Scientists decode how bacteria dodge antibiotics in hidden pockets of populations
Researchers have mapped how bacteria hide antibiotic-resistant variants within susceptible populations—a phenomenon that causes treatment failures. The finding reveals how resistance genes copy themselves under drug pressure and partially revert when antibiotics stop, opening new avenues for diagnostic tools and therapies that could outsmart bacterial evasion tactics.
Originaltitel: The dynamic distribution of genetic tandem amplifications in a heteroresistant Escherichia coli population revealed by ultra-deep long read sequencing
Abstract Antibiotic heteroresistance, characterized by rare resistant subpopulations of bacteria within a susceptible main population, is associated with treatment failure and often caused by tandem amplification of resistance genes. Here, we investigated how the distribution of tandem amplifications affects heteroresistance using an approach combining genetic engineering and ultra-deep Nanopore sequencing to accurately quantify the distribution of tandem amplification copy numbers on plasmids down to frequencies of 10 -5 . Using an Escherichia coli isolate, we describe the direct relation between the distribution of tandem amplifications increasing the copy number of a bla SHV gene and a heteroresistance phenotype to piperacillin-tazobactam, and reveal how this distribution expands under antibiotic pressure and partially reverts upon its removal. Mathematical modeling indicates that indirect resistance and fitness cost of amplifications influence the dynamic distribution of tandem amplifications. These findings provide insights into amplification-mediated phenotypes and enhance possibilities for the development of improved therapeutic and diagnostics strategies for heteroresistance.