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Evidence for clonal evolution among highly polymorphic genes in methicillin-resistant Staphylococcus aureus.

ABSTRACT: The evolution of Staphylococcus aureus has been described as predominantly clonal, based on evidence from seven housekeeping genes. We aimed to test if this was also true for more polymorphic genes. In a collection of 60 isolates including major European epidemic methicillin-resistant S. aureus (MRSA) and sporadic MRSA strains, we compared the partial gene sequences of seven housekeeping genes (arcC, aroE, glpF, gmk, pta, tpi, and yqiL), six core adhesion genes (present in all strains) (clfA, clfB, fnbA, map, sdrC, and spa), and four accessory adhesion genes (not present in all strains) (ebpS, fnbB, sdrD, and sdrE). Nucleotide diversity of adhesion genes was 2- to 10-fold higher than genes used for multilocus sequence typing. All genes showed evidence for purifying selection with a weakly reduced level among accessory adhesion genes. Among these highly variable genes, there was no evidence for a difference in molecular evolution between epidemic and sporadic strains. Gene trees constructed from concatenated sequences of housekeeping, core adhesion, and accessory adhesion genes were highly congruent, indicating clonality, despite some evidence for homologous exchange. Further evidence for clonality was found with an overall positive correlation of allelic and nucleotidic divergence for both seven housekeeping genes and six core adhesion genes. However, for small allelic differences that fit the demarcations of clonal complexes (CCs) there was no such correlation, suggesting that recombination occurred. Therefore, despite an overall clonal population structure, recombination between related isolates within CCs might have contributed to S. aureus evolution.

SUBMITTER: Kuhn G

PROVIDER: S-EPMC1317586 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature

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Evidence for clonal evolution among highly polymorphic genes in methicillin-resistant Staphylococcus aureus.

Kuhn G G Francioli P P Blanc D S DS

Journal of bacteriology 20060101 1

The evolution of Staphylococcus aureus has been described as predominantly clonal, based on evidence from seven housekeeping genes. We aimed to test if this was also true for more polymorphic genes. In a collection of 60 isolates including major European epidemic methicillin-resistant S. aureus (MRSA) and sporadic MRSA strains, we compared the partial gene sequences of seven housekeeping genes (arcC, aroE, glpF, gmk, pta, tpi, and yqiL), six core adhesion genes (present in all strains) (clfA, cl ...[more]

PMID: 16352833

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Project description:Since the late 1990s, changes in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) were recognized with the emergence of community-associated MRSA (CA-MRSA). CA-MRSA belonging to clonal complex 152 (CC152), carrying the small staphylococcal cassette chromosome mec (SCCmec) type V and encoding the Panton-Valentine leukocidin (PVL), has been observed in Europe. The aim of this study was to investigate its origin, evolution, and dissemination. Whole-genome sequencing was performed on a global collection of 149 CC152 isolates spanning 20 years (93 methicillin-susceptible S. aureus [MSSA] and 56 MRSA isolates). Core genome phylogeny, Bayesian inference, in silico resistance analyses, and genomic characterization were applied. Phylogenetic analysis revealed two major distinct clades, one dominated by MSSA and the other populated only by MRSA. The MSSA isolates were predominately from sub-Saharan Africa, whereas MRSA was almost exclusively from Europe. The European MRSA isolates all harbored an SCCmec type V (5C2&5) element, whereas other SCCmec elements were sporadically detected in MRSA from the otherwise MSSA-dominated clade, including SCCmec types IV (2B), V (5C2), and XIII (9A). In total, 93% of the studied CC152 isolates were PVL positive. Bayesian coalescent inference suggests an emergence of the European CC152-MRSA in the 1990s, while the CC152 lineage dates back to the 1970s. The CA-MRSA CC152 clone mimics the European CC80 CA-MRSA lineage by its emergence from a PVL-positive MSSA ancestor from North Africa or Europe. The CC152 lineage has acquired SCCmec several times, but acquisition of SCCmec type V (5C2&5) seems associated with expansion of MRSA CC152 in Europe.IMPORTANCE Understanding the evolution of CA-MRSA is important in light of the increasing importance of this reservoir in the dissemination of MRSA. Here, we highlight the story of the CA-MRSA CC152 lineage using whole-genome sequencing on an international collection of CC152. We show that the evolution of this lineage is novel and that antibiotic usage may have the potential to select for the phage-encoded Panton-Valentine leukocidin. The diversity of the strains correlated highly to geography, with higher level of resistance observed among the European MRSA isolates. The mobility of the SCCmec element is mandatory for the emergence of novel MRSA lineages, and we show here distinct acquisitions, one of which is linked to the successful clone found throughout Europe today.

