Abstract
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 yqhC for biological replicates of Escherichia coli 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 yqhC, which led to the overexpression of the yqhD aldehyde reductase gene by 8 to over 30-fold (3.1–5.2 log2FC range). The protective effect was exclusive to yqhD as other aldehyde reductase genes of E. coli, such as yahK, ybbO, yghA, and ahr 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.
Highlights
Glutaraldehyde (1,5 pentanedial) is a biocide that has been commercialized for about 50 years, with broad activity against bacteria, mycobacteria, fungi, viruses, and spores (Russell, 1994)
Despite the additional mutations in all the three glutaraldehyde-evolved strains, the independent selection for yqhC mutations in multiple replicates after exposure to glutaraldehyde suggested a primary role of yqhC in such an environment
Our results suggested a role of yqhD, but not dkgA, for the survival of E. coli cells in minimal media in the presence of glutaraldehyde
Summary
Glutaraldehyde (1,5 pentanedial) is a biocide that has been commercialized for about 50 years, with broad activity against bacteria, mycobacteria, fungi, viruses, and spores (Russell, 1994). The disinfectant has been widely used in the cosmetic, food, poultry, leather industries, water treatment systems, dentistry, and hospitals (Simões et al, 2011; Vikram et al, 2015). Marketed with name brands such as Glutaral and Cidex, the biocide is commonly used to disinfect medical instruments, especially heat-sensitive, such as flexible and other heat-sensitive endoscopes (Griffiths et al, 1997). Other aldehydes used for disinfection in hospitals include formaldehyde and ortho-phthalaldehyde (Abreu et al, 2013). The mechanism of action of glutaraldehyde in the cells is believed to be through its cross-linking interaction with amino groups of proteins (Russell, 1994).
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