Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae

Kevin C. Ma, Tatum D. Mortimer, Allison L. Hicks, Nicole E. Wheeler, Leonor Sánchez-Busó, Daniel Golparian, George Taiaroa, Daniel H. F. Rubin, Yi Wang, Deborah A. Williamson, Magnus Unemo, Simon R. Harris and Yonatan H. Grad ()
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Kevin C. Ma: Harvard T.H. Chan School of Public Health
Tatum D. Mortimer: Harvard T.H. Chan School of Public Health
Allison L. Hicks: Harvard T.H. Chan School of Public Health
Nicole E. Wheeler: Wellcome Genome Campus
Leonor Sánchez-Busó: Wellcome Genome Campus
Daniel Golparian: Örebro University
George Taiaroa: The University of Melbourne at The Peter Doherty Institute for Infection and Immunity
Daniel H. F. Rubin: Harvard T.H. Chan School of Public Health
Yi Wang: Harvard T.H. Chan School of Public Health
Deborah A. Williamson: The University of Melbourne at The Peter Doherty Institute for Infection and Immunity
Magnus Unemo: Örebro University
Simon R. Harris: Wellcome Genome Campus
Yonatan H. Grad: Harvard T.H. Chan School of Public Health

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Neisseria gonorrhoeae is an urgent public health threat due to rapidly increasing incidence and antibiotic resistance. In contrast with the trend of increasing resistance, clinical isolates that have reverted to susceptibility regularly appear, prompting questions about which pressures compete with antibiotics to shape gonococcal evolution. Here, we used genome-wide association to identify loss-of-function (LOF) mutations in the efflux pump mtrCDE operon as a mechanism of increased antibiotic susceptibility and demonstrate that these mutations are overrepresented in cervical relative to urethral isolates. This enrichment holds true for LOF mutations in another efflux pump, farAB, and in urogenitally-adapted versus typical N. meningitidis, providing evidence for a model in which expression of these pumps in the female urogenital tract incurs a fitness cost for pathogenic Neisseria. Overall, our findings highlight the impact of integrating microbial population genomics with host metadata and demonstrate how host environmental pressures can lead to increased antibiotic susceptibility.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17980-1

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DOI: 10.1038/s41467-020-17980-1

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