The influence of heteroresistance, growth and antibiotic selection in shaping the invasion dynamics of colistin resistant Pseudomonas aeruginosa

Abstract

Abstract Heteroresistance, where a small subpopulation of resistant cells coexists within an otherwise susceptible population, plays a critical role in bacterial survival during antibiotic exposure. Yet, its influence on the invasion success of resistant strains remains poorly understood. In this study, we investigate the influence of bacterial heteroresistance, growth, and antibiotic selection on the outcome of an invasion experiment. We quantified the invasion dynamics of a colistin-resistant Pseudomonas aeruginosa strain across a colistin concentration gradient during co-culture with colistin-susceptible clinical P. aeruginosa isolates with varying levels of heteroresistance. The observed variation in heteroresistance and growth allowed investigation of the impact of these factors on invasion dynamics. Our results show that in antibiotic-free conditions, faster-growing isolates competitively excluded the colistin resistant invader while isolates with high levels of heteroresistance failed to do so. This competitive landscape shifted with increasing colistin concentration, giving the invader a fitness advantage that peaked around 2–4xMIC of the clinical isolate. The invasion dynamics was further influenced by the associated growth characteristics in the clinical isolates. These findings reveal how both heteroresistance and competitive exclusion shapes invasion dynamics. Understanding these interactions is critical for redesigning treatment strategies that minimize ecological opportunities for resistant strains to establish and expand.