosis H37Rv via aerosol.

Methods: Experimental animals treated with standard chemotherapy and immunotherapy (MIP) separately and in combination of both. Guinea pig lungs evaluated following infection and subsequent therapy at predefine time point. Various cytokine mRNA expressions levels were quantified by quantitative reverse transcriptase PCR at the 4th, 8th and 12th week post-infection of M. tuberculosis.

Results: We determined the time required for bacterial clearance from guinea pig lungs. Standard chemotherapy (RvCh) compared to the animals where chemotherapy plus Mw immunotherpay (RvChMwT) was given. It took 12 weeks to achieve bacterial clearance in the RvCh group while this was achieved in 8 weeks in RvChMwT group. Pro-inflammatory cytokines (IFN-γ, IL-2, IL-12p35 and TNF-α) level were higher in RvCh, RvChMwT and RvMwT group, while the IL-10 and TGF-β were suppressed.

Conclusion: Cytokine expression level showed that Mw in conjunction with chemotherapy enhances the effect of pro-inflammatory cytokines (such as, IFN-γ, IL-2, IL-12 and TNF-α) and reduces the production and effect of anti-inflammatory cytokines (like IL-10 and TGF-β) thereby restoring the pro-inflammatory / anti-inflammatory cytokines balance. Thus, the present study indicates that subject to rigorous testing by other parameters, Mw (MIP) as adjunct immunotherapy has potential for reducing treatment duration.
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http://dx.doi.org/10.1016/j.ijtb.2018.08.004DOI Listing
October 2018

Mapping of health research funding in India.

Natl Med J India 2017 Nov-Dec;30(6):309-316

Indian Council of Medical Research, Department of Health Research, Government of India, New Delhi, India.

Background.: We aimed to estimate the total annual funding available for health research in India. We also examined the trends of funding for health research since 2001 by major national and international agencies.

Methods.: We did a retrospective survey of 1150 health research institutions in India to estimate the quantum of funding over 5 years. We explored the Prowess database for industry spending on health research and development and gathered data from key funding agencies. All amounts were converted to 2015 constant US$.

Results.: The total health research funding available in India in 2011-12 was US$ 1.42 billion, 0.09% of the gross domestic product (GDP) including only 0.02% from public sources. The average annual increase of funding over the previous 5 years (2007-08 to 2011-12) was 8.8%. 95% of this funding was from Indian sources, including 79% by the Indian pharmaceutical industry. Of the total funding, only 3.2% was available for public health research. From 2006-10 to 2011-15 the funding for health research in India by the three major international agencies cumulatively decreased by 40.8%. The non-industry funding for non-communicable diseases doubled from 2007-08 to 2011-12, but the funding for some of the leading causes of disease burden, including neonatal disorders, cardiovascular disease, chronic respiratory disease, mental health, musculoskeletal disorders and injuries was substantially lower than their contribution to the disease burden.

Conclusion.: The total funding available for health research in India is lower than previous estimates, and only a miniscule proportion is available for public health research. The non industry funding for health research in India, which is predominantly from public resources, is extremely small, and had considerable mismatches with the major causes of disease burden. The magnitude of public funding for health research and its appropriate allocation should be addressed at the highest policy level.
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http://dx.doi.org/10.4103/0970-258X.239069DOI Listing
December 2018

Association of Toll like receptor 2 and 9 gene variants with pulmonary tuberculosis: exploration in a northern Indian population.

Mol Biol Rep 2018 Aug 19;45(4):469-476. Epub 2018 Apr 19.

Immunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (ICMR), Taj Ganj, Agra, 282004, India.

Tuberculosis (TB) is a disease of global importance. There is an increasing recognition of the role of Toll like receptors, important pattern recognition receptors of host immune system, in determining the susceptibility or resistance to TB in various populations. In an attempt to examine the importance of Toll like receptors in immune response to Mycobacterium tuberculosis infection, we explored two variants each of TLR2 and TLR9 in a population residing in Uttar Pradesh, India. Genotyping was performed to detect -196 to -174 del polymorphism and G2258A SNP (Arg753Gln, rs5743708) in TLR2 gene and -T1237C (rs5743836) and G2848A (rs352140) SNP in TLR9 gene in patients with pulmonary TB and healthy controls. The A allele of G2848A SNP in TLR9 gene was found with a marginally higher frequency among TB patients as compared to healthy controls, suggesting that A allele at position 2848 of TLR9 gene may be associated with susceptibility to TB in North Indian population [p = 0.05, Mantel-Haenszel OR = 1.34, 95% CI (1.0-1.82)].
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http://dx.doi.org/10.1007/s11033-018-4182-zDOI Listing
August 2018

Comparative study of genotypes of Mycobacterium tuberculosis from a Northern Indian setting with strains reported from other parts of India and neighboring countries.

Tuberculosis (Edinb) 2017 07 10;105:60-72. Epub 2017 Apr 10.

