Short- and Long-Term Transcriptomic Responses of Escherichia coli to Biocides: a Systems Analysis

The mechanisms of the bacterial response to biocides are poorly understood, despite their broad application. To identify the genetic basis and pathways implicated in the biocide stress response, we exposed Escherichia coli populations to 10 ubiquitous biocides. By comparing the transcriptional responses between a short-term exposure (30 min) and a long-term exposure (8 to 12 h) to biocide stress, we established the common gene and pathway clusters that are implicated in general and biocide-specific stress responses. Our analysis revealed a temporal choreography, starting from the upregulation of chaperones to the subsequent repression of motility and chemotaxis pathways and the induction of an anaerobic pool of enzymes and biofilm regulators. A systematic analysis of the transcriptional data identified a zur-regulated gene cluster to be highly active in the stress response against sodium hypochlorite and peracetic acid, presenting a link between the biocide stress response and zinc homeostasis. Susceptibility assays with knockout mutants further validated our findings and provide clear targets for downstream investigation of the implicated mechanisms of action. IMPORTANCE Antiseptics and disinfectant products are of great importance to control and eliminate pathogens, especially in settings such as hospitals and the food industry. Such products are widely distributed and frequently poorly regulated. Occasional outbreaks have been associated with microbes resistant to such compounds, and researchers have indicated potential cross-resistance with antibiotics. Despite that, there are many gaps in knowledge about the bacterial stress response and the mechanisms of microbial resistance to antiseptics and disinfectants. We investigated the stress response of the bacterium Escherichia coli to 10 common disinfectant and antiseptic chemicals to shed light on the potential mechanisms of tolerance to such compounds.