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bioRxiv · 10.1101/2024.12.12.628210

Collateral sensitivity and cross resistance in six species of bacteria exposed to six classes of antibiotics

Wang, X. H.·Nong, L.·Schaar, G.·Jonker, M. J.·de Leeuw, W.·Ter Kuile, B. H.
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Abstract

De novo resistance can be developed in bacteria because of exposure to sublethal concentrations of antibiotics. Once the strain has become resistant to an initial antibiotic, this can cause cross-resistance or collateral sensitivity to a second antimicrobial. Specific collateral sensitivity is rarely conserved across species because the mechanisms triggered in different microorganisms to resist antibiotics are often different. In this study, we explored which collateral sensitivity or cross resistance networks are present in six species of bacteria with induced de novo-resistance. These six species were induced to become resistant to amoxicillin/cefepime, enrofloxacin, kanamycin, tetracycline, erythromycin and chloramphenicol(1). After that, the collateral sensitivity and the cross-resistance networks were evaluated by measuring increase or decrease of MIC of thirteen antibiotics that are often used in the clinic. Collateral sensitivity for kanamycin occurred in five species of strains resistant to chloramphenicol and tetracycline and for {beta}-lactam in strains of five species resistant to kanamycin. Further genetic analysis clarified that fusA consistently mutated in five species of bacteria made de novo resistant against kanamycin, suggesting that fusA operates in parallel with the other mechanisms related to antimicrobial resistance Based on considerations of resistance, a treatment protocol starting with chloramphenicol/tetracycline, followed by kanamycin and ending with amoxicillin may eliminate bacteria that have developed resistance against the initial treatment.

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Wang, X. H., Nong, L., Schaar, G., Jonker, M. J., de Leeuw, W., Ter Kuile, B. H.. 2024-12-13. Collateral sensitivity and cross resistance in six species of bacteria exposed to six classes of antibiotics. https://doi.org/10.1101/2024.12.12.628210

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