(FBIOyF) Departamento de Microbiología - Artículos

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Parasitosis intestinales en una población pediátrica de la ciudad de Rosario, Santa Fe, Argentina
(Federación Bioquímica de la Provincia de Buenos Aires, 2011-04) Indelman, Paula; Echenique, Claudia G.; Bertorini, Griselda; Racca, Liliana; Gomez, Carlos; Luque, Alicia Graciela; Magaró, Hortensia María
Las parasitosis intestinales afectan principalmente a los niños. El objetivo de este trabajo es conocer la situación actual en una población pediátrica de diferentes zonas de la ciudad de Rosario, Santa Fe (Argentina) y comparar la prevalencia parasitaria con estudios similares realizados en los períodos 1983/1984, 1990/1991, 1992/1993 y 2007/2008. Se recolectaron muestras de materia fecal por deposición espontánea de 112 pacientes, 51 niñas y 61 niños, con edades comprendidas entre 4 meses y 16 años, provenientes de 10 Centros de Atención Primaria de la Salud (Secretaría de Salud Pública - Municipalidad de Rosario). Las muestras fueron sometidas a examen macroscópico y microscópico directo y a métodos de concentración. En el período 2007/2008 los parásitos más hallados fueron Blastocystis hominis, Giardia lamblia y Ascaris lumbricoides. La prevalencia parasitaria disminuyó del 50% al 41%. Blastocystis hominis aumentó a través del tiempo; Giardia lamblia mantuvo valores constantes en las cuatro etapas; Entamoeba coli disminuyó en los últimos 14 años y Ascaris lumbricoides aumentó significativamente en relación con el período 1983/1984. Disminuyeron los individuos poliparasitados y aumentaron los monoparasitados con respecto a años anteriores. La disminución de las enteroparasitosis podría deberse a políticas de saneamiento ambiental, campañas de prevención y desparasitación realizadas desde los distintos efectores de salud municipales.
Acceso Abierto
Diversidad de ß-lactamasas en aislamientos clínicos de enterobacterias
(Federación Bioquímica de la Provincia de Buenos Aires, 2012-07) Casabonne, Cecilia; Pérez, Jorgelina; Balagué, Claudia Elizabeth; Fernández, Luisa
La rápida emergencia de resistencia a antimicrobianos debida a la presencia de b-lactamasas de espectro extendido (BLEE) tiene un impacto significativo en la salud pública. Las BLEEs son enzimas producidas por bacilos gramnegativos y confieren resistencia a las penicilinas, a todas las cefalosporinas y al aztreonam, pero no a los carbapenemes ni a las cefamicinas y la mayoría son inhibidas por el ácido clavulánico. El objetivo de este trabajo fue evaluar la resistencia a antibióticos b-lactámicos en aislamientos de Klebsiella pneumoniae, Escherichia coli y Proteus mirabilis y caracterizar las b-lactamasas responsables de dicha resistencia. Se analizaron 2.030 aislamientos (362 Klebsiella pneumoniae, 1.250 Escherichia coli y 175 Proteus mirabilis) provenientes de diferentes materiales clínicos de pacientes que concurrieron al Hospital Provincial del Centenario de la ciudad de Rosario (Santa Fe) durante el período 2008-2009. Los ensayos de sensibilidad antibiótica se realizaron de acuerdo con las recomendaciones del Clinical and Laboratory Standard Institute. Se confirmó la presencia de los genes codificantes de BLEE blaTEM, blaSHV, blaCTX-M y blaPER mediante la reacción en cadena de la polimerasa (PCR) utilizando cebadores específicos. Los aislados fueron caracterizados fenotípicamente como productores de BLEE y demostraron poseer varios genes bla. Se detectaron tres diferentes b-lactamasas BLEE derivadas de SHV, TEM y CTX-M y se demostró que pueden coexistir dos o más de estos genes en una misma bacteria.