Former Secretary, Former Director General, Department of Health Research (Ministry of Health and Family Welfare), Indian Council of Medical Research, V. Ramalingaswami Bhawan, Ansari Nagar, Post Box 4911, New Delhi, 110 029, India. Electronic address:

This study was carried out to characterize Mycobacterium tuberculosis population in Ghatampur, Kanpur, North India, by spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTRs) typing. A total of 335 isolates were genotyped by spoligotyping and Central Asian (CAS) sub-lineage was the most prevalent, comprising 59.1% of all isolates. Other lineages were: East-African Indian (EAI) (19.10%), T (5.07%), Beijing (3.28%), Manu (2.98%), X (2.68%), S (0.89%), H3 (0.59%), Ural (0.59%), LAM 9 (0.29%) and unknown (5.37%). This data was compared with 8444 clinical isolates from other parts of India and neighboring countries. Thanks to interrogation of the SITVIT2 database, which shows that China is unique in having a predominance of Beijing lineage; Iran in having an almost equal proportion of Ural and CAS lineages; while the rest of the Middle-East and Indian subcontinent shows a gradient of CAS lineage predominating in the north of tropic of cancer, and the ancestral EAI lineage in South India and South-East Asia. Additionally, 12 loci MIRU-VNTR typing efficiently discriminated 13 spoligotype-defined clusters into 92 patterns; 53 isolates showed >70% homology. It was observed that Beijing lineage strains were more frequently associated with MDR strains (p-value = 0.001). A multi-step application of combination of spoligotyping and MIRU-VNTR typing for analyzing the molecular epidemiology of TB may provide a better means of fingerprinting and studying transmission dynamics.
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http://dx.doi.org/10.1016/j.tube.2017.04.003DOI Listing
July 2017

Genetic diversity & drug sensitivity profiles of isolates from two slums of Jaipur city, Rajasthan, India.

Indian J Med Res 2017 Jan;145(1):74-83

Department of Microbiology & Molecular Biology, National JALMA Institute for Leprosy & Other Mycobacterial Diseases, Agra; Former Secretary, Department of Health Research & Director-General, Indian Council of Medical Research, New Delhi, India.

Background & Objectives: Slums are considered as hotspots of tuberculosis (TB). The study of genetic diversity and drug susceptibility profile of Mycobacterium tuberculosis (MTB) will help understand the transmission dynamics and can be used for better prevention and control of the disease. The aim of this study was to determine the drug susceptibility profiles and genetic diversity using the random amplified polymorphic DNA (RAPD) and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU VNTR) of MTB isolates from sputum samples of pulmonary TB patients residing in the two slums of Jaipur city in Rajasthan, India.

Methods: Sputum samples collected from pulmonary TB patients, their contacts and suspects during 2010-2012 were processed for microscopy and mycobacterial culture. Drug susceptibility testing was done by one per cent indirect proportion method on Lowenstein-Jensen medium for first-line anti-TB drugs rifampicin, isoniazid, ethambutol and streptomycin. MTB DNA was extracted by physicochemical method, and DNA fingerprinting was done by RAPD and MIRU VNTR analysis.

Results: Among 175 sputum samples collected, 75 were positive (43.8%) for acid-fast bacilli, 83 for MTB culture and four were contaminated. Fifty two isolates (62.7%) were fully sensitive to four drugs, and five (6%) were multidrug resistant (MDR). RAPD analysis of 81 isolates revealed six clusters containing 23 (28.4%) isolates, and 58 (71.6%) were unique. MIRU VNTR analysis clustered 20 (24.7%) isolates, and 61 (75.3%) were unique.

Interpretation & Conclusions: About 62.7 per cent isolates from the sputum samples from slum areas were sensitive to four drugs; six per cent of isolates were MDR. Poly-resistance other than MDR was high (16%). About one-fourth isolates were clustered by either method. RAPD was rapid, less expensive but had low reproducibility. MIRU VNTR analysis could identify to greater extent the epidemiological link in the population studied.
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http://dx.doi.org/10.4103/ijmr.IJMR_336_14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460578PMC
January 2017

Assessing genetic diversity of Mycobacterium tuberculosis by spoligotyping and IS6110-based restriction fragment length polymorphism in North India.

Int J Mycobacteriol 2016 Dec 25;5 Suppl 1:S174-S175. Epub 2016 Nov 25.

Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Objective/background: Molecular epidemiology methods are very useful for differentiating between strains, assessing their diversity, and measuring the prevalence of the most circulating strain in an area. Various molecular typing methods using different molecular markers have been utilized worldwide, such as restriction fragment length polymorphism (RFLP), spoligotyping, Mycobacterial Interspersed Repetitive Unit - Variable Number of Tandem Repeat (MIRU-VNTR), and Double repetitive element-PCR (DRE-PCR) typing, for simultaneous detection and epidemiologic typing of Mycobacterium tuberculosis. The present study is conducted to assess the genetic diversity of M. tuberculosis by IS6110-RFLP and spoligotyping in patients attending a tertiary care hospital in eastern Uttar Pradesh, North India.

Methods: A total of 83 representative isolates of M. tuberculosis were included in this study. These isolates were subjected to spoligotyping and IS6110-RFLP DNA fingerprinting techniques as described previously.

