Nutrition University of California, Davis Davis, California, United States
Disclosure(s):
Weizhang Wen: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Emerging evidence suggests metal overexposure triggers the co-selection for metal and antibiotic resistance in bacteria. This study aims to investigate the impact of transition metal exposure on the efficacy of medically important antibiotics using in vitro bacterial culture of F18-positive Enterotoxigenic Escherichia coli (ETEC).
Methods: The antibiotic resistance of ETEC was evaluated under concurrent antibiotic and metal exposure or sequential exposure to metal and antibiotic exposure. The phenotypic response of ETEC to antibiotics and metals was assessed through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assay. The molecular and cellular mechanisms underlying altered phenotypic responses will be investigated using real-time quantitative PCR (qPCR), transcriptome sequencing, and metabolic assays will be employed to investigate the molecular and cellular mechanisms underlying the altered phenotypic responses.
Results: The MIC values of 5 antibiotics – Erythromycin, gentamicin, chloramphenicol, penicillin, and tetracycline – were assessed. Under concurrent antibiotic and metal exposure, ETEC showed increased resistance to erythromycin with the increase of copper sulfate, and to gentamicin with the increase of ferrous iron. Tetracycline MIC increased with ferrous and ferric iron exposure. Similarly, exposure to zinc sulfate and zinc oxide increased penicillin MIC. The MBC assay mirrored MIC results for each antibiotic, indicating metal exposure alters ETEC’s antibiotic resistance. Underlying mechanisms will be explored further through transcriptome, qPCR and metabolic assays.
Conclusions: Preliminary results suggest that metal overexposure increases bacterial resistance to antibiotics, warranting caution regarding metal element use in agriculture, especially livestock production. This research may enhance our understanding of the antibiotic resistance mechanism.
Funding Sources: Novo Nordisk Foundation and CLEAR center UC Davis
