Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand

Abstract

BackgroundAntimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health. No studies to date have examined the genomic epidemiology of gonorrhoea in the Western Pacific Region, where the incidence of gonorrhoea is particularly high.MethodsA population-level study of N. gonorrhoeae in New Zealand (October 2014 to May 2015). Comprehensive susceptibility testing and WGS data were obtained for 398 isolates. Relatedness was inferred using phylogenetic trees, and pairwise core SNPs. Mutations and genes known to be associated with resistance were identified, and correlated with phenotype.ResultsEleven clusters were identified. In six of these clusters, >25% of isolates were from females, while in eight of them, >15% of isolates were from females. Drug resistance was common; 98%, 32% and 68% of isolates were non-susceptible to penicillin, ciprofloxacin and tetracycline, respectively. Elevated MICs to extended-spectrum cephalosporins (ESCs) were observed in 3.5% of isolates (cefixime MICs ≥ 0.12 mg/L, ceftriaxone MICs ≥ 0.06 mg/L). Only nine isolates had penA XXXIV genotypes, three of which had decreased susceptibility to ESCs (MIC = 0.12 mg/L). Azithromycin non-susceptibility was identified in 43 isolates (10.8%); two of these isolates had 23S mutations (C2611T, 4/4 alleles), while all had mutations in mtrR or its promoter.ConclusionsThe high proportion of females in clusters suggests transmission is not exclusively among MSM in New Zealand; re-assessment of risk factors for transmission may be warranted in this context. As elevated MICs of ESCs and/or azithromycin were found in closely related strains, targeted public health interventions to halt transmission are urgently needed.

Host adaptation and convergent evolution increases antibiotic resistance without loss of virulence in a major human pathogen

“…Raw sequence reads are available on NCBI under Bioproject accession number PRJNA430457. Reads were quality-checked, trimmed and assembled using the Nullarbor pipeline v.1.20 (available at: https://github.com/tseemann/nullarbor), as previously described [60], but with the exception of the assembly step which was performed using Shovill (available at: https://github.com/tseemann/shovill), a genome assembler pipeline wrapped around SPAdes v.3.9.0 [61] which includes post-assembly correction. Assemblies were also reordered against reference strain K. pneumoniae 30660/NJST258_1 (accession number CP006923) using progressive Mauve v.2.4.0 [62] prior to annotation with Prokka [63] and screened for antibiotic resistance genes using Abricate v.0.6 (available at: https://github.com/tseemann/abricate).…”

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

“…In the United States, lineages with reduced susceptibility to cefixime were found to be primarily circulating among MSM, and transmission from MSM to men who have sex with women (MSW) occurred more often than MSW to MSM transmission . WGS of N. gonorrhoeae populations in New Zealand shows that the majority of clusters contain isolates from both men and women, suggesting the absence of clones associated with exclusively MSM transmission . While the N. gonorrhoeae global population does not show geographic structure, examining WGS of isolates from smaller scales (i.e., London) shows that transmission links are associated with shorter geographic distances .…”

“…Population structure analyses based on Bayesian methods have identified 5-12 clusters in N. gonorrhoeae populations, depending on the data set, and these clusters and major clades defined by phylogenetic analysis have little to no geographic structure. [21][22][23][24] In N. meningitidis, clade-specific restriction modification systems, competition between lineages, and selection by the immune system contribute to the population structure, 25,26 but the factors that maintain population structure in N. gonorrhoeae have not been identified. The global distribution of these major groups suggests that international transmission of N. gonorrhoeae is relatively common.…”

“…50 WGS of N. gonorrhoeae populations in New Zealand shows that the majority of clusters contain isolates from both men and women, suggesting the absence of clones associated with exclusively MSM transmission. 23 While the N. gonorrhoeae global population does not show geographic structure, examining WGS of isolates from smaller scales (i.e., London) shows that transmission links are associated with shorter geographic distances. 24 Beyond inferring likely transmission links, phylogenetic analyses utilizing a molecular clock enable additional inferences.…”

Lowering the Barriers to Routine Whole-Genome Sequencing of Bacteria in the Clinical Microbiology Laboratory

“…Correlating the phenotypic susceptibility and resistance of a bacterial isolate to a WGS genotype also needs to be performed on an organism-by-organism basis. Recent studies have empirically demonstrated that predicting susceptibility and resistance using WGS data is feasible or potentially feasible for S. aureus (13)(14)(15), Enterobacteriaceae (22)(23)(24)(25), Pseudomonas aeruginosa (26,27), Campylobacter (28), Helicobacter pylori (29), Neisseria gonorrhoeae (30,31), and Mycobacterium tuberculosis (13,18,(32)(33)(34)(35). In one of these studies, WGS data from more than 1,700 isolates of Salmonella enterica were used to predict susceptibility and resistance to 13 antimicrobial agents (22).…”