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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.

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The emergence of vancomycin intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) is of major concern worldwide. Our objective was to investigate the prevalence, phenotypic and molecular features of hVISA strains isolated from bacteremic patients and to determine the clinical significance of the hVISA phenotype in patients with bacteremia. A total of 104 S. aureus blood isolates were collected from a teaching hospital of Argentina between August 2009 and November 2010. No VISA isolate was recovered, and 3 out of 92 patients (3.3%) were infected with hVISA, 2 of them methicillin-resistant S. aureus (MRSA) (4.5% of MRSA). Macro Etest and prediffusion method detected 3/3 and 2/3 hVISA respectively. Considering the type of bacteremia, the three cases were distributed as follows: two patients had suffered multiple episodes of bacteremia (both hVISA strains recovered in the second episode), while only one patient had suffered a single episode of bacteremia with hVISA infection. MRSA bloodstream isolates exhibiting the hVISA phenotype were related to HA-MRSA Cordobes clone (ST5-SCCmec I-spa t149) and MRSA Argentinean pediatric clone (ST100-SCCmec IVNV-spa t002), but not to CA-MRSA-ST30-SCCmec IV-spa t019 clone that was one of the most frequent in our country. Although still relatively infrequent in our hospital, hVISA strains were significantly associated with multiple episodes of bacteremia (p=0.037) and genetically unrelated.

Staphylococcus aureus chronic airway infection in patients with cystic fibrosis (CF) allows this pathogen to adapt over time in response to different selection pressures. We have previously shown that the main sequence types related to community-acquired methicillin-resistant S. aureus (MRSA) infections in Argentina – ST5 and ST30 – are also frequently isolated from the sputum of patients with CF, but in these patients they usually display multi-drug antimicrobial resistance. In this study, we sequenced the genomes of MRSA from four paediatric CF patients with the goal of identifying mutations among sequential isolates, especially those possibly related to antimicrobial resistance and virulence, which might contribute to the adaptation of the pathogen in the airways of patients with CF. Our results revealed genetic differences in sequential MRSA strains isolated from patients with CF in both their core and accessory genomes. Although the genetic adaptation of S. aureus was distinct in different hosts, we detected independent mutations in thyA, htrA, rpsJ and gyrA – which are known to have crucial roles in S. aureus virulence and antimicrobial resistance – in isolates recovered from multiple patients. Moreover, we identified allelic variants that were detected in all of the isolates recovered after a certain time point; these non-synonymous mutations were in genes associated with antimicrobial resistance, virulence, iron scavenging and oxidative stress resistance. In conclusion, our results provide evidence of genetic variability among sequential MRSA isolates that could be implicated in the adaptation of these strains during chronic CF airway infection.

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Staphylococcus aureus remains one of the leading causes of infections worldwide and a common cause of bacteraemia. However, studies documenting the epidemiology of S. aureus in South America using genomics are scarce. We hereby report on the largest genomic epidemiology study to date of both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in South America, conducted by the StaphNET-SA network. We characterised 404 genomes recovered from a prospective observational study of S. aureus bacteraemia in 58 hospitals from Argentina, Bolivia, Brazil, Paraguay and Uruguay between April and October 2019. We show that a minority of S. aureus isolates are phenotypically multi-drug resistant (5.2%), but more than a quarter are resistant to macrolide–lincosamide–streptogramin B (MLSb). MSSA were more genetically diverse than MRSA. Lower rates of associated antimicrobial resistance in community-associated(CA)-MRSA versus hospital-associated (HA)-MRSA were found in association with three S. aureus genotypes dominating the MRSA population: CC30-MRSA-IVc-t019-lukS/F-PV+, CC5-MRSA-IV-t002-lukS/F-PV- and CC8-MRSA-IVc-t008-lukS/F-PV+-COMER+. These are historically from a CA origin, carry on average fewer antimicrobial resistance determinants, and often lack key virulence genes. Surprisingly, CC398-MSSA-t1451-lukS/F-PV- related to the CC398 human-associated lineage is widely disseminated throughout the region, and is described here for the first time as the most prevalent MSSA lineage in South America. Moreover, CC398 strains carrying ermT (largely responsible for the MLSb resistance rates of MSSA strains: inducible iMLSb phenotype) and sh_fabI (related to triclosan resistance) were recovered from both CA and HA origin. The frequency of MRSA and MSSA lineages differed between countries but the most prevalent S. aureus genotypes are high-risk clones widely distributed in the South American region without a clear country-specific phylogeographical structure. Therefore, our findings underline the need for continuous genomic surveillance by regional networks such as StaphNET-SA. This article contains data hosted by Microreact.