Results: The spoligotype patterns were compared with SpolDB4.0; patterns of 64 out of 83 M. tuberculosis isolates were matched with the available data, while 19 isolates were found to be orphan, that is, absent in the SpolDB4.0 database. The majority of the M. tuberculosis strains (56.5%) belong to central Asian (32.5%), ill defined T (13.2%), and Beijing (10.8%) families. On IS6110-RFLP analysis, in 19.2% (16/83) of these isolates, IS6110 element was not found (0 copy number strains). Further, 15.6% (13/83) isolates were found to be low-copy-number strains having less than six copies of IS6110 element, and the remaining 65.0% (54/83) were multiple-copy-number strains with six or more copies of the element. On comparing the results of spoligotyping and IS-6110-RFLP, a total of 47 isolates were clustered by spoligotyping; out of these isolates, 40 were found to be unique by IS6110-RFLP.

Conclusion: Spoligotype analysis resulted in the grouping of a much larger number of isolates within apparently identical clusters compared with IS6110-RFLP typing, while IS6110-RFLP was not found to effectively distinguish between zero- and low-copy-number isolates. Therefore, we concluded that, in India, the use of both the techniques simultaneously for DNA fingerprinting of M. tuberculosis could be a better approach.
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http://dx.doi.org/10.1016/j.ijmyco.2016.11.015DOI Listing
December 2016

TlyA protein of Mycobacterium leprae: a probable bio-marker of active infection.

Lepr Rev 2016 Dec;87(4):501-15

The extent of pathogenicity of the mycobacterial infections depends on virulence factors that mediate survival inside macrophages. Virulence factors are generally believed to be specific for pathogenic species and mutated/non-functional in nonpathogenic strains. Mycobacterial TlyA can modulate the phagolysosome maturation pathway, immediately after entry into macrophages. Over-expression of open reading frame (ORF) ML1358 (tlyA) in tissues of leprosy patients by partial DNA chip and real time PCR analysis during active infection attracted our interest to explore the properties of this gene at molecular and serological levels, to understand its role in the host. Molecular properties were studied by cloning and expression of the corresponding gene in pASK-iba 43(þ) expression vector in E. coli and bioinformatics tools while sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and ELISA were applied to investigate the serological significance of rTlyA protein in different clinical states of leprosy. We observed that TlyA has a close relation among mycobacteria with specific protein domains in slow growing intracellular adapted pathogenic species. The presence of trans-membrane domains indicates its association to the cell membrane. The study revealed its highly significant sero-reactivity (P value , 0·001) in borderline lepromatous (BL) patients, and those with reversal reaction (RR) and erythema nodosum leprosum (ENL). Its role in active infection, association with the cell membrane, presence in pathogenic species and high sero-reactivity, suggested the tlyA gene as a strong disease progression marker.
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December 2016

Early detection of multidrug resistant (MDR) Mycobacterium tuberculosis in a single tube with in-house designed fluorescence resonance energy transfer (FRET) probes using real-time PCR.

Indian J Exp Biol 2016 Apr;54(4):229-36

Rapid and correct diagnosis is crucial for the management of multidrug resistance (MDR) in Mycobacterium tuberculosis (MTB). The present study aims at rapid diagnosis for identification of multidrug resistance tuberculosis (MDR-TB) using real-time PCR. FRET hybridization probes targeting most prominent four selected codons for rpoB526 and 531 and for katG314 and 315 genes were designed and evaluated on 143 clinical MTB isolates and paired sputa for rapid detection of MDR-TB. The results of real-time PCR were compared with gold standard L-J proportion method and further validated by DNA sequencing. Of the 143 MTB positive cultures, 85 and 58 isolates were found to be 'MDR' and 'pan susceptible', respectively by proportion L-J method. The sensitivity of real-time PCR for the detection of rifampicin (RIF) and isoniazid (INH) were 85.88 and 94.11%, respectively, and the specificity of method was found to be 98.27%. DNA sequencing of 31 MTB isolates having distinct melting temperature (Tm) as compared to the standard drug susceptible H37Rv strain showed 100% concordance with real-time PCR results. DNA sequencing revealed the mutations at Ser531Leu, His526Asp of rpoB gene and Ser315Thr, Thr314Pro of katG gene in RIF and INH resistance cases. This real-time PCR assay that targets limited number of loci in a selected range ensures direct and rapid detection of MDR-TB in Indian settings. However, future studies for revalidation as well as refinement are required to break the limitations of MDR-TB detection.
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April 2016

Scope of translational research focusing rural areas.

Indian J Med Res 2016 Jan;143(1):18-20

Department of Community Medicine, Dr. Rajendra Prasad Government Medical College, Kangra 176 001, Himachal Pradesh, India.

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http://dx.doi.org/10.4103/0971-5916.178579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822362PMC
January 2016

Mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events.

BMC Immunol 2015 Nov 9;16:67. Epub 2015 Nov 9.

Department of Immunology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (ICMR), Dr.M.Miyazaki Marg, Tajganj, Agra, 282001, India.

Background: Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB.

Methods: Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calcium mobilization in PBMCs of healthy individuals and TB patients by spectrofluorimetry, CD3 and CD28 induced activation of mitogen activated protein kinases (MAPKs) in PBMCs of healthy individuals and TB patients by western blotting and binding of transcription factors NFAT and NFκB by Electrophorectic mobility shift assay (EMSA).

