How does population heterogeneity affect resistance to disinfectants in Mycobacterium?

ongoing

The project aims to investigate the mode-of-action of quaternary ammonium compound-based disinfectants (QACs) against Mycobacterium in comparison to the model rod-shaped bacterium, Escherichia coli. Additionally, it seeks to explore the role of phenotypic heterogeneity in the mycobacterial population’s response to disinfectant exposure. Inappropriate application of QACs may lead to the emergence of tolerance or resistance to these compounds, and possibly cross-resistance to antibiotics. Currently, there are only a few reports discussing the influence of disinfection on anti-tubercular drugs action. It is hypothesized that the specific composition of the cell wall in mycobacteria, along with the potential ability to modify this composition, and their elongation mode, contributes to high population heterogeneity, which might facilitate the adaptation to the stress imposed by QACs. To address this, the following project objectives are planned: 1) to characterize whether and how single-cell heterogeneity influences the response to QACs in rod-shaped bacteria, and 2) to elucidate the population heterogeneity-derived changes in the tolerance and resistance mechanisms of Mycobacterium against QACs. By using a fluorescently labeled analog of the commonly used benzalkonium chloride (BAC), NBD-DDA, it will be possible for the first time to conduct real-time investigations of the compound's accumulation and its effects on rod-shaped bacterial populations. The project outcome will shed light on the mechanisms underlying the emergence of tolerance and resistance to disinfectants in Mycobacterium and will help to understand the basis of potential cross-resistance between disinfectants and anti-tubercular antibiotics. Given the recent increase in disinfectant usage and the high annual incidence of mycobacterial infections, studying the potential interactions between these groups of compounds is of great importance and could guide future disinfection and treatment strategies.