Evolution of Multi-Resistance to Vancomycin, Daptomycin, and Linezolid in Methicillin-Resistant Staphylococcus aureus Causing Persistent Bacteremia.

摘要: The genomic evolution in vivo persistent infection was critical information for understanding how methicillin-resistant Staphylococcus aureus (MRSA) adapted to host environments with high antibiotic selective pressure. Thirty-two successive MRSA blood isolates incremental non-susceptibility vancomycin (VISA), daptomycin (DRSA), and/or linezolid (LRSA) were isolated from a patient failing multiple courses of antimicrobial therapy during 1,356 days bacteremia. Whole genome sequencing (WGS) all consecutive conducted characterize the evolutionary pathways, resistance-associated mutations and their temporal relationship treatment. WGS-based phylogeny categorized isogenic strains into three major clades, I (22 isolates), II (7 III (3 respectively, harboring median (range) 7 (1-30), 62 (53-65), 118 (100-130) non-synonymous when compared very first isolate. Clade further grouped early late subclades, which, shared most recent common ancestor at day 393.7 strain 662.5. characterized, rates VISA (9/22, 40.9%) VISA-and-DRSA phenotype (2/3, 66.7%). Linezolid-resistance including VISA-DRSA-and-LRSA exclusively identified after eight LRSA displayed small colony variant associated G2576T domain V region 23S rRNA. Substantial loss mobile elements or alleles mediating resistance virulence multi-resistance. However, gene might not be correlated development VISA, DRSA, phenotype. In conclusion, bacteremia harsh environment through pathways involving both extensive loss.