Results: We observed CD3 triggered modulations in free intracellular calcium concentrations in PPD+ve healthy individuals and pulmonary TB patients after the treatment of M. tuberculosis antigens. As regards the downstream signalling events, phosphorylation of MAPKs, Extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 was curtailed by M. tuberculosis antigens in TB patients whereas, in PPD+ve healthy individuals only ERK1/2 phosphorylation was inhibited. Besides, the terminal signalling events like binding of transcription factors NFAT and NFκB was also altered by M. tuberculosis antigens. Altogether, our results suggest that M. tuberculosis antigens, specifically ESAT-6, interfere with TCR/CD28-induced upstream as well as downstream signalling events which might be responsible for defective IL-2 production which further contributed in T-cell unresponsiveness, implicated in the progression of disease.

Conclusion: To the best of our knowledge, this is the first study to investigate effect of Ag85A and ESAT-6 on TCR- and TCR/CD28- induced upstream and downstream signalling events of T-cell activation in TB patients. This study showed the effect of secretory antigens of M. tuberculosis in the modulation of T cell signalling pathways. This inflection is accomplished by altering the proximal and distal events of signalling cascade which could be involved in T-cell dysfunctioning during the progression of the disease.
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http://dx.doi.org/10.1186/s12865-015-0128-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640201PMC
November 2015

Consensus & Evidence-based INOSA Guidelines 2014 (First edition).

Indian J Chest Dis Allied Sci 2015 Jan-Mar;57(1):48-64

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive Sleep Apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or comorbidities or ≥ 15 such episodes without any sleep related symptoms or comorbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.
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October 2015

Consensus and evidence-based Indian initiative on obstructive sleep apnea guidelines 2014 (first edition).

Lung India 2015 Jul-Aug;32(4):422-34

Writing Committee of the Indian Initiative on Obstructive Sleep Apnoea Guidelines Working Group ; Indian Council of Medical Research, New Delhi, India.

Obstructive sleep apnea (OSA) and obstructive sleep apnea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences among the general public as well as the majority of primary care physicians across India is poor. This necessitated the development of the Indian initiative on obstructive sleep apnea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health and Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep-related symptoms or co-morbidities or ≥15 such episodes without any sleep-related symptoms or co-morbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents, and high-risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers, and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances (OA) are indicated for use in patients with mild to moderate OSA who prefer OA to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioral measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.
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http://dx.doi.org/10.4103/0970-2113.159677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502224PMC
July 2015

Recommendations for screening and early detection of common cancers in India.

Lancet Oncol 2015 Jul;16(7):e352-61

Institute of Cytology and Preventive Oncology, Noida, India.

Cancers of the breast, uterine cervix, and lip or oral cavity are three of the most common malignancies in India. Together, they account for about 34% of more than 1 million individuals diagnosed with cancer in India each year. At each of these cancer sites, tumours are detectable at early stages when they are most likely to be cured with standard treatment protocols. Recognising the key role that effective early detection and screening programmes could have in reducing the cancer burden, the Indian Institute for Cytology and Preventive Oncology, in collaboration with the US National Cancer Institute Center for Global Health, held a workshop to summarise feasible options and relevant evidence for screening and early detection of common cancers in India. The evidence-based recommendations provided in this Review are intended to act as a guide for policy makers, clinicians, and public health practitioners who are developing and implementing strategies in cancer control for the three most common cancers in India.
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http://dx.doi.org/10.1016/S1470-2045(15)00078-9DOI Listing
July 2015

Using implementation science to advance cancer prevention in India.

Asian Pac J Cancer Prev 2015 ;16(9):3639-44

Women's Global Health Imperative, RTI, San Francisco, USA E-mail :

Oral, cervical and breast cancers, which are either preventable and/or amenable to early detection and treatment, are the leading causes of cancer-related morbidity and mortality in India. In this paper, we describe implementation science research priorities to catalyze the prevention and control of these cancers in India. Research priorities were organized using a framework based on the implementation science literature and the World Health Organization's definition of health systems. They addressed both community-level as well as health systems-level issues. Community-level or "pull" priorities included the need to identify effective strategies to raise public awareness and understanding of cancer prevention, monitor knowledge levels, and address fear and stigma. Health systems-level or "push" and "infrastructure" priorities included dissemination of evidence- based practices, testing of point-of-care technologies for screening and diagnosis, identification of appropriate service delivery and financing models, and assessment of strategies to enhance the health workforce. Given the extent of available evidence, it is critical that cancer prevention and treatment efforts in India are accelerated. Implementation science research can generate critical insights and evidence to inform this acceleration.
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http://dx.doi.org/10.7314/apjcp.2015.16.9.3639DOI Listing
February 2016

Consensus & evidence-based INOSA Guidelines 2014 (first edition).

Indian J Med Res 2014 Sep;140(3):451-68

All India Institute of Medical Sciences

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive sleep apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or co-morbidities or ≥ 15 such episodes without any sleep related symptoms or co-morbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248396PMC
September 2014

Establishment of Biosafety Level-3 (BSL-3) laboratory: important criteria to consider while designing, constructing, commissioning & operating the facility in Indian setting.

Indian J Med Res 2014 Aug;140(2):171-83

Microbial Containment Complex, National Institute of Virology (ICMR), Pune, India.

