Publications by authors named "Alireza Neshani"

11 Publications

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Synergistic effect of two antimicrobial peptides, Nisin and P10 with conventional antibiotics against extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates.

Microb Pathog 2021 Jan 17;150:104700. Epub 2020 Dec 17.

Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Infections caused by drug-resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa are now a global problem that requires the immediate development of new antimicrobial drugs. Combination therapy and using antimicrobial peptides are two strategies with high potential to solve this issue. By these strategies, this study aimed to determine the antimicrobial effect of Nisin and P10 antimicrobial peptides on extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates, and investigate the most effective combination of an antimicrobial peptide with an antibiotic.

Material And Methods: This study was performed on five resistant clinical isolates and one standard strain for each kind of bacterium. First, the minimum inhibitory concentrations of two antimicrobial peptides (Nisin and P10) and five common antibiotics for the treatment of Gram-negative bacteria (ceftazidime, tobramycin, ciprofloxacin, doripenem, and colistin) was determined using Scanner-Assisted Colorimetric MIC Method. Then, the combination effect of P10+Nisin, P10+antibiotics, Nisin + antibiotics was investigated using checkerboard method.

Results: The MIC value of Nisin and P10 against studied pathogens were 64-256 and 8-32 μg/ml, respectively. P10+Nisin combination showed synergistic effect against standard strains and additive effect against drug-resistant clinical isolates. It was also found that the combination effect of P10+ceftazidim, P10+doripenem, and Nisin + colistin was synergistic in most cases. Nisin + tobramycin combination showed synergistic effect in exposure to standard strains, while the synergy is strain-dependent against drug-resistant clinical isolates.

Conclusion: In conclusion, the synergism of Nisin + colistin and P10+ceftazidime/doripenem could be of great therapeutic value as antimicrobial drugs against infections caused by colistin-resistant P.aeruginosa and XDR A. baumannii.
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http://dx.doi.org/10.1016/j.micpath.2020.104700DOI Listing
January 2021

Nanotechnology-driven advances in the treatment of diabetic wounds.

Biotechnol Appl Biochem 2020 Oct 12. Epub 2020 Oct 12.

Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Diabetic foot ulcers (DFUs) are chronic severe complications of diabetes disease and remain a worldwide clinical challenge with social and economic consequences. Diabetic wounds can cause infection, amputation of lower extremities, and even death. Several factors including impaired angiogenesis, vascular insufficiency, and bacterial infections result in a delayed process of wound healing in diabetic patients. Treatment of wound infections using traditional antibiotics has become a critical status. Thus, finding new therapeutic strategies to manage diabetic wounds is urgently needed. Nanotechnology has emerged as an efficient approach for this purpose. This review aimed to summarize recent advances using nanotechnology for the treatment of diabetic wounds.
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http://dx.doi.org/10.1002/bab.2051DOI Listing
October 2020

COVID-19 target: A specific target for novel coronavirus detection.

Gene Rep 2020 Sep 30;20:100740. Epub 2020 May 30.

Antimicrobial Resistance Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.

An ongoing outbreak of pneumonia associated with a novel coronavirus has been reported worldwide and become a global health problem; hence, the diagnosis and differentiation of this virus from other types of coronavirus is essential to control of the disease. To this end, the analysis of genomics data plays a vital role in introducing a stronger target and consequently provides better results in laboratory examinations. The modified comparative genomics approach helps us to find novel specific targets by comparing two or more sequences on the nucleotide collection database. We, for the first time, detected ORF8 gene as a potential target for the detection of the novel coronavirus. Unlike previous reported genes (RdRP, E and N genes), ORF8 is entirely specific to the novel coronavirus (COVID-19) and has no cross-reactivity with other kinds of coronavirus. Accordingly, ORF8 gene can be used as an additional confirmatory assay.
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http://dx.doi.org/10.1016/j.genrep.2020.100740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261075PMC
September 2020

Construction, Cloning, and Expression of CagA Recombinant Protein of .

Avicenna J Med Biotechnol 2020 Apr-Jun;12(2):135-138

Department of Microbiology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: This study aimed to assess construction and expression of CagA recombinant protein of in BL21.

