Antibiotic Treatment Regimes as a Driver of the Global Population Dynamics of a Major Gonorrhea Lineage

Author:

Osnes Magnus N12,Dorp Lucy van3,Brynildsrud Ola B1,Alfsnes Kristian1,Schneiders Thamarai4,Templeton Kate E5,Yahara Koji6,Balloux Francois3ORCID,Caugant Dominique A1,Eldholm Vegard1ORCID

Affiliation:

1. Division of Infectious Disease Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway

2. Department of Biostatistics, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway

3. UCL Genetics Institute, University College London, London, United Kingdom

4. Division of Infection Medicine, University of Edinburgh, Edinburgh, United Kingdom

5. Department of Laboratory Medicine, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, United Kingdom

6. Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan

Abstract

Abstract The Neisseria gonorrhoeae multilocus sequence type (ST) 1901 is among the lineages most commonly associated with treatment failure. Here, we analyze a global collection of ST-1901 genomes to shed light on the emergence and spread of alleles associated with reduced susceptibility to extended-spectrum cephalosporins (ESCs). The genetic diversity of ST-1901 falls into a minor and a major clade, both of which were inferred to have originated in East Asia. The dispersal of the major clade from Asia happened in two separate waves expanding from ∼1987 and 1996, respectively. Both waves first reached North America, and from there spread to Europe and Oceania, with multiple secondary reintroductions to Asia. The ancestor of the second wave acquired the penA 34.001 allele, which significantly reduces susceptibility to ESCs. Our results suggest that the acquisition of this allele granted the second wave a fitness advantage at a time when ESCs became the key drug class used to treat gonorrhea. Following its establishment globally, the lineage has served as a reservoir for the repeated emergence of clones fully resistant to the ESC ceftriaxone, an essential drug for effective treatment of gonorrhea. We infer that the effective population sizes of both clades went into decline as treatment schemes shifted from fluoroquinolones via ESC monotherapy to dual therapy with ceftriaxone and azithromycin in Europe and the United States. Despite the inferred recent population size decline, the short evolutionary path from the penA 34.001 allele to alleles providing full ceftriaxone resistance is a cause of concern.

Funder

The National Graduate School in Infection Biology and Antimicrobials

Newton Fund UK-China NSFC initiative

BBSRC

Publisher

Oxford University Press (OUP)

Subject

Genetics,Molecular Biology,Ecology, Evolution, Behavior and Systematics

Reference51 articles.

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4. 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults;Bignell;Int J STD AIDS,2013

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