Since the enactment of Environmental Protection Act in 1989 and Department of Biotechnology (DBT) guidelines to deal with genetically modified organisms, India has embarked on establishing various levels of biosafety laboratories to deal with highly infectious and pathogenic organisms. Occurrence of outbreaks due to rapidly spreading respiratory and haemorrhagic fever causing viruses has caused an urgency to create a safe laboratory environment. This has thus become a mandate, not only to protect laboratory workers, but also to protect the environment and community. In India, technology and science are progressing rapidly. Several BSL-3 [=high containment] laboratories are in the planning or execution phase, to tackle biosafety issues involved in handling highly infectious disease agents required for basic research and diagnosis. In most of the developing countries, the awareness about biocontainment has increased but planning, designing, constructing and operating BSL-3 laboratories need regular updates about the design and construction of facilities and clear definition of risk groups and their handling which should be in harmony with the latest international practices. This article describes the major steps involved in the process of construction of a BSL-3 laboratory in Indian settings, from freezing the concept of proposal to operationalization phase. The key to success of this kind of project is strong institutional commitment to biosafety norms, adequate fund availability, careful planning and designing, hiring good construction agency, monitoring by experienced consultancy agency and involvement of scientific and engineering personnel with biocontainment experience in the process.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216491PMC
August 2014

Proteomic analysis of Mycobacterium tuberculosis isolates resistant to kanamycin and amikacin.

J Proteomics 2013 Dec 12;94:68-77. Epub 2013 Sep 12.

Department of Biochemistry, National JALMA Institute for Leprosy & Other Mycobacterial Diseases (Indian Council of Medical Research), Dr. Matsuki Miyazaki Road, Tajganj, PO Box No-1101, Agra, PIN-282004 India.

Unlabelled: Kanamycin (KM) and amikacin (AK) are the key aminoglycoside drugs against tuberculosis (TB) and resistance to them severely affects the options for treatment. Many explanations have been proposed for drug resistance to these drugs but still some mechanisms are unknown. Proteins are the functional moiety of the cell and manifest in most of the biological processes; so, these are potential foci for the development of new therapeutics, diagnostics and vaccine. We examined the KM and AK resistant isolates of Mycobacterium tuberculosis using proteomic analysis comprising of two dimensional gel electrophoresis (2DGE), matrix assisted laser desorption ionization time-of-flight/time-of flight (MALDI-TOF/TOF) and bioinformatic tools like BLASTP, InterProScan, KEGG motif scan and molecular docking. Proteins intensities of twelve spots were found to be consistently increased in KM and AK resistant isolates and these were identified as Rv3867, Rv1932, Rv3418c, Rv1876, Rv2031c, Rv0155, Rv0643c, Rv3224, Rv0952, and Rv0440. Among these, Rv3867 and Rv3224 were identified as proteins with unknown function. All the proteins identified were cellular proteins. Molecular docking shows the proper interaction of both drugs with these molecules. Also, Rv1876 and Rv3224 were found to be probably involved in iron regulation/metabolism indicating the role of iron in imparting resistance to second line drugs.

Biological Significance: The study that was carried out shows that two dimensional electrophoresis along with mass spectrometry is still the best approach for proteomic analysis. To the best of our knowledge it is the first ever report on proteomic analysis of M. tuberculosis isolates resistant to second line drugs (kanamycin and amikacin). The major finding implicates that the genes/proteins involved in iron metabolism and the two hypothetical proteins (Rv3867 and Rv3224) might be playing some crucial role in contributing resistance to second line drugs. Further exploitation in this direction may lead to the development of newer therapeutics against tuberculosis.
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http://dx.doi.org/10.1016/j.jprot.2013.08.025DOI Listing
December 2013

Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases.

Lipids Health Dis 2012 Sep 17;11:119. Epub 2012 Sep 17.

Immunology Laboratory, National JALMA Institute for Leprosy and Other Mycobacterial Diseases-ICMR, Dr. M. Miyazaki Marg, Tajganj, Agra 282001, India.

Background: Advanced stages of leprosy show T cell unresponsiveness and lipids of mycobacterial origin are speculated to modulate immune responses in these patients. Present study elucidates the role of phenolicglycolipid (PGL-1) and Mannose-capped lipoarabinomannan (Man-LAM) on TCR- and TCR/CD28- mediated signalling.

Results: We observed that lipid antigens significantly inhibit proximal early signalling events like Zap-70 phosphorylation and calcium mobilization. Interestingly, these antigens preferentially curtailed TCR-triggered early downstream signalling events like p38 phosphorylation whereas potentiated that of Erk1/2. Further, at later stages inhibition of NFAT binding, IL-2 message, CD25 expression and T-cell blastogenesis by PGL-1 and Man-LAM was noted.

Conclusion: Altogether, we report that Man-LAM and PGL-1 preferentially interfere with TCR/CD28-triggered upstream cell signalling events, leading to reduced IL-2 secretion and T-cell blastogenesis which potentially could lead to immunosupression and thus, disease exacerbation, as noted in disease spectrum.
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http://dx.doi.org/10.1186/1476-511X-11-119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477116PMC
September 2012

Whole cell & culture filtrate proteins from prevalent genotypes of Mycobacterium tuberculosis provoke better antibody & T cell response than laboratory strain H 37 Rv.