Methods: Bioinformatics was used in designing the desired gene by Gene Runner. Next, the construct was subcloned to pET21b vector and this process was confirmed by Polymerase Chain Reaction (PCR), enzyme digestion and sequencing techniques. Then, it was cloned in the Escherichia coli BL21 as an expression host. Expression of protein was verified using sodium dodecyl sulfate- polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting technique. For purification of the protein, the Ni-NTA column was used. Protein concentration was determined by the Bicinchoninic Acid Protein Assay Kit (Parstoos). Finally, Western blotting was performed using CagA antibodies and normal human serum for determining immunogenicity feature with human antiserum.

Results: According to the results of the present study, CagA construct was cloned into the pET21b vector and after confirmation and cloning in host expression, recombinant protein with the size of 38 was successfully expressed and purified. The recombinant CagA protein showed immunogenicity characteristics with human antiserum.

Conclusion: In conclusion, only 5'-end of recombinant protein CagA with high immunogenicity effects was successfully constructed, cloned and expressed. Also, CagA recombinant protein showed good immunogenicity activity with human antiserum.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229452PMC
May 2020

Antimicrobial peptides as a promising treatment option against Acinetobacter baumannii infections.

Microb Pathog 2020 Sep 5;146:104238. Epub 2020 May 5.

Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

Background: With the increasing rate of antibiotic resistance in Acinetobacter, the World Health Organization introduced the carbapenem-resistant isolates in the priority pathogens list for which innovative new treatments are urgently needed. Antimicrobial peptides (AMPs) are one of the antimicrobial agents with high potential to produce new anti-Acinetobacter drugs. This review aims to summarize recent advances and compare AMPs with anti-Acinetobacter baumannii activity.

Methods: Active AMPs against Acinetobacter were considered, and essential features, including structure, mechanism of action, anti-A. baumannii potent, and other prominent characteristics, were investigated and compared to each other. In this regard, the Google Scholar search engine and databases of PubMed, Scopus, and Web of Science were used.

Results: Forty-six anti-Acinetobacter peptides were identified and classified into ten groups: Cathelicidins, Defensins, Frog AMPs, Melittin, Cecropins, Mastoparan, Histatins, Dermcidins, Tachyplesins, and computationally designed AMPs. According to the Minimum Inhibitory Concentration (MIC) reports, six peptides of Melittin, Histatin-8, Omega76, AM-CATH36, Hymenochirin, and Mastoparan have the highest anti-A. baumannii power against sensitive and antibiotic-resistant isolates. All anti-Acinetobacter peptides except Dermcidin have a net positive charge. Most of these peptides have alpha-helical structure; however, β-sheet and other structures have been observed among them. The mechanism of action of these antimicrobial agents is divided into two categories of membrane-based and intracellular target-based attack.

Conclusion: Evidence from this review indicates that AMPs would be likely among the main anti-A. baumannii drugs in the post-antibiotic era. Also, the application of computer science to increase anti-A. baumannii activity and reduce toxicity could be helpful.
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http://dx.doi.org/10.1016/j.micpath.2020.104238DOI Listing
September 2020

Pulmonary Nocardiosis in Suspected Tuberculosis Patients: A Systematic Review and Meta-Analysis of Cross-Sectional Studies.

Ethiop J Health Sci 2020 Mar;30(2):293-300

Infectious Diseases Research Center, Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

Background: nocardiosis is an opportunistic infectious disease in immunocompromised patients. The most common form of nocardiosis infection in humans is pulmonary nocrdiosis caused by inhaling Nocardia species from the environment. Thus, this study aimed to evaluate the pulmonary nocardiosis in patients with suspected tuberculosis using systematic review and meta-analysis.

Methods: We conducted a systematic search for cross-sectional studies focused on the pulmonary nocardiosis among patients with pulmonary tuberculosis based on the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) published from January 2001 to October 2019. The search was conducted in MEDLINE/PubMed, Web of Science, Scopus, Cochrane Library, Google Scholar, Science Direct databases, and Iranian databases. Medical subject headings (MeSH) and text words were searched: "pulmonary nocardiosis", "nocardiosis", OR "nocardial infection", "pulmonary nocardial infections/agents", AND "pulmonary tuberculosis", OR "pulmonary TB", AND "Iran". Two of the reviewers enrolled independently articles published in English and Persian languages according to the inclusion and the exclusion criteria. Comprehensive Meta-Analysis software (Version 3.3.070) was used for meta-analysis.