Acceso Abierto
Identificación de papilomavirus humanos en lesiones cutáneas benignas y malignas no melanoma por métodos moleculares.
(Medigraphic Literatura Biomédica, 2013) Piccirilli, Gustavo; Squeff, Mario; Quattrocchi, Cristian; Fernández Bussy, Ramón Alfredo; Chouhy, Diego; Gorosito, Mario; Sanchez, Adriana; Bergero, Adriana; Giri, Adriana Angélica; Fernández Bussy, Ramón Alfredo
Acceso Abierto
Staring at the cold sun: blue light regulation is distributed within the genus acinetobacter
(Public Library of Science (PLOS), 2013-01-24) Golic, Adrián Ezequiel; Vaneechoutte, Mario; Nemec, Alexandr; Viale, Alejandro M.; Actis, Luis A.; Mussi, María Alejandra
We previously showed that the opportunistic nosocomial pathogen Acinetobacter baumannii is able to sense and respond to light via BlsA, a BLUF (Blue-Light-sensing Using FAD)-domain photoreceptor protein. Here, we extend our previous studies showing that light regulation is not restricted to A. baumannii, but rather widespread within the genus Acinetobacter. First, we found that blue light modulates motility and biofilm formation in many species of the genus, including members of the Acinetobacter calcoaceticus-A. baumannii complex. In many of these species blue light acts as a key factor guiding the decision between motility or sessility at 24°C, whereas in A. baumannii, light inhibits both motility and biofilm formation. We also show that light regulation of motility occurred not only at 24°C but also at 37°C in non-A. baumannii species, contrasting the situation of A. baumannii which only shows photoregulation at 24°C. Second, we show that Acinetobacter baylyi (strain ADP1) BLUF-photoreceptors can functionally replace in vivo the A. baumannii 17978 BlsA protein and that the pathways leading to biofilm formation are inversely regulated at 24°C between these two microorganisms. Finally, we found the presence of predicted genes coding BLUF-containing proteins in all Acinetobacter sequenced genomes, even though the copy number is variable among them. Phylogenetic analysis suggests a common origin for all BLUF domains present in members of this genus, and could distinguish well-differentiated clusters that group together BLUF homologs from different species, a situation particularly clear for members of the ACB complex. Despite a role played by these BLUF domain-containing proteins in the photoregulation observed in the members of the genus Acinetobacter is a likely scenario given our findings in A. baumannii and A. baylyi, further research will contribute to confirm this possibility.
Acceso Abierto
Prevalence of human papillomavirus infection in Argentinean women attending two different hospitals prior to the implementation of the National vaccination program.
(Wiley, 2013-04) Chouhy, Diego; Mamprín D´Andrea, Rubén; Iglesias, Mercedes; Messina, Analía; Ivancovich, Juan José; Cerda, Belén; Galimberti, Diana; Bottai, Hebe; Giri, Adriana Angélica
Acceso Abierto
Phage biocontrol of enteropathogenic and shiga toxin-producing Escherichia coli in meat products
(Frontiers Media, 2013-06-06) Tomat, David Damián; Migliore, Leonel; Aquili, Virginia; Quiberoni, Andrea; Balagué, Claudia Elizabeth
Ten bacteriophages were isolated from faeces and their lytic effects assayed on 103 pathogenic and non-pathogenic Enterobacteriaceae. Two phages (DT1 and DT6) were selected based on their host ranges, and their lytic effects on pathogenic E. coli strains inoculated on pieces of beef were determined. We evaluated the reductions of viable cells of Escherichia coli O157:H7 and non-O157 Shiga toxigenic E. coli strains on meat after exposure to DT6 at 5 and 24◦C for 3, 6, and 24 h and the effect of both phages against an enteropathogenic E. coli strain. Significant viable cell reductions, compared to controls without phages, at both temperatures were observed, with the greatest decrease taking place within the first hours of the assays. Reductions were also influenced by phage concentration, being the highest concentrations, 1.7 × 10 10 plaque forming units per milliliter (PFU/mL) for DT1 and 1.4 × 10 10 PFU/mL for DT6, the most effective. When enteropathogenic E. coli and Shiga toxigenic E. coli (O157:H7) strains were tested, we obtained viable cell reductions of 0.67 log (p = 0.01) and 0.77 log (p = 0.01) after 3 h incubation and 0.80 log (p = 0.01) and 1.15 log (p = 0.001) after 6 h. In contrast, all nonpathogenic E. coli strains as well as other enterobacteria tested were resistant. In addition, phage cocktail was evaluated on two strains and further reductions were observed. However, E. coli bacteriophage insensitive mutants (BIMs) emerged in meat assays. BIMs isolated from meat along with those isolated by using the secondary culture method were tested to evaluate resistance phenotype stability and reversion. They presented low emergence frequencies (6.5 × 10−7 –1.8 × 10−6 ) and variable stability and reversion. Results indicate that isolated phages were stable on storage, negative for all the virulence factors assayed, presented lytic activity for different E. coli virotypes and could be useful in reducing Shiga toxigenic E. coli and enteropathogenic E. coli viable cells in meat products.
Acceso Abierto
Unsaturated long chain free fatty acids are input signals of the Salmonella enterica PhoP/PhoQ regulatory system
(American Society for Biochemistry and Molecular Biology, 2013-08-02) Viarengo, Gastón; Sciara, Mariela Inés; Salazar, Mario Oscar; Kieffer, Pablo M.; Furlán, Ricardo Luis Eugenio; García Véscovi, Eleonora
The Salmonella enterica serovar Typhimurium PhoP/PhoQ system has largely been studied as a paradigmatic two-component regulatory system not only to dissect structural and functional aspects of signal transduction in bacteria but also to gain knowledge about the versatile devices that have evolved allowing a pathogenic bacterium to adjust to or counteract environmental stressful conditions along its life cycle. Mg2+ limitation, acidic pH, and the presence of cationic antimicrobial peptides have been identified as cues that the sensor protein PhoQ can monitor to reprogram Salmonella gene expression to cope with extra- or intracellular challenging conditions. In this work, we show for the first time that long chain unsaturated free fatty acids (LCUFAs) present in Salmonella growth medium are signals specifically detected by PhoQ. We demonstrate that LCUFAs inhibit PhoQ autokinase activity, turning off the expression of the PhoP-dependent regulon. We also show that LCUFAs exert their action independently of their cellular uptake and metabolic utilization by means of the β-oxidative pathway. Our findings put forth the complexity of input signals that can converge to finely tune the activity of the PhoP/PhoQ system. In addition, they provide a new potential biochemical platform for the development of antibacterial strategies to fight against Salmonella infections.
Acceso Abierto
Expression of the agmatine deiminase pathway in Enterococcus faecalis is activated by the AguR regulator and repressed by CcpA and PTS(Man) systems
(Public Library of Science, 2013-10-14) Suárez, Cristian Alejandro; Espariz, Martín; Blancato, Víctor Sebastián; Magni, Christian
Although the agmatine deiminase system (AgDI) has been investigated in Enterococcus faecalis, little information is available with respect to its gene regulation. In this study we demonstrate that the presence of exogenous agmatine induces the expression of agu genes in this bacterium. In contrast to the homologous and extensively characterized AgDI system of S. mutants, the aguBDAC operon in E. faecalis is not induced in response to low pH. In spite of this, agmatine catabolism in this bacterium contributes by neutralizing the external medium while enhancing bacterial growth. Our results indicate that carbon catabolic repression (CCR) operates on the AgDI system via a mechanism that involves interaction of CcpA and PSer-HPr with a cre site found in an unusual position considering the aguB promoter (55 nt upstream the +1 position). In addition, we found that components of the mannose phosphotransferase (PTSMan) system also contributed to CCR in E. faecalis since a complete relief of the PTS-sugars repressive effect was observed only in a PTSMan and CcpA double defective strain. Our gene context analysis revealed that aguR is present in oral and gastrointestinal microorganisms. Thus, regulation of the aguBDAC operon in E. faecalis seems to have evolved to obtain energy and resist low pH conditions in order to persist and colonize gastrointestinal niches.
