Influence of Structurally Distinct Cationic Biocides on Antimicrobial Resistance Development and Virulence in Pseudomonas aeruginosa Public
Vargas-Cuebas, Germán G. (Fall 2024)
Abstract
Cationic biocides are an essential component in our arsenal against infectious agents. Their presence is ubiquitous in our lives, from biocides used in the food industry as preservatives, to those used for disinfection of biotic and abiotic surfaces in households and clinical settings. My dissertation work focused on two classes of cationic biocide: quaternary ammonium compounds (QACs) and quaternary phosphonium compounds (QPCs).
QACs are a class of cationic biocide commonly found as active ingredients in disinfectants and antiseptics. However, despite their widespread use and abundant production, commercially available QACs lack structural diversity, leading to concerns of ineffectiveness and resistance development. Over the years, the Wuest and Minbiole groups have developed a wide array of QACs and QPCs with diverse structures to address this gap. In my dissertation, I first explored how an intrinsic physicochemical property of QACs can be correlated with their effectiveness as bactericidal agents to improve screening of numerous for disinfectants. Then, we investigated why cationic biocides with distinct chemical structures showed dramatic differences in effectiveness against P. aeruginosa, an important pathogen that displays high levels of intrinsic resistance to disinfectants. These investigations led us to uncover how these chemical differences can dictate the cellular target of these compounds in gram-negative pathogens, ultimately leading to differences cellular responses and genetic adaptations. Finally, we show that these strains not only have defined resistant determinants associated with adaptations to these different cationic biocides, but also affect P. aeruginosa virulence factor production and pathogenesis differently.
In summary, these studies highlight how cationic biocides can influence virulence in pathogens and highlight the importance of evaluating the intended effects of antimicrobials without overlooking the unintended effects they might have in bacterial physiology and pathogenesis.
Table of Contents
CHAPTER I Introduction………………………………………………………1
CHAPTER II Exploring the correlation of dynamic surface tension with antimicrobial activities of quaternary ammonium-based disinfectants……………………………………………………...20
CHAPTER III Highly effective biocides against Pseudomonas aeruginosa reveal new mechanistic insights across gram-negative bacteria…………………………………………………………...64
CHAPTER IV Adaptations to cationic biocide exposure differentially influences virulence factors and pathogenicity in Pseudomonas aeruginosa………………………………………………………106
CHAPTER V Discussion………………………………………………………141
Chapter VI Bibliography……………………………………………………152
APPENDIX Published Articles………………………………………...…….190
About this Dissertation
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