EttA is likely non-essential in Staphylococcus aureus persistence, fitness or resistance to antibiotics

BMC Microbiology

article

Meir, Michal¹  Rozenblit, Anna²  Fliger, Simona²  Geffen, Yuval³  Barkan, Daniel² 

[1] The Ruth Rappaport Children’s Hospital, Rambam Health Care Campus;Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, The Hebrew University of Jerusalem;Clinical Microbiology Laboratory, Rambam Health Care Campus

关键词: Staphylococcus aureus;    Antibiotic resistance;    Antibiotic tolerance;    Persistence;    Fitness;    Killing curve;    Ribosomal hibernation;   

DOI  :  10.1186/s12866-020-01970-w

学科分类：放射科、核医学、医学影像

来源: BioMed Central

【 摘 要 】

Tolerance to antibiotics and persistence are associated with antibiotic treatment failures, chronic-relapsing infections, and emerging antibiotic resistance in various bacteria, including Staphylococcus aureus. Mechanisms of persistence are largely unknown, yet have been linked to physiology under low-ATP conditions and the metabolic-inactive state. EttA is an ATP-binding cassette protein, linked in Eschrechia coli to ribosomal hibernation and fitness in stationary growth phase, yet its role in S. aureus physiology is unknown. Using whole genome sequencing (WGS) of serial clinical isolates, we identified an EttA-negative S. aureus mutant (ettAstop), and its isogenic wild-type counterpart. We used these two isogenic clones to investigate the role of ettA in S. aureus physiology in starvation and antibiotic stress, and test its role in persistence and antibiotic tolerance. ettAstop and its WT counterpart were similar in their antibiotic resistance profiles to multiple antibiotics. Population dynamics of ettAstop and the WT were similar in low-nutrient setting, with similar recovery from stationary growth phase or starvation. Supra-bacteriocidal concentration of cefazolin had the same killing effect on ettAstop and WT populations, with no difference in persister formation. Lack of ettA does not affect S. aureus antibiotic resistance, beta-lactam tolerance, resilience to starvation or fitness following starvation. We conclude the role of ettA in S. aureus physiology is limited or redundant with another, unidentified gene. WGS of serial clinical isolates may enable investigation of other single genes involved in S. aureus virulence, and specifically persister cell formation.

【 授权许可】

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