Genetic Alternatives for Experimental Adaptation to Colistin in Three Lineages.

is characterized by a high adaptive potential, developing resistance in response to antimicrobial pressure. We employed a spatiotemporal evolution model to disclose the pathways of adaptation to colistin, a last-resort polymyxin antimicrobial, among three unrelated lineages. The ATCC-27833 reference strain (), an environmental isolate (), and a clinical isolate with multiple drug resistance () were grown over an increasing 5-step colistin concentration gradient from 0 to 400 mg/L. demonstrated the highest growth pace, achieving the 400 mg/L band in 15 days, whereas it took 37 and 60 days for and , respectively. To identify the genome changes that occurred during adaptation to colistin, the isolates selected during the growth of the bacteria ( = 185) were subjected to whole genome sequencing. In total, 17 mutation variants in eight lipopolysaccharide-synthesis-associated genes were detected. and /PA0011 were affected in all three lineages, whereas changes in were found in and but not in . In addition, mutations were detected in 34 general metabolism genes, and each lineage developed mutations in a unique set of such genes. Thus, the three examined distinct strains demonstrated different capabilities and genetic pathways of colistin adaptation.