Staphylococcus aureus resistente a oxacilina por mecanismos alternativos a la presencia del gen mecA
Staphylococcus aureus is part of skin and mucous membranes colonizing flora, both in humans and animals. However, this opportunistic microorganism is one of the most common and important pathogens isolated both from nosocomial and community environments, responsible for a variety of infections such...
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| Formato: | Tesis de maestría acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2016
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1631 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1631.dir/1631.PDF |
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| Sumario: | Staphylococcus aureus is part of skin and mucous membranes colonizing flora, both in humans and animals. However, this opportunistic microorganism is one of the most common and important pathogens isolated both from nosocomial and community environments, responsible for a variety of infections such as endocarditis, osteomyelitis, and sepsis.\nFour clinical isolates of S. aureus recovered from a patient who suffered four consecutive episodes of bacteremia were characterized in this work. The first three isolates were susceptible to cefoxitin (FOX) and oxacillin (OXA), while the latter was resistant to OXA.\nThe isogenicity of the four isolates was determined by PFGE. Genotyping indicated that these isolates belong to ST8, spa type 024. This lineage is not prevalent in Argentina. The first isolate (SAMS1) and the last one (SA2) were further studied, considering the rare phenotype observed in SA2 (FOX sensitivity and OXA resistance).\nMolecular detection of the mecA gene, the most common mechanism associated with OXA resistance, was negative. The presence of mecC gene and recombinase genes described in different SCCmec were also discarded. Consequently, alternative mechanisms that could explain this phenotype were evaluated.\nNo mutations in pbp4 gene were detected among isolates.\nThe SA2 isolate showed higher ?-lactamase activity than the SAMS1 isolate. However, no mutations in the bla operon, that could justify this overproduction, were found.\nComparison of SA2 and SAMS1 pbp2 gene sequences revealed a mutation at nucleotide 1350, resulting in an Ala450Asp substitution. This change was not detected in the SAMS3 strain (isolated in the third episode of bacteremia), suggesting that this mutation could be linked with the emergence of oxacillin resistance in SA2\nA tridimensional model showed the replacement of a hydrophobic aminoacid such\nas alanine, by an acid one as aspartic, placed in a hydrophobic environment close to the\nactive site cavity of the transpeptidase domain of SA2 PBP2. This change would generate\ndistortions that could hinder the OXA molecule entrance.\nBoth ?-lactamase overproduction and PBP2 Ala450Asp substitution described in\nSA2 strain, would contribute to the resistance phenotype described herein. The possible\ncoexistence of other molecular mechanisms that could contribute to the oxacillin\nresistance could not be discarded.\nDetection of oxacillin resistant, mec negative isolates, represents a major challenge\nfor clinical laboratories, since they are not detected using FOX disc diffusion method.\nThis work demonstrates the emergence of OXA resistant S. aureus isolates in Argentina\nthat are not detected with current CLSI recommendations. |
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