Acceso Abierto
Analysis of the genetic diversity and phylogenetic relationships of putative human papillomavirus types
(2013-11) Chouhy, Diego; Bolatti, Elisa María; Perez, Germán Roberto; Giri, Adriana Angélica
Acceso Abierto
Host-specific enzyme-substrate interactions in SPM-1 metallo-β-lactamase are modulated by second sphere residues
(Public Library of Science (PLOS), 2014-01-02) González, Lisandro Javier; Moreno, Diego M.; Bonomo, Robert A.; Vila, Alejandro J.
Pseudomonas aeruginosa is one of the most virulent and resistant non-fermenting Gram-negative pathogens in the clinic. Unfortunately, P. aeruginosa has acquired genes encoding metallo-β-lactamases (MβLs), enzymes able to hydrolyze most β-lactam antibiotics. SPM-1 is an MβL produced only by P. aeruginosa, while other MβLs are found in different bacteria. Despite similar active sites, the resistance profile of MβLs towards β-lactams changes from one enzyme to the other. SPM-1 is unique among pathogen-associated MβLs in that it contains “atypical” second sphere residues (S84, G121). Codon randomization on these positions and further selection of resistance-conferring mutants was performed. MICs, periplasmic enzymatic activity, Zn(II) requirements, and protein stability was assessed. Our results indicated that identity of second sphere residues modulates the substrate preferences and the resistance profile of SPM-1 expressed in P. aeruginosa. The second sphere residues found in wild type SPM-1 give rise to a substrate selectivity that is observed only in the periplasmic environment. These residues also allow SPM-1 to confer resistance in P. aeruginosa under Zn(II)-limiting conditions, such as those expected under infection. By optimizing the catalytic efficiency towards β-lactam antibiotics, the enzyme stability and the Zn(II) binding features, molecular evolution meets the specific needs of a pathogenic bacterial host by means of substitutions outside the active site.
Acceso Abierto
Human papillomavirus (HPV)-18 E6 oncoprotein interferes with the epithelial cell polarity Par3 protein
(Federation of European Biochemical Societies, 2014-01-14) Facciuto, Florencia Natalia; Bugnon Valdano, Marina Paula; Marziali, Federico Emanuel; Massimi, Paola; Banks, Lawrence; Cavatorta, Ana Laura; Gardiol, Daniela
Acceso Abierto
Cerulenin inhibits unsaturated fatty acids synthesis in Bacillus subtilis by modifying the input signal of DesK thermosensor
(Wiley, 2014-04-09) Porrini, Lucía; Cybulski, Larisa Estefanía; Altabe, Silvia Graciela; Mansilla, María Cecilia; De Mendoza, Diego
Bacillus subtilis responds to a sudden decrease in temperature by transiently inducing the expression of the des gene encoding for a lipid desaturase, Δ5-Des, which introduces a double bond into the acyl chain of preexisting membrane phospholipids. This Δ5-Des-mediated membrane remodeling is controlled by the cold-sensor DesK. After cooling, DesK activates the response regulator DesR, which induces transcription of des. We show that inhibition of fatty acid synthesis by the addition of cerulenin, a potent and specific inhibitor of the type II fatty acid synthase, results in increased levels of short-chain fatty acids (FA) in membrane phospholipids that lead to inhibition of the transmembrane-input thermal control of DesK. Furthermore, reduction of phospholipid synthesis by conditional inactivation of the PlsC acyltransferase causes significantly elevated incorporation of long-chain FA and constitutive upregulation of the des gene. Thus, we provide in vivo evidence that the thickness of the hydrophobic core of the lipid bilayer serves as one of the stimulus sensed by the membrane spanning region of DesK.