Indian J Med Res 2012 May;135(5):745-55

Department of Immunology, National JALMA Institute for Leprosy & Other Mycobacterial Diseases (ICMR), Agra, India.

Background & Objectives: The immune responses to different antigens of Mycobacterium tuberculosis H 37 Rv vary from patient to patient with tuberculosis (TB). Therefore, significant difference might be documented between the H 37 Rv with long histories of passages and recent clinical isolates of M. tuberculosis. In the present study, immune response of TB patients and healthy controls against 39 clinical M. tuberculosis isolates was correlated with laboratory strain H 37 Rv.

Methods: The antibody response was studied coating whole cell extracts and culture filtrate proteins of M. tuberculosis isolates and laboratory strain H 37Rv by enzyme linked immunosorbent assay (ELISA). Lymphoproliferation was studied by incorporation of tritiated thymidine and cytokines (IFN-γ and IL-4) by using commercially available kits.

Results: Sero-reactivity to whole cell extract (WCE) of 11 clinical isolates was higher with pooled serum and individual's serum from tuberculosis patients showed significant reactivity (P<0.05) to ten of these isolates using ELISA. Of the WCE of 39 clinical isolates, 10 were found to be potent inducer of lymphoproliferation as well as cytokine secretion (P<0.05) in peripheral blood mononuclear cells from PPD+ healthy controls. Six culture filtrate proteins (CFPs) from these selected clinical isolates were also better inducers of antibody and T-cell response.

Interpretation & Conclusion: Overall, our results revealed that the clinical isolates belonging to prevalent genotypes; CAS1_Del (ST-26), East African-Indian (ST-11) and Beijing family (ST-1) induced better antibody and T cell responses compared to H 37 Rv laboratory strain. Further studies need to be done to purify and identify the dominant protein (s) using whole cell extract and culture filtrates from these immunologically relevant clinical M. tuberculosis isolates, which will be worthwhile to find out pathogenic factors, potential diagnostic markers and protective molecules for tuberculosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401709PMC
May 2012

Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry.

Mol Cell Proteomics 2011 Dec 3;10(12):M111.011627. Epub 2011 Oct 3.

Institute of Bioinformatics, International Technology Park, Bangalore, India.

The genome sequencing of H37Rv strain of Mycobacterium tuberculosis was completed in 1998 followed by the whole genome sequencing of a clinical isolate, CDC1551 in 2002. Since then, the genomic sequences of a number of other strains have become available making it one of the better studied pathogenic bacterial species at the genomic level. However, annotation of its genome remains challenging because of high GC content and dissimilarity to other model prokaryotes. To this end, we carried out an in-depth proteogenomic analysis of the M. tuberculosis H37Rv strain using Fourier transform mass spectrometry with high resolution at both MS and tandem MS levels. In all, we identified 3176 proteins from Mycobacterium tuberculosis representing ~80% of its total predicted gene count. In addition to protein database search, we carried out a genome database search, which led to identification of ~250 novel peptides. Based on these novel genome search-specific peptides, we discovered 41 novel protein coding genes in the H37Rv genome. Using peptide evidence and alternative gene prediction tools, we also corrected 79 gene models. Finally, mass spectrometric data from N terminus-derived peptides confirmed 727 existing annotations for translational start sites while correcting those for 33 proteins. We report creation of a high confidence set of protein coding regions in Mycobacterium tuberculosis genome obtained by high resolution tandem mass-spectrometry at both precursor and fragment detection steps for the first time. This proteogenomic approach should be generally applicable to other organisms whose genomes have already been sequenced for obtaining a more accurate catalogue of protein-coding genes.
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http://dx.doi.org/10.1074/mcp.M111.011445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275902PMC
December 2011

2D-QSAR model development and analysis on variant groups of anti-tuberculosis drugs.

Bioinformation 2011 6;7(2):82-90. Epub 2011 Sep 6.

A quantitative structure activity relationship study was performed on different groups of anti-tuberculosis drug compound for establishing quantitative relationship between biological activity and their physicochemical /structural properties. In recent years, a large number of herbal drugs are promoted in treatment of tuberculosis especially due to the emergence of MDR (multi drug resistance) and XDR (extensive drug resistance) tuberculosis. Multidrug-resistant TB (MDR-TB) is resistant to front-line drugs (isoniazid and rifampicin, the most powerful anti-TB drugs) and extensively drug-resistant TB (XDR-TB) is resistant to front-line and second-line drugs. The possibility of drug resistance TB increases when patient does not take prescribed drugs for defined time period. Natural products (secondary metabolites) isolated from the variety of sources including terrestrial and marine plants and animals, and microorganisms, have been recognized as having antituberculosis action and have recently been tested preclinically for their growth inhibitory activity towards Mycobacterium tuberculosis or related organisms. A quantitative structure activity relationship (QSAR) studies were performed to explore the antituberculosis compound from the derivatives of natural products . Theoretical results are in accord with the in vitro experimental data with reported growth inhibitory activity towards Mycobacterium tuberculosis or related organisms. Antitubercular activity was predicted through QSAR model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure of QSAR model was 74% (R(2) = 0.74) and predictive accuracy was 72% (RCV(2) = 0.72). QSAR studies indicate that dipole energy and heat of formation correlate well with anti-tubercular activity. These results could offer useful references for understanding mechanisms and directing the molecular design of new lead compounds with improved anti-tubercular activity. The generated QSAR model revealed the importance of structural, thermodynamic and electro topological parameters. The quantitative structure activity relationship provides important structural insight in designing of potent antitubercular agent.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174041PMC
http://dx.doi.org/10.6026/97320630007082DOI Listing
November 2011

Proteomic analysis of streptomycin resistant and sensitive clinical isolates of Mycobacterium tuberculosis.

