Hector Alex Saka | Universidad Nacional de Córdoba (original) (raw)

Papers by Hector Alex Saka

Frontiers in cellular and infection microbiology, Feb 6, 2024

Frontiers in Cellular and Infection Microbiology, Aug 16, 2023

Journal of Clinical Microbiology, 2006

Since 1999, a new, epidemic, methicillin-resistant Staphylococcus aureus (MRSA) strain, named the... more Since 1999, a new, epidemic, methicillin-resistant Staphylococcus aureus (MRSA) strain, named the "Cordobes clone," has emerged in Argentina and coexists with the pandemic Brazilian clone. The purpose of this study was to determine the stability over time of the new clone and to investigate its evolutionary relationship with epidemic international MRSA lineages and with other MRSA and methicillin-susceptible S. aureus (MSSA) major clones distributed in this region. One hundred three MRSA isolates recovered in 2001 from Cordoba, Argentina, hospitals and 31 MSSA strains collected from 1999 to 2002 were analyzed by their antibiotic resistance patterns, phage typing, and pulsed-field gel electrophoresis. Additionally, representative members of most MRSA defined genotypes (A, B, C, E, K, and I) were characterized by multilocus sequence typing (MLST) and spaA and SCCmec typing. The most prevalent MSSA pulsotypes were also analyzed by MLST. Our results support the displacement of the Brazilian clone (sequence type [ST] 239, spaA type WGKAOMQ, SCCmec type IIIA) by the Cordobes clone (ST5, spaA type TIMEMDMGMGMK, SCCmec type I) in the hospital environment. MRSA and MSSA isolates shared only ST5. The data support the origin of the Cordobes clone as a member of a lineage that includes the pediatric and New York/Japan international clones and that is genetically related to the British EMRSA-3 strain. Interestingly, the pediatric clone, isolated from most community-acquired infections in Cordoba, was characterized by ST100, a single-locus variant of ST5 and a new variant of SCCmec type related to SCCmec type IVc.

Revista Chilena De Infectologia, Aug 1, 2020

Introducción: Las enterobacterias son una causa principal de infecciones del torrente sanguíneo y... more Introducción: Las enterobacterias son una causa principal de infecciones del torrente sanguíneo y su resistencia antimicrobiana se encuentra en aumento. Esto lleva a un incremento de la morbilidadmortalidad y de los costos en la salud pública. Las enterobacterias resistentes a carbapenems representan un grave desafío a nivel global ya que existen escasas opciones terapéuticas disponibles. Objetivo: Caracterización clínico/microbiológica de las bacteriemias resistentes a carbapenémicos observadas en un período de 4 años. Material y Método: Estudio retrospectivo, observacional y descriptivo, sobre las bacteriemias por enterobacterias resistentes y sensibles a carbapenems. Resultados: Se analizó un total de 84 pacientes con bacteriemia por enterobacterias resistentes y sensibles a carbapenems. Entre las resistentes, observamos una mayor proporción de: tratamiento antimicrobiano previo, hospitalización en unidad de terapia intensiva (UTI), inicio de la bacteriemia en UTI y antecedentes de β-lactamasas de espectro extendido. Además, se detectó un amplio predominio de Klebsiella pneumoniae productor de KPC y una mortalidad atribuible de 52,4%. Discusión: El estudio posibilitó profundizar el conocimiento de una enfermedad emergente de elevada mortalidad, en vistas al diseño y aplicación de estrategias de control de infecciones y de esquemas de tratamiento efectivos adaptados a la epidemiologia local.

