Molecular insights into disinfectant resistance of a highly resistant 𝘚𝘦𝘳𝘳𝘢𝘵𝘪𝘢 species

Abstract

Antimicrobial resistance (AMR) is a global crisis, and with fewer antibiotics entering the market, disinfectant resistance poses an emerging threat. This dissertation investigates the mechanisms of high Quaternary Ammonium Compound (QAC) resistance in 𝘚𝘦𝘳𝘳𝘢𝘵𝘪𝘢 sp. HRI. This work identified multiple resistance mechanisms, focusing on the stress response as a key regulator. In Chapter 1, a signature transcriptomic profile of benzalkonium chloride (BC) was generated by reviewing available literature on the transcriptomic response of several bacteria to BC. The transcriptomic response of bacteria to BC exposed minimal correlation with known QAC resistance mechanisms, suggesting novel pathways. Chapter 2 revealed a hormetic effect in which sub-MIC levels of disinfectants stimulated bacterial growth, potentially increasing infection risks. Chapter 3 observed no biofilm formation but identified outer membrane vesicles (OMVs) in the resistant isolate, suggesting OMVs contribute to QAC resistance, potentially acting as a barrier similar to their role in antibiotic resistance. Further analysis in Chapters 4 and 5, revealed up-regulation of an uncharacterised MFS pump and polyamine synthesis pathways, both involved in disinfectant resistance through efflux mechanisms. Differential gene expression indicated that efflux pumps and stress response systems act in tandem to confer resistance. Susceptibility tests confirmed the role of the stress response in increasing QAC resistance in 𝘚𝘦𝘳𝘳𝘢𝘵𝘪𝘢 sp. HRI. Overall, this research highlights the complex, multifaceted nature of disinfectant resistance, proposing that the stress response regulates various resistance mechanisms, including efflux pumps and OMVs. This study offers new insights into disinfectant resistance, suggesting that future strategies should focus on understanding and mitigating the stress response to preserve the efficacy of disinfectants.