Effects of small molecules produced by commensal bacteria on antibiotic resistant Pseudomonas aeruginosa.

Date
2022-04
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Abstract

In recent years the emergence and spread of antibiotic-resistant bacterial strains has become a global health threat, prompting the World Health Organization to publish a global priority list for new antibiotic development, including the pathogen Pseudomonas aeruginosa. One strategy to combat antimicrobial resistance is to identify naturally occurring small molecules, called antibiotic adjuvants, which increase the efficacy of antibiotics. This thesis investigated whether metabolites produced by commensal bacteria, identified through in vitro screening, can increase susceptibility of antibiotic-resistant P. aeruginosa to existing antibiotics. Staphylococcus lugdunensis was identified in vitro as a producer of the metabolite oleamide that reduces growth of antibiotic-resistant P. aeruginosa in combination with antibiotics. We hypothesized that S. lugdunensis production of oleamide will increase sensitivity of P. aeruginosa to antibiotic treatment in vivo. Gnotobiotic animals were utilized to determine colonization dynamics between adjuvant producing bacterial isolates, S. lugdunensis, Flavonifractor plautii and Bacteroides uniformis, and the human pathogen P. aeruginosa. Colonization with S. lugdunensis and P. aeruginosa resulted in the displacement of P. aeruginosa over time. However, stable colonization with P. aeruginosa and F. plautii or B. uniformis was observed, and the addition of S. lugdunensis to these bi-colonized mice did not cause a loss of P. aeruginosa. Antibiotic treatment in mice colonized with S. lugdunensis, F. plautii, B. uniformis and P. aeruginosa did not result in an increased susceptibility to antibiotics by P. aeruginosa. Administration of purified oleamide in combination with antibiotics via oral gavage did not increase susceptibility of P. aeruginosa to antibiotics. Taking these results together, we can conclude S. lugdunensis influences P. aeruginosa colonization in vivo, although antibiotic susceptibility was not influenced by the presence of antibiotic adjuvant producing bacterial species or the administration of purified oleamide.

Description
Keywords
Microbiome, Microbiology, Antibiotic resistance, Antibiotic adjuvant
Citation
Pyke, S. (2022). Effects of small molecules produced by commensal bacteria on antibiotic resistant Pseudomonas aeruginosa. (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.