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Anaerobic conditions unmask antimicrobial resistance

A. Creasy-Marrazzo, M.M. Saber, M. Kamat, L. S. Bailey, F. Qadri, K. B. Basso, View ORCID ProfileB. J. Shapiro, View ORCID ProfileE. J. Nelson
doi: https://doi.org/10.1101/2021.06.26.450051
A. Creasy-Marrazzo
1Departments of Pediatrics and Environmental and Global Health, University of Florida, Gainesville, FL, USA
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M.M. Saber
2Department of Microbiology & Immunology, McGill University
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M. Kamat
3Departments of Chemistry, University of Florida, Gainesville, FL, USA
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L. S. Bailey
3Departments of Chemistry, University of Florida, Gainesville, FL, USA
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F. Qadri
4Infectious Diseases Division (IDD) & Nutrition and Clinical Services Division (NCSD), International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh
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K. B. Basso
3Departments of Chemistry, University of Florida, Gainesville, FL, USA
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B. J. Shapiro
2Department of Microbiology & Immunology, McGill University
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  • ORCID record for B. J. Shapiro
E. J. Nelson
1Departments of Pediatrics and Environmental and Global Health, University of Florida, Gainesville, FL, USA
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  • For correspondence: eric.nelson@ufl.edu
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Abstract

Antimicrobial resistance (AMR) in Gram negative enteropathogens is an urgent threat to the antibiotic formulary. These taxa undergo anaerobic respiration within the host, yet little is known about how anaerobic conditions influence antimicrobial resistance (AMR). The facultative enteropathogen Vibrio cholerae was chosen as a model to determine the impact of anaerobic growth on AMR because cholera is one of the few non-invasive diarrhoeal diseases for which antibiotics are indicated, albeit conditionally. V. cholerae isolates from a single outbreak were tested for resistance by minimal inhibitory concentrations (MIC) under aerobic and anaerobic conditions against clinically relevant antibiotics. Here we show that the odds of classifying isolates as resistant under anaerobic compared to aerobic conditions increased over 20 times for ciprofloxacin and 50 times for azithromycin, yet for doxycycline, all isolates remained below the breakpoint for resistance. Genome-wide association studies (GWAS) found significant associations between known and unknown genetic elements and AMR phenotypes that varied by oxygen exposure and antibiotic concentrations. In most cases, AMR phenotypes were more heritable – and more genes significantly associated with AMR were discovered – under anaerobic conditions compared to aerobic conditions. These findings challenge the paradigm of testing facultative enteropathogens for AMR under aerobic conditions alone. This experimental approach establishes a new, more sensitive framework to track and investigate mechanisms of AMR.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 27, 2021.
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Anaerobic conditions unmask antimicrobial resistance
A. Creasy-Marrazzo, M.M. Saber, M. Kamat, L. S. Bailey, F. Qadri, K. B. Basso, B. J. Shapiro, E. J. Nelson
bioRxiv 2021.06.26.450051; doi: https://doi.org/10.1101/2021.06.26.450051
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Anaerobic conditions unmask antimicrobial resistance
A. Creasy-Marrazzo, M.M. Saber, M. Kamat, L. S. Bailey, F. Qadri, K. B. Basso, B. J. Shapiro, E. J. Nelson
bioRxiv 2021.06.26.450051; doi: https://doi.org/10.1101/2021.06.26.450051

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