Antibiotic heteroresistance refers to a population-wide heterogeneity in which a minor fraction of the bacterial population exhibits substantially increased resistance to certain antibiotics. Heteroresistant bacteria is capable to rapidly develop antibiotic resistance during antibiotic treatment. There are increasing evidence that post-exposure resistance from heteroresistant bacteria leads to reduced therapeutic efficacy and poor clinical outcomes, however, its development mechanism remains still unclear.
We investigated the population dynamics of tigecycline-heteroresistant Acinetobacter baumannii in the response to tigecycline treatment. Tigecycline heteroresistance was imitated via mixing a tigecycline-susceptible and -resistant A. baumannii clinical isolates (TSAB and TRAB, respectively). TRAB strain was transformed with green fluorescent protein (GFP)-carrying plasmid to distinguish from TSAB strain. As expected, the GFP signal was nearly not detected in the mimicked tigecycline-heteroresistant model, but the intensity of GFP was increased when tigecycline was treated at 1 or 2 mg/L. Tigecycline MIC of the mimicked heteroresistant model also increased from 2 to 32 mg/L, equivalent to that of TRAB strain, after tigecycline treatment. These findings indicate that resistant mutants may be derived from the pre-existing resistant subpopulations within heteroresistant bacteria.
This study was published in International Journal of Antimicrobial Agents (IF: 15.441) in April 2023 (doi: 10.1016/j.ijantimicag.2023.106739).