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Genomic Epidemiology of CC30 Methicillin-Resistant Staphylococcus aureus Strains from Argentina Reveals Four Major Clades with Distinctive Genetic Features.

ABSTRACT: Staphylococcus aureus clonal complex 30 (CC30) has given rise to epidemics worldwide and is one of the most prevalent lineages in Argentina, represented by sequence type 30 methicillin-resistant S. aureus SCCmec type IV (ST30-MRSA-IV). ST30-MRSA-IV has displaced previous prevalent clones in the country and demonstrated increased virulence. Despite the burden of infections caused by ST30-MRSA-IV both in hospitals and in communities in Argentina, no detailed genome-based characterization of this clone is available to date. In this study, we used whole-genome sequencing (WGS) to evaluate the genetic diversity, population structure, and genomic characteristics of 190 CC30-MRSA strains circulating in Argentina between 2004 and 2015. Phylogenetic analysis revealed the existence of 4 major clades: ARG-1 (CC30-MRSA-IVc-spa t012), ARG-2 (ST30-MRSA-IVc-spa t021 related), ARG-3 (ST30-MRSA-IVh/j-spa t021 and related), and ARG-4 (CC30-MRSA-IVc-spa t019 and related). The clades were characterized by different distributions of antimicrobial resistance determinants, virulence genes, and mobile genetic elements (MGEs). While ARG-1 and ARG-4 were related to global epidemic MRSA-16 (EMRSA-16) and South West Pacific (SWP) clones, respectively, ARG-3 was phylogenetically distinct from previously defined CC30 epidemic clones. ARG-4, the most prevalent and geographically disseminated in the collection (N = 164), was characterized by specific MGEs and chromosomal mutations that might have contributed to its virulence and success. To our knowledge, this is the first genomic epidemiology study of CC30-MRSA in Argentina, which will serve as baseline genomic data going forward to inform public health measures for infection prevention and control.IMPORTANCE The rise in prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is of public health concern. In Argentina, several studies documented a shift in the epidemiology of CA-MRSA since 2009, with clonal complex 30 (CC30) and, in particular, sequence type 30 MRSA SCCmec type IV (ST30-MRSA-IV) replacing other clones both in communities and in hospitals and possibly displaying increased virulence. By sequencing the whole genomes of 190 CC30 MRSA isolates recovered from Argentina between 2005 and 2015, we showed that they represented a diverse population composed of 4 major clades. The predominant clade evolved from the South West Pacific clone but has acquired a distinct repertoire of mobile genetic elements, virulence genes, and chromosomal mutations that might play a role in its success. Our work is the first extensive genomic study of CC30 S. aureus in Argentina and will contribute not only to the development of genomic surveillance in the region but also to our understanding of the global epidemiology of this pathogen.

SUBMITTER: Di Gregorio S

PROVIDER: S-EPMC8546718 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Staphylococcus pseudintermedius is the leading cause of pyoderma in dogs and the frequent use of antimicrobial treatment is associated to the development of resistance to nearly all classes of antibiotics. Despite S. pseudintermedius significance, our understanding of the molecular mechanism of ?-lactam resistance and its genetic diversity remains limited. We aimed to: i) determine the phenotypic resistance profile of methicillin resistant Staphylococcus pseudintermedius (MRSP) isolated from infected dogs in three different veterinary hospitals in Buenos Aires, Argentina; ii) identify the SCCmec elements and resistance genes; and iii) analyze the clonal relationship between isolates and in regard of dominant lineages found in the world. RESULTS:In addition to the differential levels of ?-lactam resistance, MRSP isolates (n?=?10) showed resistance to 5-6 families of antibiotics, and were therefore categorized as multidrug-resistant. All the isolates were variant of SCCmec V homologous to S. aureus; additional SCCmecFinder analysis classified five of the genomes as SCCmec type V (5C2&5) with mecA (encodes for PBP2a), mecRI and mecI and all the genes closely related to the reference SCCmec type V S. aureus TSGH17 strain. In the remaining five strains, mecA was present, although other genes associated with SCCmec V including mecR1 and mecI were missing. PBP2a was inducible in low level resistance strains (MRSP 8151), and constitutively expressed in MRSP 8150, suggesting different mecA regulatory mechanisms. MRSP isolates showed significant genetic diversity: eight PFGE clonal types and six multilocus-sequence typing (MLST) sequence types (STs) (339, 649, 919, 920, 921 and 922), including four new STs genetically distinct from STs reported in other geographic areas. Comparative genomics and phylogenetic analyses of the MRSP showed a correlation between the genetic content and the phenotypes, and established the genetic relationship between the isolates. CONCLUSIONS:MRSP could be a threat to animal health due to it concerning level of antimicrobial resistance. Our study highlights genetic and epidemiological aspects of multidrug-resistant MRSP strains from Argentina showing high degree of correlation between the resistance genes and the phenotype of the isolates and, furthermore, they appeared evolutionary closer to major worldwide reported ST68 and ST71.

Project description:BackgroundBloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.MethodsWe generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010-2018.ResultsIn silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams and macrolides being the most prevalent. The most common resistance genes were blaZ and mecA, which were found in 262/323 (81.11%) and 104/323 (32.20%) isolates, respectively. Majority of the MRSA (102/105 isolates or 97.14%) identified using in vitro screening were related to two clonal complexes (CC) 5 and 8. The two CCs emerged in the New Hampshire population at separate times. We estimated that the time to the most recent common ancestor of CC5 was 1973 (95% highest posterior density (HPD) intervals: 1966-1979) and 1946 for CC8 (95% HPD intervals: 1924-1959). The effective population size of CC8 increased until the late 1960s when it started to level off until late 2000s. The levelling off of CC8 in 1968 coincided with the acquisition of SCCmec Type IV in majority of the strains. The plateau in CC8 also coincided with the acceleration in the population growth of CC5 carrying SCCmec Type II in the early 1970s, which eventually leveled off in the early 1990s. Lastly, we found evidence for frequent recombination in the two clones during their recent clonal expansion, which has likely contributed to their success in the population.ConclusionsWe conclude that the S. aureus population was shaped mainly by the clonal expansion, recombination and co-dominance of two major MRSA clones in the last five decades in New Hampshire, USA. These results have important implications on the development of effective and robust strategies for intervention, control and treatment of life-threatening bloodstream infections.

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Genomic Epidemiology of CC30 Methicillin-Resistant Staphylococcus aureus Strains from Argentina Reveals Four Major Clades with Distinctive Genetic Features.

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