AUTHOR=Asante Jonathan , Hetsa Bakoena A. , Amoako Daniel G. , Abia Akebe L. K. , Bester Linda A. , Essack Sabiha Y. TITLE=Genomic Analysis of Antibiotic-Resistant Staphylococcus epidermidis Isolates From Clinical Sources in the Kwazulu-Natal Province, South Africa JOURNAL=Frontiers in Microbiology VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.656306 DOI=10.3389/fmicb.2021.656306 ISSN=1664-302X ABSTRACT=Staphylococcus epidermidis has become an important nosocomial pathogen. Methicillin and multidrug resistance make S. epidermidis infections difficult to treat. The study aims to describe the genomic characteristics of methicillin-resistant S. epidermidis (MRSE) isolated from clinical sources, to comprehend the genetic basis of antibiotic resistance, virulence and potential pathogenicity. Sixteen methicillin-resistant S. epidermidis (MRSE) were characterized by whole-genome sequencing and bioinformatics analysis to ascertain their resistome, virulome, mobilome, clonality and phylogenomic relationships. In all, 75% of isolates displayed multidrug resistance and were associated with the carriage of multiple resistance genes including mecA, blaZ, tet(K), erm(A), erm(B), erm(C), dfrG, aac(6')-aph(2'') and cat(pC221) conferring resistance to β-lactams, tetracyclines, macrolide-lincosamide-streptogramin B, aminoglycosides and phenicols, that were located on both plasmids and chromosomes. Their virulence profile evidenced genes involved in adherence/biofilm formation (icaA, icaB, icaC, atl, ebh, ebp), immune evasion (adsA, capC, manA) and antiphagocytosis (rmlC, cdsA, cpsA). The community-acquired SCCmec_type_IV was the most common SCCmec type. The CoNS belonged to seven multilocus sequence types (MLSTs) and carried a diversity of mobile genetic elements such as phages, insertion sequences and plasmids. The bacterial anti-phage defense systems CRISPR-Cas immunity phage system and Restriction-Modification System (R-M system) and the Arginine Catabolic Mobile Element (ACME) involved in immune evasion and transport of virulence genes were also found. The insertion sequence, IS256, linked with virulence, was found in 56.3% of isolates. Isolates were organized into two major clades with some similarity but also considerable variability within isolates. Whole-genome sequencing and bioinformatics analysis provide insights into the likely pathogenicity and antibiotic resistance of S. epidermidis, necessitating surveillance of this emerging pathogen.