Acceso Abierto
Genomic comparative analysis of the environmental Enterococcus mundtii against enterococcal representative species
(BMC, 2014-06-18) Repizo, Guillermo Daniel; Espariz, Martín; Blancato, Víctor Sebastián; Suárez, Cristian Alejandro; Esteban, Luis; Magni, Christian
Background Enterococcus mundtii is a yellow-pigmented microorganism rarely found in human infections. The draft genome sequence of E. mundtii was recently announced. Its genome encodes at least 2,589 genes and 57 RNAs, and 4 putative genomic islands have been detected. The objective of this study was to compare the genetic content of E. mundtii with respect to other enterococcal species and, more specifically, to identify genes coding for putative virulence traits present in enterococcal opportunistic pathogens. Results An in-depth mining of the annotated genome was performed in order to uncover the unique properties of this microorganism, which allowed us to detect a gene encoding the antimicrobial peptide mundticin among other relevant features. Moreover, in this study a comparative genomic analysis against commensal and pathogenic enterococcal species, for which genomic sequences have been released, was conducted for the first time. Furthermore, our study reveals significant similarities in gene content between this environmental isolate and the selected enterococci strains (sharing an “enterococcal gene core” of 805 CDS), which contributes to understand the persistence of this genus in different niches and also improves our knowledge about the genetics of this diverse group of microorganisms that includes environmental, commensal and opportunistic pathogens. Conclusion Although E. mundtii CRL1656 is phylogenetically closer to E. faecium, frequently responsible of nosocomial infections, this strain does not encode the most relevant relevant virulence factors found in the enterococcal clinical isolates and bioinformatic predictions indicate that it possesses the lowest number of putative pathogenic genes among the most representative enterococcal species. Accordingly, infection assays using the Galleria mellonella model confirmed its low virulence.
Acceso Abierto
Systematic production of inactivating and non-inactivating suppressor mutations at the relA locus that compensate the detrimental effects of complete spoT loss and affect glycogen content in Escherichia coli
(Public Library of Science, 2014-09-04) Montero, Manuel; Rahimpour, Mehdi; Viale, Alejandro M.; Almagro, Goizeder; Eydallin, Gustavo; Sevilla, Ángel; Cánovas, Manuel; Bernal, Cristina; Muñoz, Francisco José; Baroja Fernández, Edurne; Bahaji, Abdellatif; Mori, Hirotada; Codoñer, Francisco M.; Pozueta Romero, Javier
In Escherichia coli, ppGpp is a major determinant of growth and glycogen accumulation. Levels of this signaling nucleotide are controlled by the balanced activities of the ppGpp RelA synthetase and the dual-function hydrolase/synthetase SpoT. Here we report the construction of spoT null (DspoT) mutants obtained by transducing a DspoT allele from DrelADspoT double mutants into relA+ cells. Iodine staining of randomly selected transductants cultured on a rich complex médium revealed differences in glycogen content among them. Sequence and biochemical analyses of 8 DspoT clones displaying glycogen-deficient phenotypes revealed different inactivating mutations in relA and no detectable ppGpp when cells were cultured on a rich complex medium. Remarkably, although the co-existence of DspoT with relA proficient alleles has generally been considered synthetically lethal, we found that 11 DspoT clones displaying high glycogen phenotypes possessed relA mutant alleles with non-inactivating mutations that encoded stable RelA proteins and ppGpp contents reaching 45–85% of those of wild type cells. None of the DspoT clones, however, could grow on M9-glucose minimal medium. Both Sanger sequencing of specific genes and high-throughput genome sequencing of the DspoT clones revealed that suppressor mutations were restricted to the relA locus. The overall results (a) defined in around 4 nmoles ppGpp/g dry weight the threshold cellular levels that suffice to trigger net glycogen accumulation, (b) showed that mutations in relA, but not necessarily inactivating mutations, can be selected to compensate total SpoT function(s) loss, and (c) provided useful tools for studies of the in vivo regulation of E. coli RelA ppGpp synthetase.