Results: Only 4 studies met the eligibility criteria. The pulmonary nocardiosis prevalence varied from 1.7% to 6.7%. The combined prevalence of nocardiosis among patients with suspected pulmonary tuberculosis in Iran was 4.8% (95% CI: 3-7.3, Q=5.8, Z=12.7). No heterogeneity was observed between studies because I was 48.3. N. cyriacigeorgica and N. asteroides were reported as the prevalent isolates, respectively.

Conclusions: This review showed in patients suspected TB when they were negative in all diagnosis laboratory tests, nocardiosis cases which be considered.
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http://dx.doi.org/10.4314/ejhs.v30i2.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060384PMC
March 2020

Epinecidin-1, a highly potent marine antimicrobial peptide with anticancer and immunomodulatory activities.

BMC Pharmacol Toxicol 2019 05 28;20(1):33. Epub 2019 May 28.

Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Antibiotic-resistant pathogens are an emerging threat in this century. Epinecidin-1 is a multi-functional Antimicrobial Peptide (AMP) produced by Orange-spotted grouper (Epinephelus coioides) has been shown to have extensive potentials as an alternative for current antibiotics. Due to the huge costs for the study and the production of a new drug, if an antimicrobial peptide has other beneficial functions in addition to antimicrobial activities, it would be preferred.

Methods: In this study, properties and applications of Epinecidin-1 were investigated and addressed comprehensively. To achieve this, the Google Scholar search engine and three databases of PubMed, Scopus, and Web of Science were used.

Results: Epinecidin-1 is a cationic AMP with an alpha-helical structure. Seven functional usages of this peptide have been reported in the literature including antibacterial, antifungal, antiviral, antiprotozoal, anticancer, immunomodulatory, and wound healing properties. Moreover, this peptide has high potential to be used as an active ingredient in cleaning solutions as well as application in vaccine production.

Conclusion: Due to significant antimicrobial activities tested on bacteria such as Staphylococcus aureus and Helicobacter pylori and also wound healing properties, Epi-1 has high potential to be considered as an important candidate for the production of new drugs and treatment of various infections including diabetic foot ulcer and peptic ulcer. Moreover, adjuvant-like properties of Epi-1 make it a suitable candidate for the studies related to an adjuvant. Other attractive properties such as anticancer effects have also been reported for this peptide which encourages further studies on this peptide.
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http://dx.doi.org/10.1186/s40360-019-0309-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537373PMC
May 2019

The short-chain dehydrogenases/reductases (SDR) gene: A new specific target for rapid detection of Mycobacterium tuberculosis complex by modified comparative genomic analysis.

Infect Genet Evol 2019 06 12;70:158-164. Epub 2019 Jan 12.

Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Early detection of tuberculosis is one of the crucial steps for TB control. Although, the sensitivity of conventional methods like Lowenstein Jensen (LJ) culture and direct staining is quite low, molecular techniques like polymerase chain reaction (PCR) are more sensitive and be considered as useful tools for rapid detection of tuberculosis. Various genes like IS6110 and mpb64 have been used as target for detection of M. tuberculosis, but more research is needed to find the most specific targets. The short-chain dehydrogenases/reductases family (SDR) is one of a very large family of NAD- or NADP-dependent oxidoreductase enzymes which is present in all M. tuberculosis strains. The large part of SDR sequences in tuberculosis is completely conserved and different from non-tuberculosis mycobacterium. The aim of the study was to develop an in-house PCR assay using the SDR target for rapid detection of M. tuberculosis from clinical specimens.

Method: M. tuberculosis-specific sequences were found using modified genome comparison method and the primers were designed by the Primer Premier 5.0 software. A PCR assay was developed targeting the nucleotide sequences within the SDR gene. A total of 50 cultivated specimens and 120 clinical specimens were evaluated by PCR.

Results: The clinical evaluation of SDR PCR assay showed high specificity (100%) and high sensitivity (88.5%). The analytical sensitivity was 10 fg of template DNA which is theoretically equivalent to 2 copy of genomic DNA per microliter. The SDR is a new specific target of M. tuberculosis and no cross-reactivity was observed to non-tuberculosis mycobacterium and other pathogenic bacteria.

