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Investigation of the effects of ampicillin and ceftazidime on Proteus mirabilis using metabolomic approaches and bioinformatics analyses

Folia Microbiol (Praha). 2026 Jul 31. doi: 10.1007/s12223-026-01567-2. Online ahead of print.

ABSTRACT

Antibiotic resistance is the ability of microorganisms to survive and proliferate despite exposure to antibiotics that would normally inhibit or kill susceptible strains. This resistance can make antibiotics ineffective or diminish their ability to combat microorganisms, complicating the treatment of infections and potentially leading to serious complications. To combat antibiotic resistance, a comprehensive analysis of changes in the metabolic activities of microorganisms is crucial for understanding the underlying mechanisms. Proteus mirabilis is a critical pathogen, particularly as a common cause of urinary tract infections (UTIs), especially in women. Typically, treating P. mirabilis infections relies on antibiotic-based therapies. However, when faced with resistant strains, treatment options become limited. This research aims to simulate how antibiotic resistance develops in P. mirabilis when exposed to sub-inhibitory concentrations of ampicillin and to explore whether ampicillin-resistant strains display cross-resistance to other antibiotics through metabolomic approaches. For this purpose, P. mirabilis strains were gradually exposed to sub-inhibitory concentrations of ampicillin using the disk diffusion method, leading to the selection of resistant passages. Ampicillin and ceftazidime were then applied to both ampicillin-resistant passages and sensitive control strains, and differences in their metabolomic profiles were compared. The metabolomic data obtained from this study were supported by statistical and bioinformatics analyses to facilitate metabolic pathway mapping, comprehend metabolic alterations, and identify interactions among metabolites. Metabolomic studies in antibiotic resistance research provide valuable insights into identifying metabolic alterations in resistant microorganisms, understanding microbial responses to antibiotic exposure, clarifying the effects of antibiotics on metabolic pathways, and gaining a comprehensive perspective on the mechanisms of antibiotic resistance.

PMID:42536331 | DOI:10.1007/s12223-026-01567-2

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