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


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.

SUBMITTER: Ma KC 

PROVIDER: S-EPMC7431566 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Ma Kevin C KC   Mortimer Tatum D TD   Hicks Allison L AL   Wheeler Nicole E NE   Sánchez-Busó Leonor L   Golparian Daniel D   Taiaroa George G   Rubin Daniel H F DHF   Wang Yi Y   Williamson Deborah A DA   Unemo Magnus M   Harris Simon R SR   Grad Yonatan H YH  

Nature communications 20200817 1


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 su  ...[more]

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