Acceso Abierto
Construction of three new Gateway® expression plasmids for Trypanosoma cruzi
(Instituto Oswaldo Cruz, 2014-12) Alonso, Victoria Lucía; Ritagliati, Carla; Cribb, Pamela; Serra, Esteban Carlos
We present here three expression plasmids for Trypanosoma cruzi adapted to the Gateway® recombination cloning system. Two of these plasmids were designed to express trypanosomal proteins fused to a double tag for tandem affinity purification (TAPtag). The TAPtag and Gateway® cassette were introduced into an episomal (pTEX) and an integrative (pTREX) plasmid. Both plasmids were assayed by introducing green fluorescent protein (GFP) by recombination and the integrity of the double-tagged protein was determined by western blotting and immunofluorescence microscopy. The third Gateway adapted vector assayed was the inducible pTcINDEX. When tested with GFP, pTcINDEX-GW showed a good response to tetracycline, being less leaky than its precursor (pTcINDEX).
Acceso Abierto
Genome announcement : complete genome sequence of a novel Mupapillomavirus, HPV204
(Association of Slovenian Dermatovenerologists, 2015) Chouhy, Diego; Bolatti, Elisa María; Giri, Adriana Angélica; Poljak, Mario; Kocjan, Boštjan J.; Šterbenc, Anja; Hošnjak, Lea
Acceso Abierto
Comparative genomic and phylogenetic analyses of gammaproteobacterial glg genes traced the origin of the Escherichia coli glycogen glgBXCAP pperon to the last common ancestor of the sister orders enterobacteriales and pasteurellales
(Public Library of Science, 2015-01-21) Almagro, Goizeder; Viale, Alejandro M.; Montero, Manuel; Rahimpour, Mehdi; Muñoz, Francisco José; Baroja Fernández, Edurne; Bahaji, Abdellatif; Zúñiga, Manuel; González Candelas, Fernando; Pozueta Romero, Javier
Production of branched α-glucan, glycogen-like polymers is widely spread in the Bacteria domain. The glycogen pathway of synthesis and degradation has been fairly well characterized in the model enterobacterial species Escherichia coli (order Enterobacteriales, class Gammaproteobacteria), in which the cognate genes (branching enzyme glgB, debranching enzyme glgX, ADP-glucose pyrophosphorylase glgC, glycogen synthase glgA, and glycogen phosphorylase glgP) are clustered in a glgBXCAP operon arrangement. However, the evolutionary origin of this particular arrangement and of its constituent genes is unknown. Here, by using 265 complete gammaproteobacterial genomes we have carried out a comparative analysis of the presence, copy number and arrangement of glg genes in all lineages of the Gammaproteobacteria. These analyses revealed large variations in glg gene presence, copy number and arrangements among different gammaproteobacterial lineages. However, the glgBXCAP arrangement was remarkably conserved in all glg-possessing species of the orders Enterobacteriales and Pasteurellales (the E/P group). Subsequent phylogenetic analyses of glg genes present in the Gammaproteobacteria and in other main bacterial groups indicated that glg genes have undergone a complex evolutionary history in which horizontal gene transfer may have played an important role. These analyses also revealed that the E/P glgBXCAP genes (a) share a common evolutionary origin, (b) were vertically transmitted within the E/P group, and (c) are closely related to glg genes of some phylogenetically distant betaproteobacterial species. The overall data allowed tracing the origin of the E. coli glgBXCAP operon to the last common ancestor of the E/P group, and also to uncover a likely glgBXCAP transfer event from the E/P group to particular lineages of the Betaproteobacteria.
