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Raphaël Charron – 25/11/2024

PhD Defense:

Impact of bacterial biofilm adaptation to biocides on antibiotic resistance

The increase in antimicrobial resistance increase poses a significant threat to public health. Identifying factors contributing to the emergence of antibiotic resistance in industrial environments is crucial for adapting our practices and limiting the emergence of antimicrobial resistance. Biocidal substances used for disinfection procedures could contribute to the selection of cross-resistance to antibiotics in bacterial populations. However, very few data are available on biofilms, which are surface-associated bacterial communities that represent the primary bacterial lifestyle and exhibit specific adaptation capacities. Therefore, this thesis aimed to better understand how the biofilm lifestyle affects bacterial adaptation to biocidal stresses and the cross-selection of antibiotic resistance. Biofilms of nine Escherichia coli strains were exposed to four biocidal active substances for a month, and resistance to various antibiotics was quantified. Phenotypic and genomic characterizations of resistant variants provided insights into the role of biofilms in the selection of these resistances and the underlying mechanisms. Links between the exposure to several biocides and antibiotic cross-resistances were identified. Exposure to N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine (Triamine, TMN) and benzalkonium chloride (BAC) led to a significant increase in rifampicin-resistant (RifR) variants in biofilms compared with exposure to H2O. A recurrence of LPS modifications was identified in the RifR variants from the TMN condition. These variants had competitive advantages over parental strains at both the individual and collective biofilm levels, supporting the likelihood of a higher risk of dissemination throughout the food chain. Another association was found between the exposure to polyhexamethylene biguanide (PHMB) and the selection of resistance to aminoglycosides. Results revealed that PHMB induced structural modulations in biofilms that altered the physiological response in various strains, which was associated with the emergence of an adaptive cross-resistance to gentamicin. Overall, this research highlights the importance of studying biofilms, which shape the evolutionary pathways of bacteria. Findings will be used to better assess the risks associated with biocide usage in relation to antibiotic resistance, and ultimately identify cross-resistance development markers that can be used to develop surveillance tools in the food chain.

 

 The defense will be held in Rennes the 25th of November 2024 at 2pm. For those who wish to attend, a Zoom link is available on request (raphael.charron@anses.fr)

 

Supervised by

Arnaud Bridier (arnaud.bridier@anses.fr) and Romain Briandet (romain.briandet@inrae.fr)

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