Conclusions: Based on our results, the SDR gene can be considered as a useful target for detection of M. tuberculosis complex from clinical specimens.
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http://dx.doi.org/10.1016/j.meegid.2019.01.012DOI Listing
June 2019

Review of antimicrobial peptides with anti-Helicobacter pylori activity.

Helicobacter 2019 Feb 15;24(1):e12555. Epub 2018 Nov 15.

Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: The emergence of antibiotic-resistant Helicobacter pylori strains in recent years has increased the need for finding an alternative in the post-antibiotic era. One of the fields being considered for this purpose is antimicrobial peptides. The aim of this review was to provide an obvious scheme from the studied anti-H. pylori peptides and to investigate their common features.

Method: First, all of the antimicrobial peptides with their anti-H. pylori effects have been proved up to September 2018 were selected and their information including structure, mechanism of action, and function was reviewed. To achieve this, three databases of PubMed, Scopus, and Web of science were used.

Results: A total of 9 groups containing 22 antimicrobial peptides were found with demonstrated anti-H. pylori effects. The nine groups included pexiganan, tilapia piscidins, epinecidin-1, cathelicidins, defensins, bicarinalin, odorranain-HP, PGLa-AM1, and bacteriocins. Most of the antimicrobial peptides, not all, had common features such as the ability to kill antibiotic-resistant strains, having α-helical structure, being cationic, with high positive charge and isoelectric point.

Conclusion: Antimicrobial peptides with anti-H. pylori effects have the potential to replace the antibiotics, especially in the post-antibiotic era, if a rapid and low-cost production method would be found.
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http://dx.doi.org/10.1111/hel.12555DOI Listing
February 2019

Modified genome comparison method: a new approach for identification of specific targets in molecular diagnostic tests using Mycobacterium tuberculosis complex as an example.

BMC Infect Dis 2018 Oct 12;18(1):517. Epub 2018 Oct 12.

Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: The first step of designing any genome-based molecular diagnostic test is to find a specific target sequence. The modified genome comparison method is one of the easiest and most comprehensive ways to achieve this goal. In this study, we aimed to explain this method with the example of Mycobacterium tuberculosis complex and investigate its efficacy in a diagnostic test.

Methods: A specific target was identified using modified genome comparison method and an in-house PCR test was designed. To determine the analytical sensitivity and specificity, 10 standard specimens were used. Also, 230 specimens were used to determine the clinical sensitivity and specificity.

Results: The identity and query cover of our new diagnostic target (5KST) were ≥ 90% with M. tuberculosis complex. The 5KST-PCR sensitivity was 100% for smear-positive, culture-positive and 85.7% for smear-negative, culture-positive specimens. All of 100 smear-negative, culture-negative specimens were negative in 5KST-PCR (100% clinical specificity). Analytical sensitivity of 5KST-PCR was approximately 1 copy of genomic DNA per microliter.

Conclusions: Modified genome comparison method is a confident way to find specific targets for use in diagnostic tests. Accordingly, the 5KST-PCR designed in this study has high sensitivity and specificity and can be replaced for conventional TB PCR tests.
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http://dx.doi.org/10.1186/s12879-018-3417-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186143PMC
October 2018

Potent and selective inhibitors of class A β-lactamase: 7-prenyloxy coumarins.

J Antibiot (Tokyo) 2014 May 12;67(5):373-7. Epub 2014 Feb 12.

1] Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran [2] Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Class A and D β-lactamases are the main causes of resistance against β-lactam antibiotics, especially the penam group, in Staphylococcus aureus. On the basis of the potentiator property of ethanolic extracts of Ferula szowitsiana root on penicillin, MIC values observed for resistant S. aureus, the main naturally occurring compounds in these extracts, auraptene, umbelliprenin and galbanic acid, were evaluated for β-lactamase inhibitory activity. Amongst them auraptene showed the most potent inhibitory activity (IC50=21±1.5 μM) toward class A β-lactamase, whereas no inhibition was observed for class D β-lactamase. To obtain the structure activity relationship of the mentioned compounds and rationalize the enzyme inhibitory results, docking analysis was performed for both groups of β-lactamases. Docking analysis showed that the compounds have 100-500-fold lower bonding affinity toward the class D β-lactamase than toward the class A enzyme.
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http://dx.doi.org/10.1038/ja.2014.9DOI Listing
May 2014