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Genetic variation in spatio-temporal confined USA300 community-associated MRSA isolates: a shift from clonal dispersion to genetic evolution?

ABSTRACT: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA has been limited to isolates belonging to USA300. The aim of this study was to compare the genetic repertoire of different CA-MRSA clones with that of HA-MRSA from the USA and Europe through comparative genomic hybridization (CGH) to identify genetic clues that may explain the successful and rapid emergence of CA-MRSA.Hierarchical clustering based on CGH of 48 MRSA isolates from the community and nosocomial infections from Europe and the USA revealed dispersed clustering of the 19 CA-MRSA isolates. This means that these 19 CA-MRSA isolates do not share a unique genetic make-up. Only the PVL genes were commonly present in all CA-MRSA isolates. However, 10 genes were variably present among 14 USA300 isolates. Most of these genes were present on mobile elements.The genetic variation present among the 14 USA300 isolates is remarkable considering the fact that the isolates were recovered within one month and originated from a confined geographic area, suggesting continuous evolution of this clone.

SUBMITTER: Carpaij N

PROVIDER: S-EPMC3033884 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Genetic variation in spatio-temporal confined USA300 community-associated MRSA isolates: a shift from clonal dispersion to genetic evolution?

Carpaij Neeltje N Willems Rob J L RJ Rice Thomas W TW Weinstein Robert A RA Hinds Jason J Witney Adam A AA Lindsay Jodi A JA Bonten Marc J M MJ Fluit Ad C AC

PloS one 20110204 2

<h4>Introduction</h4>Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA ...[more]

PMID: 21326601

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Project description:An isolate of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 with reduced susceptibility to vancomycin (SG-R) (i.e, vancomycin-intermediate S. aureus, VISA) and its susceptible "parental" strain (SG-S) were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev). The availability of these 3 isogenic strains allowed us to explore genetic correlates of antibiotic resistance as it emerged in vivo. Compared to the susceptible isolate, both the VISA and revertant strains carried the same point mutations in yycH, vraG, yvqF and lspA genes and a substantial deletion within an intergenic region. The revertant strain carried a single additional frameshift mutation in vraS which is part of two component regulatory system VraSR. VISA isolate SG-R showed complex alterations in phenotype: decreased susceptibility to other antibiotics, slow autolysis, abnormal cell division and increased thickness of cell wall. There was also altered expression of 239 genes including down-regulation of major virulence determinants. All phenotypic properties and gene expression profile returned to parental levels in the revertant strain. Introduction of wild type yvqF on a multicopy plasmid into the VISA strain caused loss of resistance along with loss of all the associated phenotypic changes. Introduction of the wild type vraSR into the revertant strain caused recovery of VISA type resistance. The yvqF/vraSR operon seems to function as an on/off switch: mutation in yvqF in strain SG-R turns on the vraSR system, which leads to increase in vancomycin resistance and down-regulation of virulence determinants. Mutation in vraS in the revertant strain turns off this regulatory system accompanied by loss of resistance and normal expression of virulence genes. Down-regulation of virulence genes may provide VISA strains with a "stealth" strategy to evade detection by the host immune system.

Project description:IntroductionLymphogranuloma venereum (LGV) is already endemic in vulnerable populations in several European countries; however, molecular epidemiology data with improved accuracy are necessary to better understand LGV epidemic in these countries. Current strategies to study the molecular epidemiology of LGV cases involve schemes based on a few genetic fragments of Chlamydia trachomatis, which have demonstrated limited discriminatory power for LGV. Therefore, this study aimed to propose a new combination of molecular markers based on the most variable genes of L-genotype genomes to improve the characterization of the current LGV epidemic in Madrid, Spain.MethodsFour genes were selected according to their diversity index (CTLon_0054, CTLon_0087, CTLon_0243 and CTLon_0301) for use in combination with ompA. In silico and experimental studies were performed to compare the previously described multilocus sequence typing (MLST) schemes with our proposal. Moreover, the proposed scheme was applied (n = 68) to analyze the spatio-temporal spread of the LGV cases.ResultsOur proposal demonstrated higher diversity allowing the identification of three main groups compared to the previously published MLST based on hypervariable genes wherein only a single sequence type was identified. The temporal analysis showed that the major cluster was progressively diversifying, revealing a very active transmission chain. Furthermore, an L2b genome identical to that of the origin of the epidemic was detected, suggesting reintroductions or a low screening rate in vulnerable populations. The spatial distribution suggests that the selection and spread of new variants occurs from the central district to the peripheral regions.DiscussionThe scheme proposed in this study has proven to be useful for appropriate discrimination of LGV strains. This study, to our knowledge for the first time, demonstrates a spatio-temporal spread that increases our understanding and identifies areas with special susceptibility for maintenance of the endemic situation of LGV.

Dataset Information

Genetic variation in spatio-temporal confined USA300 community-associated MRSA isolates: a shift from clonal dispersion to genetic evolution?

Publications

Genetic variation in spatio-temporal confined USA300 community-associated MRSA isolates: a shift from clonal dispersion to genetic evolution?

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