The emergence of the human skin colonizer Staphylococcus epidermidis as a pathogen related to medical devices-associated infections occurred relatively recently. However, how the pressure of the nosocomial setting drove S. epidermidis evolution, remains to be clarified. To identify the genomic events associated with the evolutionary history of S. epidermidis we compared the genome of nosocomial S. epidermidis from before the time they were recognized as human pathogens (1960s), with those from 1990s when they were already a frequent cause of infections in hospitals. We found that the early and contemporary S. epidermidis had common and distinctive features. They shared the same genetic background, both belonging mainly to the major clonal lineage CC2 (67% and 79%, respectively), they could carry a multidrug resistance profile and harboured several virulence factors. Isolates collected in the 1960s, carried antibiotic resistance genes for at least 8 antibiotic classes, namely, aminoglycosides, (aaD, 9.5%) macrolides (ermA, 9.5%), fusidic acid (fusB, 9.5%), tetracycline (tet(K), 14.3%); chloramphenicol cat, 14.3%; penicillin (blaZ, 67%), fluoroquinolones (norA, 100%), and fosfomycin (fosA, 100%). A single early isolate carried mecA, disrupted by IS431, within a staphylococcal cassette chromosome mec (SCCmec) IV-like element. Early strains also carried multiple virulence factors, namely biofilm-associated genes (ica 5%; aap 38%, atlE 100%), genes encoding cell wall anchored proteins (sdrH 100%, sdrG 100%), lipases (geh-1 100%, geh-2 100%), and capsular proteins (cap 100%) as well as the arginine catabolic mobile element (ACME I and II, 38% each). Additionally, their genome contained numerous (>8 copies) and diverse insertion sequences (IS) and prophages (95%). On the other hand contemporary strains, were enriched in genes providing resistance to antibiotics, including beta-lactams (SCCmec IV, 57%; blaZ, 100%), aminoglycosides (aac(6')-aph(2''), 19%); macrolides (ermC, 14%), fusidic acid (fusB, 43%) and tetracyclines (tet(L), 5%); and virulence, namely biofilm-associated genes (bap, 7%; sdrF, 14%; ica, 21%; and aap, 64%) and ACME-I (57%). Moreover, contemporary strains carried IS256 and a significant lower number of prophages (50%).Our results showed that the continued exposure of S. epidermidis to hospital environment led to accumulation of genes associated to antibiotic resistance, colonization, biofilm formation, genome plasticity and to phage loss what might have contributed to its success as a pathogen.
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