Publications by authors named "Héctor Alex Saka"

10 Publications

  • Page 1 of 1

Detection of Vibrio cholerae aDNA in human burials from the fifth cholera pandemic in Argentina (1886-1887 AD).

Int J Paleopathol 2021 Mar 13;32:74-79. Epub 2021 Jan 13.

Instituto de Antropología de Córdoba (IDACOR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba (UNC), Departamento de Antropología, Facultad de Filosofía y Humanidades, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina. Electronic address:

Objective: Detecting traces of ancient DNA of Vibrio cholerae to provide genetic information associated with the fifth cholera pandemic.

Materials: Sediment samples from the sacral foramina of four individuals were analyzed, recovered from a mass grave near an institution dedicated exclusively to the isolation and treatment of citizens infected with cholera in the late 19th century in the city of Cordoba, Argentina.

Methods: Paleogenetic techniques (ancient DNA extraction, PCR amplification, and Sanger sequencing) were applied. Specific primers for Vibrio cholerae (VCR, ctxA, ctxB, and tcpA) were designed.

Results: By amplifying and sequencing the Vibrio cholerae repeats fragment, the infection in at least one individual was confirmed.

Conclusions: The synthesis of the paleogenetic results with the archaeological and historical evidence strongly supports that at least one individual from the mass grave in Cordoba, Argentina, was a victim of the fifth cholera pandemic.

Significance: Confirming the presence of the disease through multiple lines of evidence, including genetic, archaeological, and historical analyses, strengthens and affirms our understanding of the presence, effects, and potential evolutionary paths of the disease in the past.

Limitations: Vibrio cholerae repeats were sequenced in one individual, while the remaining genes could not be amplified, which is likely related to gene copy number.

Suggestions For Future Research: Paleogenetic examination of ancient samples from different locations will broaden our understanding of the origin, evolution, and past dissemination of Vibrio cholerae epidemic strains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpp.2020.12.004DOI Listing
March 2021

[Clinical, epidemiological and microbiological characterization of bacteremia produced by carbapenem-resistant enterobacteria in a university hospital in Córdoba, Argentina].

Rev Chilena Infectol 2020 Aug;37(4):362-370

Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.

Background: Enterobacteriaceae are a major cause of bloodstream infections and their antimicrobial resistance continues to increase. This leads to higher morbidity-mortality rates and public health costs. Carbapenem-resistant Enterobacteriaceae represent a serious challenge globally, since there are few therapeutic options available.

Aim: Clinical/microbiological characterization of the carbapenem-resistant bacteremia observed over a period of 4 years.

Methods: Retrospective, observational and descriptive study about bacteremia caused by carbapenem-resistant and susceptible Enterobacteriaceae.

Results: A total of 84 patients with bacteremia including carbapenem-resistant and susceptible Enterobacteriaceae were analyzed. We found that patients infected with carbapenem-resistant strains presented a higher proportion of: previous antibiotic treatment, hospitalization in intensive care unit (ICU), onset of the bacteremia during hospitalization in ICU and previous infection with extended-spectrum-beta-lactamase producing Enterobacteriaceae. Additionally, we observed a predominance of KPC-producing Klebsiella pneumoniae and an attributable mortality rate of 52.4%.

Discussion: This study allowed for a better understanding of an emerging problem with high mortality, which in turn is useful for the design and adoption of infection control strategies and effective treatment regimens adapted to our local epidemiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4067/S0716-10182020000400362DOI Listing
August 2020

Persistence: A Survival Strategy to Evade Antimicrobial Effects and .

Front Microbiol 2018 12;9:3101. Epub 2018 Dec 12.

CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.

The comprise a group of highly adapted bacterial pathogens sharing a unique intracellular lifestyle. Three species are pathogenic to humans: , and . is the leading bacterial cause of sexually-transmitted infections and infectious blindness worldwide. is a major cause of community-acquired atypical pneumonia. primarily affects psittacine birds and can be transmitted to humans causing psittacosis, a potentially fatal form of pneumonia. As opposed to other bacterial pathogens, the spread of clinically relevant antimicrobial resistance genes does not seem to be a major problem for the treatment of infections. However, when exposed to stressing conditions, like those arising from exposure to antimicrobial stimuli, these bacteria undergo a temporary interruption in their replication cycle and enter a viable but non-cultivable state known as persistence. When the stressing conditions are removed, resumes replication and generation of infectious particles. This review gives an overview of the different survival strategies used by to evade the deleterious effects of penicillin and IFNγ, with a focus on the different models used to study persistence, their contribution to elucidating the molecular basis of this complex phenomenon and their potential implications for studies in animal models of infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2018.03101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299033PMC
December 2018

Male genital tract immune response against infection.

