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. 2023 Jan 13;12(1):170.
doi: 10.3390/antibiotics12010170.

Azithromycin Susceptibility Testing and Molecular Investigation of Neisseria gonorrhoeae Isolates Collected in Russia, 2020-2021

Ilya Kandinov  1 , Boris Shaskolskiy  1 , Dmitry Kravtsov  1 , Alexandra Vinokurova  1 , Sofya Gorshkova  1 , Alexey Kubanov  2 , Victoria Solomka  2 , Julia Shagabieva  2 , Dmitry Deryabin  2 , Ekaterina Dementieva  1 , Dmitry Gryadunov  1
Affiliations

Azithromycin Susceptibility Testing and Molecular Investigation of Neisseria gonorrhoeae Isolates Collected in Russia, 2020-2021

Ilya Kandinov et al. Antibiotics (Basel). .

Abstract

The aim of this work was to study the resistance to macrolides (azithromycin) in the modern Russian population of N. gonorrhoeae with the analysis of genetic resistance determinants. Azithromycin is not used to treat gonococcal infection in Russia. However, among 162 isolates collected in 2020-2021, 22 isolates (13.6%) were phenotypically resistant to azithromycin. Mutations in 23S rRNA genes were found only in two isolates; erm and mefA genes were absent. Azithromycin resistance was shown to be predominantly associated with mutations in the mtrR and mtrD genes of the MtrCDE efflux pump and their mosaic alleles which may have formed due to a horizontal transfer from N. meningitidis. A total of 30 types of mtrR alleles and 10 types of mtrD alleles were identified including mosaic variants. Matching between the mtrR and mtrD alleles was revealed to indicate the cooperative molecular evolution of these genes. A link between the mtrR and mtrD alleles and NG-MAST types was found only for NG-MAST 228 and 807, typical of N. gonorrhoeae in Russia. The high level of resistance to azithromycin in Russia may be related to the spread of multiple transferable resistance to antimicrobials regardless of their use in the treatment of gonococcal infection.

Keywords: Neisseria gonorrhoeae; azithromycin resistance; efflux pump; mtrR and mtrD alleles; resistance determinants.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Amino acid sequences of mtrR (a) and mtrD (b) alleles in N. gonorrhoeae isolates collected in the Russian Federation in 2020–2021 in comparison with the wild type (WT) mtrR (NG-STAR “Allele 353”) and mtrD (PubMLST “Allele 640”) sequences. Designations: ‘+’ – presence of deletion/ MG-like promoter; ‘–‘ – absence of deletion/ MG-like promoter.
Figure 2
Figure 2
Correspondence between mtrR and mtrD cladograms constructed independently for the Russian N. gonorrhoeae isolates collected in 2020–2021. Sample numbers and the mtrR or mtrD allele numbers are indicated on the branches. Matched clades are formed by linked leaves of the phylogenetic tree. Matched clades consisting of five or more isolates are painted in different colors.
Figure 3
Figure 3
Box plot: MICAzm in groups of N. gonorrhoeae isolates with different genetic profiles. A description of the profiles by group is given in Table 1. Thick solid lines in each box indicate the median MICAzm value for each group. The whiskers extend to the boundaries of the interquartile range. The dotted line indicates the EUCAST breakpoint for azithromycin resistance.
Figure 4
Figure 4
Maximum likelihood phylogenetic distance tree for concatenated mtrR and mtrD gene sequences of the N. gonorrhoeae isolates collected in Russia in 2020–2021. Isolate numbers are colored according to groups I-VII (Table 1, Figure 3). Bootstrap values of 70 or more are colored in red.
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