Phenotypic heterogeneity in bacterial lag times and antibiotic tolerance induced by the disinfectant glutaraldehydePhenotypic heterogeneity in bacterial lag times and antibiotic tolerance induced by the disinfectant glutaraldehyde
- Phenotypic heterogeneity in clonal bacterial populations can be considered a preliminary stage of functional differentiation, which may increase population fitness in fluctuating environments. Here, we investigated how transient exposure of clonal bacterial populations to residual amounts of a commonly used disinfectant, glutaraldehyde (GTA), induces phenotypic heterogeneity, ensuring survival of the population upon sudden challenge with high doses of antibiotics. Using the ScanLag system, we found that exposure to GTA resulted in wide lag-time distributions across different bacterial isolates of E. coli, S. aureus, and P. aeruginosa. Importantly, this was associated with elevated levels of survival (i.e. tolerance) towards lethal doses of antibiotics. As revealed by RNAseq in E. coli, GTA exposure caused global transcriptome remodeling, with more than 1200 differentially expressed genes of diverse biological functions. Several of these genes that were not previously associated withPhenotypic heterogeneity in clonal bacterial populations can be considered a preliminary stage of functional differentiation, which may increase population fitness in fluctuating environments. Here, we investigated how transient exposure of clonal bacterial populations to residual amounts of a commonly used disinfectant, glutaraldehyde (GTA), induces phenotypic heterogeneity, ensuring survival of the population upon sudden challenge with high doses of antibiotics. Using the ScanLag system, we found that exposure to GTA resulted in wide lag-time distributions across different bacterial isolates of E. coli, S. aureus, and P. aeruginosa. Importantly, this was associated with elevated levels of survival (i.e. tolerance) towards lethal doses of antibiotics. As revealed by RNAseq in E. coli, GTA exposure caused global transcriptome remodeling, with more than 1200 differentially expressed genes of diverse biological functions. Several of these genes that were not previously associated with antibiotic tolerance or persistence induced, when overexpressed alone, antibiotic tolerance without showing a lag phenotype. This suggests that exposure to GTA induces unspecific, lag-dependent and specific, lag-independent tolerance to antibiotics in clonal bacterial populations. These findings have implications for 1.) settings where disinfectants and antibiotics are used in close proximity, such as hospitals and animal husbandry, and 2.) for the selection dynamics of tolerant pheno- and genotypes in fluctuating environments because of the trade-off that arises from exiting lag and resuming growth as fast as possible and maintaining antibiotic tolerance. This trade-off may be weakened by phenotypically heterogeneous clonal populations as induced by GTA.…