Reproduction 2017 10;154(4):R99-R110

Centro de Investigaciones en Bioquímica Clínica e Inmunología CIBICI-CONICETDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina

is the most commonly reported agent of sexually transmitted bacterial infections worldwide. This pathogen frequently leads to persistent, long-term, subclinical infections, which in turn may cause severe pathology in susceptible hosts. This is in part due to the strategies that uses to survive within epithelial cells and to evade the host immune response, such as subverting intracellular trafficking, interfering signaling pathways and preventing apoptosis. Innate immune receptors such as toll-like receptors expressed on epithelial and immune cells in the genital tract mediate the recognition of chlamydial molecular patterns. After bacterial recognition, a subset of pro-inflammatory cytokines and chemokines are continuously released by epithelial cells. The innate immune response is followed by the initiation of the adaptive response against , which in turn may result in T helper 1-mediated protection or in T helper 2-mediated immunopathology. Understanding the molecular mechanisms developed by to avoid killing and host immune response would be crucial for designing new therapeutic approaches and developing protective vaccines. In this review, we focus on chlamydial survival strategies and the elicited immune responses in male genital tract infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/REP-16-0561DOI Listing
October 2017

Chlamydia trachomatis Infection Leads to Defined Alterations to the Lipid Droplet Proteome in Epithelial Cells.

PLoS One 2015 24;10(4):e0124630. Epub 2015 Apr 24.

Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina, United States of America.

The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and a main cause of genital and ocular diseases. During its intracellular cycle, C. trachomatis replicates inside a membrane-bound vacuole termed an "inclusion". Acquisition of lipids (and other nutrients) from the host cell is a critical step in chlamydial replication. Lipid droplets (LD) are ubiquitous, ER-derived neutral lipid-rich storage organelles surrounded by a phospholipids monolayer and associated proteins. Previous studies have shown that LDs accumulate at the periphery of, and eventually translocate into, the chlamydial inclusion. These observations point out to Chlamydia-mediated manipulation of LDs in infected cells, which may impact the function and thereby the protein composition of these organelles. By means of a label-free quantitative mass spectrometry approach we found that the LD proteome is modified in the context of C. trachomatis infection. We determined that LDs isolated from C. trachomatis-infected cells were enriched in proteins related to lipid metabolism, biosynthesis and LD-specific functions. Interestingly, consistent with the observation that LDs intimately associate with the inclusion, a subset of inclusion membrane proteins co-purified with LD protein extracts. Finally, genetic ablation of LDs negatively affected generation of C. trachomatis infectious progeny, consistent with a role for LD biogenesis in optimal chlamydial growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124630PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409204PMC
January 2016

Emerging roles for lipid droplets in immunity and host-pathogen interactions.

Annu Rev Cell Dev Biol 2012 11;28:411-37. Epub 2012 May 11.

Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina 27710, USA.

Lipid droplets (LDs) are neutral lipid storage organelles ubiquitous to eukaryotic cells. It is increasingly recognized that LDs interact extensively with other organelles and that they perform functions beyond passive lipid storage and lipid homeostasis. One emerging function for LDs is the coordination of immune responses, as these organelles participate in the generation of prostaglandins and leukotrienes, which are important inflammation mediators. Similarly, LDs are also beginning to be recognized as playing a role in interferon responses and in antigen cross presentation. Not surprisingly, there is emerging evidence that many pathogens, including hepatitis C and Dengue viruses, Chlamydia, and Mycobacterium, target LDs during infection either for nutritional purposes or as part of an anti-immunity strategy. We here review recent findings that link LDs to the regulation and execution of immune responses in the context of host-pathogen interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-cellbio-092910-153958DOI Listing
March 2013

Acquisition of nutrients by Chlamydiae: unique challenges of living in an intracellular compartment.

Curr Opin Microbiol 2010 Feb 16;13(1):4-10. Epub 2009 Dec 16.

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.

The Chlamydiae are obligate intracellular pathogens that replicate within a membrane-bound vacuole, termed the 'inclusion'. From this compartment, bacteria acquire essential nutrients by selectively redirecting transport vesicles and hijacking intracellular organelles. Rerouting is achieved by several mechanisms including proteolysis-mediated fragmentation of the Golgi apparatus, recruitment of Rab GTPases and SNAREs, and translocation of cytoplasmic organelles into the inclusion lumen. Given Chlamydiae's extended coevolution with eukaryotic cells, it is likely that co-option of multiple cellular pathways is a strategy to provide redundancy in the acquisition of essential nutrients from the host and has contributed to the success of these highly adapted pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mib.2009.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202608PMC
February 2010

Vibrio cholerae cytolysin is essential for high enterotoxicity and apoptosis induction produced by a cholera toxin gene-negative V. cholerae non-O1, non-O139 strain.

Microb Pathog 2008 Feb 31;44(2):118-28. Epub 2007 Aug 31.

Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Centro de Investigaciones en Bioquímica e Inmunología ClBICI-CONICET, Córdoba, Argentina.

