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

KC Ma; TD Mortimer; AL Hicks; NE Wheeler; L Sánchez-Busó; D Golparian; G Taiaroa; DHF Rubin; Y Wang; DA Williamson; M Unemo; SR Harris; YH Grad

Journal article

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

KC Ma, TD Mortimer, AL Hicks, NE Wheeler, L Sánchez-Busó, D Golparian, G Taiaroa, DHF Rubin, Y Wang, DA Williamson, M Unemo, SR Harris, YH Grad

Nature Communications | NATURE PORTFOLIO | Published : 2020

DOI: 10.1038/s41467-020-17980-1

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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 urog..

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University of Melbourne Researchers

George Taiaroa Author

Deborah Williamson Author

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UNDERSTANDING, REDUCING AND PREVENTING COMMUNICABLE DISEASES USING APPLIED PATHOGEN GENOMICS

Infectious diseases are a major threat to human health. New molecular methods, particularly whole genome sequencing, promise a revolution in..

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Awarded by Meningitis Research Foundation

Funding Acknowledgements

This work was supported by the NIH/NIAID grant 1R01AI132606-01 and the Smith Family Foundation. T.D.M. is additionally supported by the NIH/NIAID F32AI145157, and K.C.M. is additionally supported by the NSF GRFP. D.H.F.R. was supported by award Number T32GM007753 from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. D.A.W. is supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia (GNT1123854). Portions of this research were conducted on the O2 high-performance computing cluster, supported by the Research Computing Group at Harvard Medical School. This publication made use of the Meningitis Research Foundation Meningococcus Genome Library (http://www.meningitis.org/research/genome) developed by Public Health England, the Wellcome Trust Sanger Institute, and the University of Oxford as a collaboration and funded by the Meningitis Research Foundation. The authors additionally thank Crista Wadsworth, Samantha Palace, and other members of the Grad Lab for helpful comments during development of the project.