作者: Sarah E. Anderson , Edgar X. Sherman , David S. Weiss , Philip N. Rather
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摘要: ABSTRACT Heteroresistance is a phenomenon where subpopulation of cells exhibits higher levels antibiotic resistance than the general population. Analysis tobramycin in Acinetobacter baumannii AB5075 using Etest strips demonstrated that colonies with increased arose at high frequency within zone growth inhibition. The presence resistant was confirmed by population analysis profiling (PAP). tobramycin-resistant cross to gentamicin but not amikacin. phenotype highly unstable, and reverted less frequencies 60 90% after on nonselective media. Furthermore, preincubation subinhibitory concentrations tobramycin. shown replicate during course treatment, demonstrating these were persister cells. In A. baumannii AB5075, large plasmid (p1AB5075) carries aadB, 2″-nucleotidyltransferase confers both aadB gene part an integron carried adjacent four additional genes are all flanked copies integrase gene. isolates resistance, this region amplified RecA-dependent manner. However, recA mutant, unstable mechanism did involve amplification region. These data indicate heteroresistance occurs least two mechanisms A. baumannii, future studies determine its effect patient outcomes warranted. IMPORTANCEAcinetobacter has become important pathogen hospitals worldwide, incidence infections been increasing. have exceedingly difficult treat due rapid increase multidrug- pan-resistant isolates. This prompted World Health Organization list as top priority for research development new antibiotics. study reports first time detailed aminoglycoside A. baumannii. We define mechanistic basis heteroresistance, aadB(ant2″)Ia encoding adenylyltransferase becomes Remarkably, 20 40 stochastically 1/200 cells absence selection. addition, we provide evidence second RecA-independent heteroresistance. reveals far more complex previously realized implications use aminoglycosides treating infections.