Reductive evolution of virulence repertoire to drive the divergence between community- and hospital-associated methicillin-resistant Staphylococcus aureus of the ST1 lineage

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) of the ST1-SCCmecIV lineage has been associated with community-acquired (CA) infections in North America and Australia. In Brazil, multidrug resistant ST1-SCCmecIV MRSA has emerged in hospital-associated (HA) diseases in Rio de Janeiro. To understand these epidemiological differences, genomic and phylogenetic analyses were performed. In addition, virulence assays were done for representative CA-and HA-MRSA strains. Despite the conservation of the virulence repertoire, some genes were missing in Brazilian ST1-SCCmecIV including lukSF-PV, fnbB, and several superantigen-encoded genes. Additionally, CA-MRSA lost the splDE while HA-MRSA strains conserved the complete operon. Most of these variable genes were located in mobile genetic elements (MGE). However, conservation and maintenance of MGEs were often observed despite the absence of their associated virulence markers. A Bayesian phylogenetic tree revealed the occurrence of more than one entrance of ST1 strains in Rio de Janeiro. The tree shape and chronology allowed us to infer that the hospitalassociated ST1-SCCmecIV from Brazil and the community-acquired USA400 from North America are not closely related and that they might have originated from different MSSA strains that independently acquired SCCmecIV cassettes. As expected, representatives of ST1 strains from Brazil showed lower cytotoxicity and a greater ability to survive inside human host cells. We suggest that Brazilian ST1-SCCmecIV strains have adapted to the hospital setting by reducing virulence and gaining the ability to persist and survive inside host cells. Possibly, these evolutionary strategies may balance the biologic cost of retaining multiple antibiotic resistance genes.

An anion and small molecule inhibition study of the β-carbonic anhydrase from Staphylococcus aureus

“…It belongs to the sadly famous ESKAPE group of bacterial pathogens ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , Enterobacter spp.) that are resistant to many clinically used antibiotics including methicillin and vancomycin 2 . As a consequence, the treatment of such infection remains particularly challenging if not impossible in severe cases 1 , 2 .…”

“…that are resistant to many clinically used antibiotics including methicillin and vancomycin 2 . As a consequence, the treatment of such infection remains particularly challenging if not impossible in severe cases 1 , 2 . Thus, there is an urgent need for new classes of antibiotics which can either inhibit the growth of these pathogens and subsequently kill them, or of compounds which can restore the sensitivity of resistant bacteria to the various classes of clinically used agents 3–5 .…”

Genomic epidemiology ofS. aureusisolated from bloodstream infections in South America during 2019 supports regional surveillance

“…Several of these clones lacked intact copies of key virulence genes such as geh/icaD/tag in MRSA-ST30, set9 in CC5-Basal, lukS/F-PV in USA300-Early branching clades or capE/selq in USA300-SAE (Figure 3-6), further supporting the added value of genomics in characterising locally circulating lineages and distinguishing them from those found in other regions/countries. This is particularly so in the light of previous work showing that absence/loss of virulence properties and the concomitant reduced toxicity could pave the way for CA clones of S. aureus to continue to cause invasive infections in the hospital environment [104][105][106][107][108]. In contrast to virulence gene loss, the sporadic acquisition of AMR determinants we observed within these CA clones could lead to the selection and expansion of new resistant clones.…”

Genomic epidemiology of Staphylococcus aureus isolated from bloodstream infections in South America during 2019 supports regional surveillance

“…This is particularly important in the light of previous work showing that absence/loss of virulence properties and the concomitant reduced toxicity could pave the way for CA clones of S. aureus to continue to cause invasive infections in the hospital environment [104–108]. In contrast to virulence gene loss, the sporadic acquisition of AMR determinants we observed within these CA clones could lead to the selection and expansion of new resistant clones.…”