Acceso Abierto
Transcriptional and translational mechanisms contribute to regulate the expression of Disc Large 1 protein during different biological processes
(De Gruyter, 2015-03-14) Marziali, Federico Emanuel; Cavatorta, Ana Laura; Bugnon Valdano, Marina Paula; Facciuto, Florencia Natalia; Gardiol, Daniela; ; ; ; ; ;
Acceso Abierto
The dual nature of trehalose in citrus canker disease: a virulence factor for Xanthomonas citri subsp. citri and a trigger for plant defence responses
(Oxford University, 2015-03-15) Piazza, Ainelén; Zimaro, Tamara; Garavaglia, Betiana Soledad; Ficarra, Florencia Andrea; Thomas, Ludivine; Marondedze, Claudius; Feil, Regina; Lunn, John E.; Gehring, Chris; Ottado, Jorgelina; Gottig, Natalia
Xanthomonas citri subsp. citri (Xcc) is a bacterial pathogen that causes citrus canker in susceptible Citrus spp. The Xcc genome contains genes encoding enzymes from three separate pathways of trehalose biosynthesis. Expression of genes encoding trehalose-6-phosphate synthase (otsA) and trehalose phosphatase (otsB) was highly induced during canker development, suggesting that the two-step pathway of trehalose biosynthesis via trehalose-6-phosphate has a function in pathogenesis. This pathway was eliminated from the bacterium by deletion of the otsA gene. The resulting XccΔotsA mutant produced less trehalose than the wild-type strain, was less resistant to salt and oxidative stresses, and was less able to colonize plant tissues. Gene expression and proteomic analyses of infected leaves showed that infection with XccΔotsA triggered only weak defence responses in the plant compared with infection with Xcc, and had less impact on the host plant’s metabolism than the wild-type strain. These results suggested that trehalose of bacterial origin, synthesized via the otsA–otsB pathway, in Xcc, plays a role in modifying the host plant’s metabolism to its own advantage but is also perceived by the plant as a sign of pathogen attack. Thus, trehalose biosynthesis has both positive and negative consequences for Xcc. On the one hand, it enables this bacterial pathogen to survive in the inhospitable environment of the leaf surface before infection and exploit the host plant’s resources after infection, but on the other hand, it is a tell-tale sign of the pathogen’s presence that triggers the plant to defend itself against infection.
Acceso Abierto
Overexpression of cytoplasmic TcSIR2RP1 and mitochondrial TcSIR2RP3 impacts on Trypanosoma cruzi growth and cell invasion
(Public Library of Science (PLOS), 2015-04-15) Ritagliati, Carla; Alonso, Victoria Lucía; Manarin, Romina; Cribb, Pamela; Serra, Esteban Carlos
Abstract Background Trypanosoma cruzi is a protozoan pathogen responsible for Chagas disease. Current therapies are inadequate because of their severe host toxicity and numerous side effects. The identification of new biotargets is essential for the development of more efficient therapeutic alternatives. Inhibition of sirtuins from Trypanosoma brucei and Leishmania ssp. Showed promising results, indicating that these enzymes may be considered as targets for drug discovery in parasite infection. Here, we report the first characterization of the two sirtuins present in T. cruzi. Methodology Dm28c epimastigotes that inducibly overexpress TcSIR2RP1 and TcSIR2RP3 were constructed and used to determine their localizations and functions. These transfected lines were tested regarding their acetylation levels, proliferation and metacyclogenesis rate, viability when treated with sirtuin inhibitors and in vitro infectivity. Conclusion TcSIR2RP1 and TcSIR2RP3 are cytosolic and mitochondrial proteins respectively. Our data suggest that sirtuin activity is important for the proliferation of T. cruzi replicative forms, for the host cell-parasite interplay, and for differentiation among life-cycle stages; but each one performs different roles in most of these processes. Our results increase the knowledge on the localization and function of these enzymes, and the overexpressing T. cruzi strains we obtained can be useful tools for experimental screening of trypanosomatid sirtuin inhibitors.

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