Proteome Sci 2010 Nov 18;8:59. Epub 2010 Nov 18.

Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, PIN-282001, India.

Background: Streptomycin (SM) is a broad spectrum antibiotic and is an important component of any anti-tuberculosis therapy regimen. Several mechanisms have been proposed to explain the emergence of resistance but still our knowledge is inadequate. Proteins form a very complex network and drugs are countered by their modification/efflux or over expression/modification of targets. As proteins manifest most of the biological processes, these are attractive targets for developing drugs, immunodiagnostics or therapeutics. The aim of present study was to analyze and compare the protein profile of whole cell extracts from Mycobacterium tuberculosis clinical isolates susceptible and resistant to SM.

Results: Two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was employed for analyzing the protein profiles. Homology and in silico characterization for identified proteins was assessed using BLAST, InterProScan and KEGG database searches. Computational studies on the possible interactions between SM and identified proteins were carried out by a battery of online servers and softwares, namely, CLUSTALW (KEGG), I-TASSER, VMD, PatchDock and FireDock. On comparing 2DE patterns, nine proteins were found consistently overexpressed in SM resistant isolates and were identified as Rv0350, Rv0440, Rv1240, Rv3075c, Rv2971, Rv3028c, Rv2145c, Rv2031c and Rv0569. In silico docking analysis showed significant interactions of SM with essential (Rv0350, Rv0440 and Rv2971) and non essential (Rv1240, Rv3075c and Rv2031c) genes.

Conclusions: The computational results suggest high protein binding affinity of SM and suggested many possible interactions between identified proteins and the drug. Bioinformatic analysis proves attributive for analysis of diversity of proteins identified by whole proteome analysis. In-depth study of the these proteins will give an insight into probable sites of drug action other than established primary sites and hence may help in search of novel chemotherapeutic agents at these new sites as inhibitors.
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http://dx.doi.org/10.1186/1477-5956-8-59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998474PMC
November 2010

Streptomycin induced protein expression analysis in Mycobacterium tuberculosis by two-dimensional gel electrophoresis & mass spectrometry.

Indian J Med Res 2010 Oct;132:400-8

Department of Biochemistry, National JALMA Institute for Leprosy & Other Mycobacterial Diseases (ICMR), Agra, India.

Background & Objectives: The resistance of Mycobacterium tuberculosis to streptomycin, a core drug for treatment of category II tuberculosis (TB) has posed a major challenge to the health providers as well as research workers worldwide and has severely compromised the therapeutic options. A significant proportion of streptomycin resistant M. tuberculosis isolates failed to show mutations in conventional targets like rpsL and rrs. Although efflux, permeability, etc. are also known to contribute, yet a substantial proportion of isolates remains resistant suggesting involvement of other unknown mechanism. A resistant isolate may show altered gene as well as protein expression under drug induced conditions and a whole cell proteome analysis under induced conditions might help in further understanding the mechanisms of drug resistance. The present study was therefore designed with the objective to identify proteins related to streptomycin resistance in M. tuberculosis isolate grown in presence and absence of streptomycin (SM).

Methods: A clinical isolate of M. tuberculosis from Mycobacterial Repository Centre at the Institute (NJIL & OMD), Agra was grown in Sauton's medium for 36 h with/without subinhibitory concentration of the drug (2 μg/ml) and the cell lysate of isolates was prepared by sonication and centrifugation. Two-dimensional (2D) gel electrophoresis was employed to study the protein profile. The selected proteins were finally identified by MALDI-TOF mass spectrometry.

Results: Our study revealed eight inducible proteins (DnaK, fabG4, DNA-binding, hypothetical, two 14 kDa antigen and two 10 kDa chaperonin) that were upregulated in the presence of drug.

Interpretation & Conclusion: This preliminary study has thrown light on whether or not and how the resistant isolate responds to streptomycin at its non-toxic but sub-inhibitory concentration. An in-depth study of the upregulated proteins will give an insight into probable sites of drug action other than established primary sites.
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October 2010

The multifunctional PE_PGRS11 protein from Mycobacterium tuberculosis plays a role in regulating resistance to oxidative stress.

J Biol Chem 2010 Oct 17;285(40):30389-403. Epub 2010 Jun 17.

Department of Microbiology and Cell Biology, Supercomputer Education and Research Centre, Indian Institute of Science, Bangalore 560012, India.

