RT Journal Article
SR Electronic
T1 Environmental conditions dictate differential evolution of vancomycin resistance in <em>Staphylococcus aureus</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.07.138933
DO 10.1101/2020.06.07.138933
A1 Machado, Henrique
A1 Seif, Yara
A1 Sakoulas, George
A1 Olson, Connor A.
A1 Szubin, Richard
A1 Palsson, Bernhard O.
A1 Nizet, Victor
A1 Feist, Adam M.
YR 2020
UL http://biorxiv.org/content/early/2020/06/07/2020.06.07.138933.abstract
AB While microbiological resistance to vancomycin in Staphylococcus aureus is rare, clinical vancomycin treatment failures are common, and methicillin-resistant S. aureus (MRSA) strains isolated from patients after prolonged vancomycin treatment failure remain susceptible. Adaptive laboratory evolution was utilized to uncover mutational mechanisms associated with MRSA vancomycin resistance in a bacteriological medium used in clinical susceptibility testing and a physiological medium. Sequencing of resistant clones revealed shared and media-specific mutational outcomes, with an overlap in cell wall regulons (walKRyycHI, vraSRT). Evolved strains displayed similar genetic and phenotypic traits to resistant clinical isolates. Importantly, resistant phenotypes that developed in physiological media did not translate into resistance in bacteriological media. Further, a bacteriological media-specific mechanism for vancomycin resistance enabled by a mutated mprF was confirmed. This study bridges the gap of understanding between clinical and microbiological vancomycin resistance in S. aureus and expands the number of allelic variants that result in vancomycin resistance phenotypes.