Tolerance to Glutaraldehyde in Mediated by Overexpression of the Aldehyde Reductase YqhD by YqhC.

Glutaraldehyde is a widely used biocide on the market for about 50 years. Despite its broad application, several reports on the emergence of bacterial resistance, and occasional outbreaks caused by poorly disinfection, there is a gap of knowledge on the bacterial adaptation, tolerance, and resistance mechanisms to glutaraldehyde. Here, we analyze the effects of the independent selection of mutations in the transcriptional regulator for biological replicates of cells subjected to adaptive laboratory evolution (ALE) in the presence of glutaraldehyde. The evolved strains showed improved survival in the biocide (11-26% increase in fitness) as a result of mutations in the activator , which led to the overexpression of the aldehyde reductase gene by 8 to over 30-fold (3.1-5.2 log2FC range). The protective effect was exclusive to as other aldehyde reductase genes of , such as , , , and did not offer protection against the biocide. We describe a novel mechanism of tolerance to glutaraldehyde based on the activation of the aldehyde reductase YqhD by YqhC and bring attention to the potential for the selection of such tolerance mechanism outside the laboratory, given the existence of YqhD homologs in various pathogenic and opportunistic bacterial species.