Persistence against benzalkonium chloride promotes rapid evolution of tolerance during periodic disinfection

Abstract

Biocides used as disinfectants are important to prevent the transmission of pathogens, especially during the current antibiotic resistance crisis. This crisis is exacerbated by phenotypically tolerant persister subpopulations that can survive transient antibiotic treatment and facilitate resistance evolution. Here, we show that E. coli displays persistence against a widely used disinfectant, benzalkonium chloride (BAC). Periodic, persister-mediated failure of disinfection rapidly selects for BAC tolerance, which is associated with reduced cell surface charge and mutations in the lpxM locus, encoding an enzyme for lipid A biosynthesis. Moreover, the fitness cost incurred by BAC tolerance turns into a fitness benefit in the presence of antibiotics, suggesting a selective advantage of BAC-tolerant mutants in antibiotic environments. Our findings highlight the links between persistence to disinfectants and resistance evolution to antimicrobials.

Modulating the evolutionary trajectory of tolerance using antibiotics with different metabolic dependencies

“…Nonetheless, we expect the observations of differing tolerance evolution rates between SDM and WDM antibiotics to hold for any metabolism-altering mutations that lead to tolerance. While tolerance has in most cases been linked to a low metabolic state, there may be tolerance-conferring mutations that do not impact metabolic state, such as increased antibiotic efflux, in which case the evolutionary outcome may not be impacted by antibiotic metabolism dependence 59 , 60 . More work is required to understand the relationships between nhaA activity, metabolism, and antibiotic efficacy.…”

Antimicrobial Susceptibility of Persister Biofilm Cells of Bacillus cereus and Pseudomonas fluorescens

“…The tolerance development from the persistence against BAC has been the subject of other studies, as reviewed by Kampf [44]. Other authors also demonstrated the presence of phenotypically tolerant persister subpopulation to the antimicrobial activity of BAC and consequent cross-resistance to antibiotic action [45,46]. For example, Nordholt et al [45] verified an increase of BAC tolerance by Escherichia coli through reduction of cell surface charge and mutations in an enzyme for lipid A biosynthesis.…”

“…Other authors also demonstrated the presence of phenotypically tolerant persister subpopulation to the antimicrobial activity of BAC and consequent cross-resistance to antibiotic action [45,46]. For example, Nordholt et al [45] verified an increase of BAC tolerance by Escherichia coli through reduction of cell surface charge and mutations in an enzyme for lipid A biosynthesis. These features were involved in selective advantages in the presence of antibiotics [45].…”

“…For example, Nordholt et al [45] verified an increase of BAC tolerance by Escherichia coli through reduction of cell surface charge and mutations in an enzyme for lipid A biosynthesis. These features were involved in selective advantages in the presence of antibiotics [45].…”

The Federal Institute of Materials Research and Testing (BAM) – 150 Years of Enabling Scientific and Technological Breakthrough

“…I will therefore limit myself to subjectively chosen recent work that symbolically stands for societally needed and noteworthy research around environmental impact, circular economy, energy sources, and new materials. In doing so, we discover work linking antimicrobials persistence to disinfectants and the current antibiotic resistance crisis, [ 1 ] new ways of how to recover resources from industrial waste, [ 2 ] innovative analytical methods to quantify polluting per‐ and polyfluorinated alkyl substances (PFAS) in soil, [ 3 ] or how to efficiently make use of demolition waste of inorganic materials to develop and characterize new cementitious materials that reduce the high carbon footprint of Portland cement. [ 4 ] Intimately connected to reduced carbon dioxide emissions is the development of new energy materials and technologies, where current focus is given to battery research and material‐compatibility problems when using hydrogen.…”