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

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...

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Autores principales: Ma, Kevin C., Mortimer, Tatum D., Hicks, Allison L., Wheeler, Nicole E., Sánchez-Busó, Leonor, Golparian, Daniel, Taiaroa, George, Rubin, Daniel H. F., Wang, Yi, Williamson, Deborah A., Unemo, Magnus, Harris, Simon R., Grad, Yonatan H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431566/
https://www.ncbi.nlm.nih.gov/pubmed/32807804
http://dx.doi.org/10.1038/s41467-020-17980-1
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author Ma, Kevin C.
Mortimer, Tatum D.
Hicks, Allison L.
Wheeler, Nicole E.
Sánchez-Busó, Leonor
Golparian, Daniel
Taiaroa, George
Rubin, Daniel H. F.
Wang, Yi
Williamson, Deborah A.
Unemo, Magnus
Harris, Simon R.
Grad, Yonatan H.
author_facet Ma, Kevin C.
Mortimer, Tatum D.
Hicks, Allison L.
Wheeler, Nicole E.
Sánchez-Busó, Leonor
Golparian, Daniel
Taiaroa, George
Rubin, Daniel H. F.
Wang, Yi
Williamson, Deborah A.
Unemo, Magnus
Harris, Simon R.
Grad, Yonatan H.
author_sort Ma, Kevin C.
collection PubMed
description 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.
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spelling pubmed-74315662020-08-28 Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae Ma, Kevin C. Mortimer, Tatum D. Hicks, Allison L. Wheeler, Nicole E. Sánchez-Busó, Leonor Golparian, Daniel Taiaroa, George Rubin, Daniel H. F. Wang, Yi Williamson, Deborah A. Unemo, Magnus Harris, Simon R. Grad, Yonatan H. Nat Commun Article 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. Nature Publishing Group UK 2020-08-17 /pmc/articles/PMC7431566/ /pubmed/32807804 http://dx.doi.org/10.1038/s41467-020-17980-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ma, Kevin C.
Mortimer, Tatum D.
Hicks, Allison L.
Wheeler, Nicole E.
Sánchez-Busó, Leonor
Golparian, Daniel
Taiaroa, George
Rubin, Daniel H. F.
Wang, Yi
Williamson, Deborah A.
Unemo, Magnus
Harris, Simon R.
Grad, Yonatan H.
Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae
title Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae
title_full Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae
title_fullStr Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae
title_full_unstemmed Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae
title_short Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae
title_sort adaptation to the cervical environment is associated with increased antibiotic susceptibility in neisseria gonorrhoeae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431566/
https://www.ncbi.nlm.nih.gov/pubmed/32807804
http://dx.doi.org/10.1038/s41467-020-17980-1
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