Project description:ObjectivesEpidemic methicillin-resistant S. aureus (MRSA) clones cause infections in both hospital and community settings. As a biofilm phenotype further facilitates evasion of the host immune system and antibiotics, we compared the biofilm-forming capacities of various MRSA clones.MethodsSeventy-six MRSA classified into 13 clones (USA300, EMRSA-15, Hungarian/Brazilian etc.), and isolated from infections or from carriers were studied for biofilm formation under static and dynamic conditions. Static biofilms in microtitre plates were quantified colorimetrically. Dynamic biofilms (Bioflux 200, Fluxion, USA) were studied by confocal laser-scanning and time-lapse microscopy, and the total volume occupied by live/dead bacteria quantified by Volocity 5.4.1 (Improvision, UK).ResultsMRSA harbouring SCCmec IV produced significantly more biomass under static conditions than SCCmec I-III (P = 0.003), and those harbouring SCCmec II significantly less than those harbouring SCCmec I or III (P<0.001). In the dynamic model, SCCmec I-III harbouring MRSA were significantly better biofilm formers than SCCmec IV (P = 0.036). Only 16 strains successfully formed biofilms under both conditions, of which 13 harboured SCCmec IV and included all tested USA300 strains (n = 3). However, USA300 demonstrated remarkably lower percentages of cell-occupied space (6.6%) compared to the other clones (EMRSA-15 = 19.0%) under dynamic conditions. Time-lapse microscopy of dynamic biofilms demonstrated that USA300 formed long viscoelastic tethers that stretched far from the point of attachment, while EMRSA-15 consisted of micro-colonies attached densely to the surface.ConclusionsMRSA harbouring SCCmec types IV and I-III demonstrate distinct biofilm forming capacities, possibly owing to their adaptation to the community and hospital settings, respectively. USA300 demonstrated abundant biofilm formation under both conditions, which probably confers a competitive advantage, contributing to its remarkable success as a pathogen.

Project description:Clonal complex 5 methicillin-resistant Staphylococcus aureus (CC5-MRSA) includes multiple prevalent clones that cause hospital-associated infections in the Western Hemisphere. Here, we present a phylogenomic study of these MRSA to reveal their phylogeny, spatial and temporal population structure, and the evolution of selected traits. We studied 598 genome sequences, including 409 newly generated sequences, from 11 countries in Central, North, and South America, and references from Asia and Europe. An early-branching CC5-Basal clade is well-dispersed geographically, is methicillin-susceptible and MRSA predominantly of ST5-IV such as the USA800 clone, and includes separate subclades for avian and porcine strains. In the early 1970s and early 1960s, respectively, two clades appeared that subsequently underwent major expansions in the Western Hemisphere: a CC5-I clade in South America and a CC5-II clade largely in Central and North America. The CC5-I clade includes the ST5-I Chilean/Cordobes clone, and the ST228-I South German clone as an early offshoot, but is distinct from other ST5-I clones from Europe that nest within CC5-Basal. The CC5-II clade includes divergent strains of the ST5-II USA100 clone, various other clones, and most known vancomycin-resistant strains of S. aureus, but is distinct from ST5-II strain N315 from Japan that nests within CC5-Basal. The recombination rate of CC5 was much lower than has been reported for other S. aureus genetic backgrounds, which indicates that recurrence of vancomycin resistance in CC5 is not likely due to an enhanced promiscuity. An increased number of antibiotic resistances and decreased number of toxins with distance from the CC5 tree root were observed. Of note, the expansions of the CC5-I and CC5-II clades in the Western Hemisphere were preceded by convergent gains of resistance to fluoroquinolone, macrolide, and lincosamide antibiotics, and convergent losses of the staphylococcal enterotoxin p (sep) gene from the immune evasion gene cluster of phage ϕSa3. Unique losses of surface proteins were also noted for these two clades. In summary, our study has determined the relationships of different clades and clones of CC5 and has revealed genomic changes for increased antibiotic resistance and decreased virulence associated with the expansions of these MRSA in the Western Hemisphere.

Project description:UNLABELLED:Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations. IMPORTANCE:With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.

Project description:Staphylococcus aureus causes a variety of debilitating and life-threatening diseases, and thus remains a challenging global health threat. S. aureus is remarkably diverse, yet only a minority of methicillin-resistant S. aureus (MRSA) clones have caused pandemic proportions of diseases. The genetic drivers of the successful dissemination of some clones across wide geographical expanses remain poorly understood. We analyzed 386 recently published MRSA genomes from bloodstream infections sampled in North, Central, and South America from 2011 to 2018. Here, we show that MRSA-associated bloodstream infections were attributable to two genetically distinct lineages. One lineage consisted almost exclusively of sequence type (ST) 8, which emerged in 1964. A second lineage emerged in 1986 and consisted of STs 5, 105, and 231. The two lineages have simultaneously disseminated across geographically distant sites. Sublineages rapidly diverged within locations in the early 2000s. Their diversification was associated with independent acquisitions of unique variants of the mobile mecA-carrying chromosomal cassette and distinct repertoires of antimicrobial resistance genes. We show that the evolution and spread of invasive multidrug-resistant MRSA in the Americas was driven by transcontinental dissemination, followed by more recent establishment and divergence of local pathogen populations. Our study highlights the need for continued international surveillance of high-risk clones to control the global health threat of multidrug resistance. IMPORTANCE Bloodstream infections due to S. aureus cause significant patient morbidity and mortality worldwide, exacerbated by the emergence and spread of methicillin resistant S. aureus (MRSA). This study provides important insights on the evolution and long-distance geographic expansion of two distinct MRSA lineages that predominate in bloodstream infections in the past 5 decades. The success of these two lineages partly lies on their acquisition of a diverse set of antimicrobial resistance genes and of unique variants of the mobile genetic element SCCmec that carries the gene mecA conferring resistance to beta-lactams. High-risk antimicrobial resistant clones can therefore rapidly disseminate across long distances and establish within local communities within a short period of time. These results have important implications for global initiatives and local epidemiological efforts to monitor and control invasive MRSA infections and transcontinental spread of multidrug resistance.

Dataset Information

Evidence for clonal evolution among highly polymorphic genes in methicillin-resistant Staphylococcus aureus.

Publications

Evidence for clonal evolution among highly polymorphic genes in methicillin-resistant Staphylococcus aureus.

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