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

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 l...

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Published in:	BMC microbiology Vol. 20; no. 1; p. 288
Main Authors:	Meir, Michal, Rozenblit, Anna, Fliger, Simona, Geffen, Yuval, Barkan, Daniel
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 17-09-2020 BioMed Central BMC
Subjects:	Amides Antibacterial agents Antibiotic resistance Antibiotic tolerance Antibiotics ATP Bacteria Beta lactamases Cefazolin Clinical isolates Cloning DNA sequencing Drug resistance E coli Fitness Gene sequencing Genetic engineering Genomes Genomics Health aspects Hibernation Infection Killing curve Lactams Microbial drug resistance Mutation Nutrient dynamics Pathogens Penicillin Persistence Physiological aspects Physiology Population biology Population dynamics Protein binding Proteins Staphylococcal infections Staphylococcus aureus Staphylococcus infections Virulence Virulence (Microbiology) Whole genome sequencing β-Lactam antibiotics Persistence Killing curve Antibiotic resistance Antibiotic tolerance Staphylococcus aureus Fitness Ribosomal hibernation
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Summary:	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 (ettA ), 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. ettA and its WT counterpart were similar in their antibiotic resistance profiles to multiple antibiotics. Population dynamics of ettA 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 ettA 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2180 1471-2180
DOI:	10.1186/s12866-020-01970-w