Mycobacterium tuberculosis utilizes unique strategies to survive amid the hostile environment of infected host cells. Infection-specific expression of a unique mycobacterial cell surface antigen that could modulate key signaling cascades can act as a key survival strategy in curtailing host effector responses like oxidative stress. We demonstrate here that hypothetical PE_PGRS11 ORF encodes a functional phosphoglycerate mutase. The transcriptional analysis revealed that PE_PGRS11 is a hypoxia-responsive gene, and enforced expression of PE_PGRS11 by recombinant adenovirus or Mycobacterium smegmatis imparted resistance to alveolar epithelial cells against oxidative stress. PE_PGRS11-induced resistance to oxidative stress necessitated the modulation of genetic signatures like induced expression of Bcl2 or COX-2. This modulation of specific antiapoptotic molecular signatures involved recognition of PE_PGRS11 by TLR2 and subsequent activation of the PI3K-ERK1/2-NF-κB signaling axis. Furthermore, PE_PGRS11 markedly diminished H(2)O(2)-induced p38 MAPK activation. Interestingly, PE_PGRS11 protein was exposed at the mycobacterial cell surface and was involved in survival of mycobacteria under oxidative stress. Furthermore, PE_PGRS11 displayed differential B cell responses during tuberculosis infection. Taken together, our investigation identified PE_PGRS11 as an in vivo expressed immunodominant antigen that plays a crucial role in modulating cellular life span restrictions imposed during oxidative stress by triggering TLR2-dependent expression of COX-2 and Bcl2. These observations clearly provide a mechanistic basis for the rescue of pathogenic Mycobacterium-infected lung epithelial cells from oxidative stress.
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http://dx.doi.org/10.1074/jbc.M110.135251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945531PMC
October 2010

Microarray analysis of efflux pump genes in multidrug-resistant Mycobacterium tuberculosis during stress induced by common anti-tuberculous drugs.

Microb Drug Resist 2010 Mar;16(1):21-8

Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (NJILOMD), Agra, India.

Treatment of multidrug-resistant tuberculosis has become one of the major problems in public health. Understanding the molecular mechanisms of drug resistance has been central to tuberculosis research in recent times. DNA microarray technology provides the platform to study the genomic variations related to these mechanisms on a comprehensive level. To investigate the role of efflux pumps in drug resistance, we have constructed a custom DNA microarray containing 25 drug efflux pump genes of Mycobacterium tuberculosis (Indian Patent file no. 2071/DEL/2007) and monitored changes in the expression of these genes on exposure of common anti-tuberculous drugs. Expression profiling of efflux pump genes in multidrug-resistant M. tuberculosis isolates showed overexpression of 10 genes following exposure to various anti-tuberculous drugs. Although two of these genes (Rv3065 and Rv2938) have already been reported to be active drug efflux pumps in M. tuberculosis in earlier studies, the increased activities of other eight efflux pump genes (Rv1819, Rv2209, Rv2459, Rv2477c, Rv2688, Rv2846, Rv2994, and Rv3728) have been demonstrated in multidrug-resistant isolates by us for the first time. After confirmation of differential expressions of these genes by real-time reverse transcription polymerase chain reaction, it was observed that a simultaneous overexpression of efflux pump genes Rv2459, Rv3728, and Rv3065 was associated with resistance to the combination of isoniazid and ethambutol, and these drugs, along with streptomycin, were identified to group together, where efflux-mediated drug resistance appears to be important in M. tuberculosis and follows a constant pattern of induction in multidrug-resistant isolates. Isoniazid and ethambutol combination was also found to be affected in 10% (6/60) of the clinical isolates in the presence of carbonyl cyanide m-chloro phenylhydrazone in resazurin microtitre plate assay, supporting the role of efflux pumps in the resistance to these drugs. Overexpression of two of the genes (Rv2477 and Rv2209) has also been observed with ofloxacin stress in M. tuberculosis.
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http://dx.doi.org/10.1089/mdr.2009.0054DOI Listing
March 2010

Nocardial mycetoma: diverse clinical presentations.

Indian J Dermatol Venereol Leprol 2008 Nov-Dec;74(6):635-40

Department of Dermatology, Venereology and Leprosy, Indira Gandhi Medical College, Shimla, India.

Nocardia spp are gram-positive, aerobic, acid-fast bacteria which exist as saprophytes in nature. Invasive disseminated infections are particularly common in immunocompromised or debilitated hosts. Superficial infections with Nocardia spp occur as a result of local trauma and contamination of the wound. Clinically, it presents as acute infection (abscesses or cellulitis), mycetoma, or sporotrichoid infection. Differential diagnosis includes eumycetoma, chromomycosis, blastomycosis, coccidioidomycosis, sporotrichosis, tuberculosis, botryomycosis, syphilis, yaws, and neoplasia. Its diagnosis is confirmed by demonstrating the causative organism in exudates (as granules), tissue specimens, or cultures. Early diagnosis will obviate need for drastic surgical measures as early institution of chemotherapy is effective in most patients. However, its diagnosis is often delayed due to diverse clinical presentations and for want of clinical suspicion, particularly in non-endemic areas. This paper presents 4 clinical forms of this not so uncommon disease, emphasizing the importance of high index of clinical suspicion, especially in non-endemic regions; and the significance of repeated examination of exudates for Nocardia granules for an early diagnosis.
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http://dx.doi.org/10.4103/0378-6323.45110DOI Listing
November 2009
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