Genomic Analysis Reveals Antibiotic-Susceptible Clones and Emerging Resistance in Neisseria gonorrhoeae in Saskatchewan, Canada

Abstract

Whole genome sequencing was used to identify mutations in antibiotic resistance-conferring genes, to compare susceptibility predictions with minimum inhibitory concentrations and to ascertain strain types in 99 isolates of Neisseria gonorrhoeae. Genotypes associated with susceptibility as well as MIC creep or emerging resistance were noted. Phylogenomic analysis revealed three distinctive clades and putative gonococcal transmission linkages involving a tetracycline resistant N. gonorrhoeae outbreak and the clonal spread of susceptible isolates in men.

Focused Commentary; About Revision of CLSI Antimicrobial Breakpoints, 2018-2021

“…Even at an MIC ≤ 1 μg/mL, mtr (multiple transferable resistance) efflux pump gene mutations are occasionally found (20).…”

“…Here, we suggest deleting the S breakpoint in N. gonorrheae, such as with daptomycin. Instead, we recommend the introduction of the SDD concept because the therapeutic effect was observed at a 2 g azithromycin dose and treatment failures were occasionally found with MICs greater than 0.5 μg/mL (19,20). In particular, because we do not know the therapeutic effect in the MIC range of 2-16 μg/mL, and clonal spreads with strains with mtr gene mutations are occasionally found, we should determine the intermediate and resistant breakpoints among isolates with MICs of 2-16 μg/mL.…”

Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests

“…Machine learning models that predict resistance phenotype from genotype rely on datasets that provide both. Regional gonococcal surveillance programs (such as GISP, Euro GASP, WHO‐GASP, and ASGAP) and smaller epidemiological studies have reported genome sequences and AMR profiles from over 18,000 clinical isolates of N. gonorrhoeae ; 16,17,23,49,52–55,57–70,101,102 many of these have been curated and aggregated in databases, such as Pathogenwatch 66 . But the sampling strategies differ among surveillance programs, as can the quality of the sequencing or phenotypic data.…”

“…Much work has been done to determine the genetic modulators of AMR in N. gonorrhoeae , 34–48 with a focus on the antibiotics for which antimicrobial susceptibility test (AST) phenotypes are available—thus, most data are for antibiotics in recent use (ceftriaxone, cefixime, azithromycin, and ciprofloxacin) as well as others for which surveillance programs often collect data (penicillin and tetracycline) 16,17,23,25,49–72 . Most of the loci that account for a large extent of resistance in circulating populations in areas of high surveillance have been well characterized, 66,73 with several recent additions to the list of genetic modulators being described, 18,74–77 including some of increasing prevalence, such as the mosaic mtr 78,79 (where mosaicism refers to interspecies recombination between N. gonorrhoeae and another Neisseria species).…”