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Table 2 List of N. gonorrhoeae genetic antimicrobial resistance (AMR) determinants in Pathogenwatch. References that report evidence of association of each mechanism with AMR in clinical isolates and/or where their role on AMR has been confirmed in the laboratory through, e.g. transformation experiments, are included in the table. Effect: R = resistance, I = susceptibility but increased exposure, A = additive effect, N = negative effect. R and I follow the EUCAST clinical breakpoints except for azithromycin, for which the epidemiological cut-off (ECOFF) is reported and used instead

From: A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch

Antibiotic (MIC breakpoint mg/L) Genetic AMR determinants Effect Evidence (references)
Azithromycin
(R: MIC>1, ECOFF)
23S rDNA 2045A>G substitution (2059A>G in E. coli) R [75]
23S rDNA 2597C>T substitution (2611C>T in E. coli) R [88]
ermA, ermB, ermC, ermF genes R [89, 90]
ereA, ereB genes R [22]
mefA gene R [90, 91]
macAB promoter -48G>T substitutiona R [92]
mtrR promoter mosaicb
N. meningitidis-like mosaic (n = 1) R [23]
N. lactamica-like mosaic (n = 2) R [23]
mtrD mosaicb
N. meningitidis-like mosaic (n = 1) R [23]
N. lactamica-like mosaic (n = 2) R [23]
mtrR promoter -57delAa A [93, 94]
mtrR G45D A [95, 96]
mtrC loss-of-function N [26]
rplV ARAK tandem duplication (position 90) R [18]
rplV KGPSLK tandem duplication (position 83) R [18]
rplD G70D A [25]
Ceftriaxonec
(R: MIC>0.125)
penA mosaic (A311V, I312M, V316P/T, T483S and G545S) R [97, 98, 100]
penA V316P, T483S, A501P/V, G542S R [97, 100]
rpoB P157L, G158V, R201H R [21]
rpoD D92–95 deletion, E98K I [21]
Cefiximec
(R: MIC>0.125)
mtrR G45D A [95, 96]
penA mosaic (I312M, V316T, G545S) R [97, 98, 100]
penA mosaic (A311V, I312M, V316P/T, T483S and G545S) R [97, 98, 100]
penA V316P, T483S, A501P I [97, 100]
rpoB P157L, G158V, R201H I [21]
rpoD D92-95 deletion, E98K I [21]
Ciprofloxacin
(I: 0.03<MIC≤0.06;
R: MIC>0.06)
gyrA S91F, D95A/N R [99]
gyrA D95G I [99]
norM promoter -7A>G, -104C>T substitutionsa I [101]
parC D86N, S87R R [99]
parC S87I/N, S88P, E91K I [99]
parE G410V I [102]
Tetracyclined
(I: 0.5<MIC≤1;
R: MIC>1)
mtrR A39T, G45D A [95, 96]
mtrR loss-of-function I [22]
mtrR promoter -56A>C substitution, -57delA deletiona I [23, 93, 94]
mtrR promoter -131G>A (mtrC -120G>A substitution, mtr120)a I [95]
rpsJ V57M I [103]
tetM gene R [104]
Penicillins
(I: 0.06<MIC≤1;
R: MIC>1)
blaTEM gene R [105]
mtrR G45D I [95, 96]
mtrR A39T A [95]
mtrR loss-of-function I [22]
mtrR promoter -56A>C, -57delAa I [23, 94]
mtrR promoter -131G>A (mtrC -120G>A substitution, mtr120)a I [95]
penA I312M, V316P/T, ins346D, T483S, A501P/T/V, G542S, G545S, P551S I [97, 100]
penA mosaic (I312M, V316T, G545S) A [97, 98, 100]
ponA1 L421P I [106]
porB1b G120K, A121N/D I [107]
Spectinomycin
(R: MIC>64)
16S rDNA 1184C>T (1192C>T in E. coli) R [108]
rpsE T24P R [109]
rpsE V27- deletion, K28E R/A [109]
Sulfonamidese folP R228S R [22, 110]
  1. aNomenclature of the mutations on the macAB, mtrR and norM promoter regions is based on N. gonorrhoeae coordinates considering the distance from the start of the macAB, mtrR and norM genes, respectively. bNote that mosaics are caused by recombination events, which can have variable breakpoints with different effects on azithromycin MIC if any. In this version, we have included the three mosaics described by Wadsworth et al. [23], but the list will be expanded as new mosaic mtr (intergenic region between mtrR and mtrC) and mtrD alleles having an effect on azithromycin MICs are published. cThe list of genetic AMR mechanisms for the ESCs ceftriaxone and cefixime does not include all known porB1b or mtrR-associated variants as their effect was found not to be relevant in increasing MIC on the benchmark analyses for phenotypic AMR prediction purposes despite the experimental evidence reported in Zhao et al. [111]. In the case of strains carrying penA-associated mutations, their immediate predicted phenotype is that of those carrying penA-associated variants. dThe list of genetic AMR mechanisms for tetracycline does not include porB1b mutations as their effect was found not to be relevant in increasing MIC on the benchmark analyses for phenotypic AMR prediction purposes. eSulfonamides are not a treatment alternative for gonorrhoea; however, the folP R228S mutation is kept in this version of the library for surveillance purposes