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

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 Glade, both of which were inferred to have originated in East Asia. The dispersal of the major Glade from Asia happened in two separate waves expanding from similar to 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.

Automated summary

A study on Neisseria gonorrhoeae multilocus sequence type (ST) 1901 found that this lineage is commonly associated with treatment failure, particularly due to alleles linked to reduced susceptibility to extended-spectrum cephalosporins (ESCs). The genetic diversity of ST-1901 was classified into minor and major clades, both originating in East Asia and dispersing globally in waves, with one clade acquiring a gene that significantly reduces susceptibility to ESCs. Despite declining effective population sizes, the lineage has become a reservoir for clones resistant to ceftriaxone, a key drug for gonorrhea treatment.