Osnes, MN;
Van Dorp, L;
Brynildsrud, OB;
Alfsnes, K;
Schneiders, T;
Templeton, KE;
Yahara, K;
... Eldholm, V; + view all
(2020)
Antibiotic Treatment Regimes as a Driver of the Global Population Dynamics of a Major Gonorrhea Lineage.
Molecular Biology and Evolution
, Article msaa282. 10.1093/molbev/msaa282.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Antibiotic Treatment Regimes as a Driver of the Global Population Dynamics of a Major Gonorrhea Lineage |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/molbev/msaa282 |
| Publisher version: | https://doi.org/10.1093/molbev/msaa282 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Neisseria gonorrhoeae, antibiotic resistance, evolution, phylogeography |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10119926 |
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