Frontiers in Cellular and Infection Microbiology, 2018

c-Jun is a member of the early mammalian transcriptional regulators belonging to the AP-1 family,... more c-Jun is a member of the early mammalian transcriptional regulators belonging to the AP-1 family, which participates in a wide range of cellular processes such as proliferation, apoptosis, tumorigenesis, and differentiation. Despite its established role in cell survival upon stress, its participation in the stress response induced by bacterial infections has been poorly investigated. To study the potential role of c-Jun in this context we choose the widely studied α-toxin produced by Staphylococcus aureus, a pore-forming toxin that is a critical virulence factor in the pathogenesis of these bacteria. We analyzed the effect of α-toxin treatment in the activation, expression, and protein levels of c-Jun in A549 lung epithelial cells. Furthermore, we explored the role of c-Jun in the cellular fate after exposure to α-toxin. Our results show that staphylococcal α-toxin per se is able to activate c-Jun by inducing phosphorylation of its Serine 73 residue. Silencing of the JNK (c-Jun N-terminal Kinase) signaling pathway abrogated most of this activation. On the contrary, silencing of the ERK (Extracellular Signal-Regulated Kinase) pathway exacerbated this response. Intriguingly, while the exposure to α-toxin induced a marked increase in the levels of c-Jun transcripts, c-Jun protein levels noticeably decreased in the same time-frame as a consequence of active proteolytic degradation through the proteasome-dependent pathway. In addition, we established that c-Jun promoted cell survival when cells were challenged with α-toxin. Similarly, c-Jun phosphorylation was also induced in cells upon intoxication with the cytolysin produced by Vibrio cholerae in a JNK-dependent manner, suggesting that c-Jun-JNK axis would be a conserved responsive cellular pathway to pore-forming toxins. This study contributes to understanding the role of the multifaceted c-Jun proto-oncoprotein in cell response to bacterial pore-forming toxins, positioning it as a relevant component of the complex early machinery mounted to deal with staphylococcal infections.

Reproduction (Cambridge, England), Oct 1, 2017

Chlamydia trachomatis is the most commonly reported agent of sexually transmitted bacterial infec... more Chlamydia trachomatis 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 Chlamydia trachomatis 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 Chlamydia trachomatis, which in turn may result in T helper 1-mediated protection or in T helper 2-m...

International Journal of Paleopathology, 2021

OBJECTIVE Detecting traces of ancient DNA of Vibrio cholerae to provide genetic information assoc... more 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.

Annual Review of Cell and Developmental Biology, Nov 10, 2012

Lipid droplets (LDs) are neutral lipid storage organelles ubiquitous to eukaryotic cells. It is i... more 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.

Antimicrobial Agents and Chemotherapy, Oct 1, 2004

The gene bla CARB-9 was located in the Vibrio cholerae super-integron, but in a different locatio... more The gene bla CARB-9 was located in the Vibrio cholerae super-integron, but in a different location relative to bla CARB-7. CARB-9 (pI 5.2) conferred ␤-lactam MICs four to eight times lower than those conferred by CARB-7, differing at Ambler's positions V97I, L124F, and T228K. Comparison of the genetic environments of all reported bla CARB genes indicated that the CARB enzymes constitute a family of cassette-encoded ␤-lactamases.

Antimicrobial Agents and Chemotherapy, Jul 1, 2002

In a previous study, an analysis of 77 ampicillin-nonsusceptible (resistant plus intermediate cat... more 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 ␤-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 ampicillinresistant 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 ␤-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 ␤-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 ␤-lactamase gene located on the VCR island of the V. cholerae genome.

Microbial Pathogenesis, Feb 1, 2008

Vibrio cholerae cytolysin is essential for high enterotoxicity and apoptosis induction produced b... more 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

PLOS Pathogens, Feb 20, 2014

Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted infections, emplo... more Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted infections, employs a type III secretion (T3S) system to deliver effector proteins into host epithelial cells to establish a replicative vacuole. Aside from the phosphoprotein TARP, a Chlamydia effector that promotes actin rearrangements , very few factors mediating bacterial entry and early inclusion establishment have been characterized. Like many T3S effectors, TARP requires a chaperone (Slc1) for efficient translocation into host cells. In this study, we defined proteins that associate with Slc1 in invasive C. trachomatis elementary bodies (EB) by immunoprecipitation coupled with mass spectrometry. We identified Ct875, a new Slc1 client protein and T3S effector, which we renamed TepP (Translocated early phosphoprotein). We provide evidence that T3S effectors form large molecular weight complexes with Scl1 in vitro and that Slc1 enhances their T3S-dependent secretion in a heterologous Yersinia T3S system. We demonstrate that TepP is translocated early during bacterial entry into epithelial cells and is phosphorylated at tyrosine residues by host kinases. However, TepP phosphorylation occurs later than TARP, which together with the finding that Slc1 preferentially engages TARP in EBs leads us to postulate that these effectors are translocated into the host cell at different stages during C. trachomatis invasion. TepP co-immunoprecipitated with the scaffolding proteins CrkI-II during infection and Crk was recruited to EBs at entry sites where it remained associated with nascent inclusions. Importantly, C. trachomatis mutants lacking TepP failed to recruit CrkI-II to inclusions, providing genetic confirmation of a direct role for this effector in the recruitment of a host factor. Finally, endocervical epithelial cells infected with a tepP mutant showed altered expression of a subset of genes associated with innate immune responses. We propose a model wherein TepP acts downstream of TARP to recruit scaffolding proteins at entry sites to initiate and amplify signaling cascades important for the regulation of innate immune responses to Chlamydia.