Cholera toxin (CT) gene-negative Vibrio cholerae non-O1, non-O139 strains may cause severe diarrhea though their pathogenic mechanism remains unclear. V. cholerae cytolysin (VCC) is a pore-forming exotoxin encoded in the hlyA gene of V. cholerae whose contribution to the pathogenesis is not fully understood. In this work, the virulence properties of a CT gene-negative V. cholerae non-O1, non-O139 strain causing a cholera-like syndrome were analyzed. Inoculation of rabbit ileal loops with the wild type strain induced extensive fluid accumulation, accompanied by severe histopathological damage characterized by villus shortening, lymphangiectasia and focal areas of necrosis. These pathogenic effects were abrogated by mutation of the hlyA gene thus pointing out the main role of VCC in the virulence of the strain. Interestingly, this toxin was capable of triggering apoptosis in human intestinal cell lines due to its anion channel activity. Moreover, the wild type strain also induced increased apoptosis of the intestinal epithelium cells which was not observed upon inoculation of the VCC null mutant strain, indicating that VCC may trigger apoptotic cell death during infection in vivo. Altogether, these results support a main role of VCC in the pathogenesis of the CT gene-negative V. cholerae non-O1, non-O139 strain and identify apoptosis as a previously unrecognized cell death pathway triggered by VCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micpath.2007.08.013DOI Listing
February 2008

Protective role of autophagy against Vibrio cholerae cytolysin, a pore-forming toxin from V. cholerae.

Proc Natl Acad Sci U S A 2007 Feb 31;104(6):1829-34. Epub 2007 Jan 31.

Laboratorio de Biología Celular y Molecular, Instituto de Histología y Embriología-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.

Autophagy is the unique, regulated mechanism for the degradation of organelles. This intracellular process acts as a prosurvival pathway during cell starvation or stress and is also involved in cellular response against specific bacterial infections. Vibrio cholerae is a noninvasive intestinal pathogen that has been studied extensively as the causative agent of the human disease cholera. V. cholerae illness is produced primarily through the expression of a potent toxin (cholera toxin) within the human intestine. Besides cholera toxin, this bacterium secretes a hemolytic exotoxin termed V. cholerae cytolysin (VCC) that causes extensive vacuolation in epithelial cells. In this work, we explored the relationship between the vacuolation caused by VCC and the autophagic pathway. Treatment of cells with VCC increased the punctate distribution of LC3, a feature indicative of autophagosome formation. Moreover, VCC-induced vacuoles colocalized with LC3 in several cell lines, including human intestinal Caco-2 cells, indicating the interaction of the large vacuoles with autophagic vesicles. Electron microscopy analysis confirmed that the vacuoles caused by VCC presented hallmarks of autophagosomes. Additionally, biochemical evidence demonstrated the degradative nature of the VCC-generated vacuoles. Interestingly, autophagy inhibition resulted in decreased survival of Caco-2 cells upon VCC intoxication. Also, VCC failed to induce vacuolization in Atg5-/- cells, and the survival response of these cells against the toxin was dramatically impaired. These results demonstrate that autophagy acts as a cellular defense pathway against secreted bacterial toxins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.0601437104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794277PMC
February 2007

New carbenicillin-hydrolyzing beta-lactamase (CARB-7) from Vibrio cholerae non-O1, non-O139 strains encoded by the VCR region of the V. cholerae genome.

Antimicrob Agents Chemother 2002 Jul;46(7):2162-8

Servicio Antimicrobianos, Departamento de Bacteriología, Instituto Nacional de Enfermedades Infecciosas-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina.

In a previous study, an analysis of 77 ampicillin-nonsusceptible (resistant plus intermediate categories) strains of Vibrio cholerae non-O1, non-O139, isolated from aquatic environment and diarrheal stool, showed that all of them produced a beta-lactamase with a pI of 5.4. Hybridization or amplification by PCR with a probe for bla(TEM) or primers for bla(CARB) gene families was negative. In this work, an environmental ampicillin-resistant strain from this sample, ME11762, isolated from a waterway in the west region of Argentina, was studied. The nucleotide sequence of the structural gene of the beta-lactamase was determined by bidirectional sequencing of a Sau3AI fragment belonging to this isolate. The gene encodes a new 288-amino-acid protein, designated CARB-7, that shares 88.5% homology with the CARB-6 enzyme; an overall 83.2% homology with PSE-4, PSE-1, CARB-3, and the Proteus mirabilis N29 enzymes; and 79% homology with CARB-4 enzyme. The gene for this beta-lactamase could not be transferred to Escherichia coli by conjugation. The nucleotide sequence of the flanking regions of the bla(CARB-7) gene showed the occurrence of three 123-bp V. cholerae repeated sequences, all of which were found outside the predicted open reading frame. The upstream fragment of the bla(CARB-7) gene shared 93% identity with a locus situated inside V. cholerae's chromosome 2. These results strongly suggest the chromosomal location of the bla(CARB-7) gene, making this the first communication of a beta-lactamase gene located on the VCR island of the V. cholerae genome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC127289PMC
http://dx.doi.org/10.1128/aac.46.7.2162-2168.2002DOI Listing
July 2002