Fig 1.
Typing, genomic, and phenotypic antimicrobial resistance features of the 2 ATCC reference strains, 8 clinical strains, and the 3 WHO N. gonorrhoeae reference WHO X, WHO Y, and WHO Z strains.
Red indicates a resistant allele, while blue indicates a wild type allele. The MIC values are color-coded from dark blue (lower values) to red (higher values) for each drug. MIC values in bold indicate resistance based on EUCAST breakpoints. Clinical resistance breakpoints are not available for azithromycin, ertapenem, ceftazidime/avibactam, ceftolozane/tazobactam, and piperacillin/tazobactam. The sensitive breakpoint values according to EUCAST are: PEN ≤ 0.06, CFM ≤ 0.125, CTX ≤ 0.125, CRO ≤ 0.125, CIP ≤ 0.03, and TET ≤ 0.5. Azithromycin lacks clinical EUCAST breakpoints; therefore, EUCAST’s epidemiological cut-off (ECOFF) value of MIC > 1 mg/L was used to define resistance. a Please refer to Table 1 for antibiotic abbreviations.
Table 1.
Minimum inhibitory concentrations of β-lactam antibiotics and β-lactamase inhibitors in the studied N. gonorrhoeae strains.
Fig 2.
Heatmap representing the PBP IC50s of β-lactam antibiotics and β-lactamase inhibitors in the studied N. gonorrhoeae strains.
a PBP, penicillin-binding proteins. Mosaic alleles highlighted in grey. b a fixed concentration of the BLI avibactam or tazobactam was used (4 mg/L). The median values from 3 experiments are shown. Please see Table 1 for drug abbreviations. When the main PBP target was not inhibited using the regular concentrations (0.001 to 0.125 mg/L) an extended range (0.016 to 2 mg/L or 1 to 512 mg/L) was used.
Fig 3.
Scatter plots were employed to illustrate the correlation between PBP2 IC50 values and the minimum inhibitory concentrations (MIC) of β-lactam antibiotics, β-lactamase inhibitors (BLI), and the combination of β-lactams with BLI.
Each plot depicts the relationship between PBP2 IC50 and the MICs for each drug across all tested strains. The data were represented on a logarithmic scale and analyzed using a robust fitting method in GraphPad Prism. Light grey dots represent outliers that were included in the analyses. The N. gonorrhoeae strains studied were ATCC 19424 and ATCC 49226, as well as clinical strains NG 3, NG 7, NG 12, NG 14, NG 19, NG 20, NG 21, and NG 22, and WHO reference strains NCTC 13820 (WHO X), NCTC 13821 (WHO Y), and NCTC 13822 (WHO Z). Please refer to Table 1 for drug abbreviations. Italicized values indicate low Pearson correlation coefficients (ρ). a To determine an estimated correlation, all values below 0.002 were rounded to 0.001.
Table 2.
Changes in the susceptibilities of in vitro transformants of the receptor strain FA 1090 with different penA alleles.
Table 3.
Impact of the efflux pump inhibitor CCCP on the minimum inhibitory concentrations of azithromycin, piperacillin, tazobactam, and piperacillin/tazobactam examined in the studied strains.
Table 4.
Impact of the mtrD gene inactivation on the minimum inhibitory concentrations in the studied strains.