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Cell morphology as biomarker of carbapenem exposure

Abstract

Characterizing the physiological response of bacterial cells to antibiotics is crucial for designing diagnostic techniques, treatment choices, and drug development. While bacterial cells at sublethal doses of antibiotics are commonly characterized, the impact of exposure to high concentrations of antibiotics on bacteria after long-term serial exposure and their effect on withdrawal need attention for further characterization. This study investigated the effect of increasing imipenem concentrations on carbapenem-susceptible (S) and carbapenem-resistant (R) E. coli on their growth adaptation and cell surface structure. We exposed the bacterial population to increasing imipenem concentrations through 30 exposure cycles. Cell morphology was observed using a 3D laser scanning confocal microscope (LSCM) and transmission electron microscope (TEM). Results showed that the exposure resulted in significant morphological changes in E. coli (S) cells, while minor changes were seen in E. coli (R) cells. The rod-shaped E. coli (S) gradually transformed into round shapes. Further, the exposed E. coli (S) cells’ surface area-to-volume ratio (SA/V) was also significantly different from the control, which is non-exposed E. coli (S). Then, the exposed E. coli (S) cells were re-grown in antibiotic-free environment for 100 growth cycles to determine if the changes in cells were reversible. The results showed that their cell morphology remained round, showing that the cell morphology was not reversible. The morphological response of these cells to imipenem can assist in understanding the resistance mechanism in the context of diagnostics and antibacterial therapies.

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Acknowledgements

Research related to this article was supported by the Targeted Support Grant for Technology Development (TSGTD), Michigan State University Foundation; the USDA Hatch MICL 02782; USDA Hatch Multistate NC1194 MICL 04233 (RA101064) and the USDA-NIFA project 2022-67017-36982. Further, the Turkish Ministry of Education sponsored O. Caliskan‐Aydogan’s Ph.D. program at Michigan State University. Furthermore, we want to thank Dr. Alicia Withrow for assisting in taking TEM images and Dr. Shannon Manning and Dr. Saad A. Sharief for many helpful discussions and communication of the research results.

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Oznur Caliskan-Aydogan: Conceptualization, Methodology, Data curation, Investigation, Roles/Writing - original draft, and Writing - review & editing. Chloe Zaborney Kline: Investigation, Visualization, Methodology, Evangelyn C. Alocilja: Conceptualization, Methodology Resources, Funding acquisition, Project administration, Writing - review & editing, and Supervision.

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Correspondence to Evangelyn C. Alocilja.

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Caliskan-Aydogan, O., Zaborney Kline, C. & Alocilja, E.C. Cell morphology as biomarker of carbapenem exposure. J Antibiot (2024). https://doi.org/10.1038/s41429-024-00749-9

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