Proceedings of the National Academy of Sciences of the United States of America, Feb 6, 2007

Biosensors and Bioelectronics: X

Frontiers in Cellular and Infection Microbiology

IntroductionInfection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia t... more IntroductionInfection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia trachomatis (CT) infection and vice versa. Coinfection of HPV and CT in women is a very common and usually asymptomatic finding that has been linked to increased risk of cervical cancer. It has been demonstrated that CT facilitates the entry of multiple high risk HPV genotypes, leading to damage of the mucosal barrier and interfering with immune responses and viral clearance, which ultimately favours viral persistence and malignant transformation. Although the facilitating effects elicited by CT infection on viral persistence have been reported, little is known about the consequences of HPV infection on CT development.MethodsHerein, we took advantage of a genetically modified human cervical cell line co-expressing HPV-16 major oncogenic proteins E6 and E7, as an experimental model allowing to investigate the possible effects that HPV infection would have on CT development.Results and disc...

Frontiers in Public Health, 2023

Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of se... more Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of sexually transmitted infections worldwide. Chlamydia trachomatis genovars L1–L3 are responsible for lymphogranuloma venereum (LGV), an invasive sexually transmitted disease endemic in tropical and subtropical regions of Africa, South America, the Caribbean, India and South East Asia. The typical signs and symptoms of C. trachomatis LGV urogenital infections in men include herpetiform ulcers, inguinal buboes, and/or lymphadenopathies. Since 2003, endemic cases of proctitis and proctocolitis caused by C. trachomatis LGV emerged in Europe, mainly in HIV-positive men who have sex with men (MSM). Scarce data have been reported about unusual clinical presentations of C. trachomatis LGV urogenital infections. Herein, we report a case of a 36-year-old heterosexual, HIV-negative male declaring he did not have sex with men or trans women, who presented to the Urology and Andrology outpatient clinic ...

This article cites 42 articles, 27 of which can be accessed free

(A) Wildtype MEFs were treated overnight with OA and IFNγ and immunos... more (A) Wildtype MEFs were treated overnight with OA and IFNγ and immunostained for endogenous Irgm3 and for LDs using BODIPY. (B) Wildtype MEFs were transfected with the three mouse paralogs Irgm1-3 tagged with V5, infected with C. trachomatis and treated with OA and IFNγ at 3 hpi. Cells were fixed at 20 hpi and stained with anti-V5, BODIPY and Hoechst. White arrows point at inclusions. (C) The localization of the GKS proteins Irga6 and Irgb6 were visualized in wildtype and Irgm1/m3−/− MEFs treated overnight with OA and IFNγ. (D) Cells were treated overnight with OA and IFNγ and stained with anti-Irgb10, BODIPY and Hoechst. Representative images are shown. Overlap in fluorescence signals derived from anti-Irgb10 and BODIPY stains is shown for these representative images. Data were analyzed as described in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003414#s4" target="_blank">Materials and Methods</a> and representative data of three independent experiments are shown. Statistical significance of group values relative to wildtype and between marked groups is shown (***, p<0.005). (E) LDs and total cell lysate were obtained from wildtype, Irgm1/m3−/− and Atg5−/− MEFs treated overnight with OA +/− IFNγ and analyzed by immunoblotting.</p