Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance

Abstract

SummaryObjectivesAntimicrobial resistance (AMR) threatens our ability to treat the sexually transmitted bacterial infection gonorrhoea. The increasing availability of whole genome sequence (WGS) data from Neisseria gonorrhoeae isolates, however, provides us with an opportunity in which WGS can be mined for AMR determinants.MethodsChromosomal and plasmid genes implicated in AMR were catalogued on the PubMLST Neisseria database (http://pubmlst.org/neisseria). AMR genotypes were identified in WGS from 289 gonococci for which MICs against several antimicrobial compounds had been determined. Whole genome comparisons were undertaken using whole genome MLST (wgMLST).ResultsClusters of isolates with distinct AMR genotypes were apparent following wgMLST analysis consistent with the occurrence of genome wide genetic variation. This included the presence of the gonococcal genetic island (GGI), a type 4 secretion system shown to increase recombination and for which possession was significantly associated with AMR to multiple antimicrobials.ConclusionsEvolution of the gonococcal genome occurs in response to antimicrobial selective pressure resulting in the formation of distinct N. gonorrhoeae populations evidenced by the wgMLST clusters seen here. Genomic islands offer selective advantages to host bacteria and possession of the GGI may, not only facilitate the spread of AMR in gonococcal populations, but may also confer fitness advantages.

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

“…Similar T4SSs can be found in other proteobacteria; however, flanking regions are not conserved . DNA secretion may facilitate horizontal gene transfer, including resistance acquisition, and biofilm formation . The T4SS can also enable intracellular survival of N. gonorrhoeae via iron acquisition by an unknown mechanism, which is independent of DNA secretion .…”

“…39 DNA secretion may facilitate horizontal gene transfer, including resistance acquisition, and biofilm formation. 36,37,40 The T4SS can also enable intracellular survival of N. gonorrhoeae via iron acquisition by an unknown mechanism, which is independent of DNA secretion. 41 These mobile elements are found in diverse N. gonorrhoeae strains and are not confined to a particular clade.…”

Secretion of Chromosomal DNA by the Neisseria gonorrhoeae Type IV Secretion System

“…The mechanism of T4SS-mediated gene transfer may result in some regions of the chromosome being transferred more than others or GGI + strains more effectively spreading their genes to other strains or species. The identification of antibiotic resistance associated with the genomic presence of the GGI suggests that the T4SS does have measureable effects on gonococcal populations (Harrison et al 2016). Experiments to identify the mechanisms underlying the increased likelihood of GGI + strains to exhibit antimicrobial resistance may give the most insight into the medically relevant role of the T4SS in N. gonorrhoeae infection.…”

“…In a 2016 study, a significant positive correlation between the presence of the GGI and resistance to a variety of common antimicrobials was found (Harrison et al 2016). Investigators mined whole genome sequencing data for antimicrobial resistance (AMR) determinants from 289 gonococcal isolates from which MIC (minimal inhibitory concentration) values against several antimicrobials were available.…”

“…74% of the GGI + strains were predicted to be resistant to Ciprofloxacin compared to 33% of the GGI − strains. The mechanisms governing this association are unknown, however possibilities include increased horizontal gene transfer due to the presence of the T4SS, activity of the putative YdbB-YdcA toxin-antitoxin system, or competition somewhere during the evolutionary history of N. gonorrhoeae between plasmids and the GGI prior to its chromosomal insertion that could have altered resistance phenotypes (Harrison et al 2016). …”