The antimicrobial susceptibility, resistance mechanisms and phylogenetic structure of S. Typhi isolated in 2005-2018 in the Russian Federation

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Abstract

Here we present current global epidemiological and microbiological trends for typhoid fever, as well as describe antimicrobial susceptibility and resistance mechanisms of S. Typhi. The data on examining 299 S. Typhi isolates collected in 2005—2018 in the Russian Federation were analyzed from the Russian S. Typhi Reference Center. It was found that S. Typhi population consisted of the isolates with different resistance phenotypes and mechanisms as well as genetic heterogeneity. Moreover, antimicrobial susceptibility was detected in as low as 10.4% S. Typhi strains, whereas 89.6% isolates showed fluoroquinolone resistance (including 7.3% high-level resistance) and 3.0% — multidrug resistance to am-picillin, chloramphenicol, trimethoprim/sulfamethoxazole, tetracycline and fluoroquinolones. All strains preserved susceptibility to extended-spectrum cephalosporins and azithromycin. Fluoroquinolone low-level resistance in S. Typhi was due to single nucleotide substitutions in the gyrA: Asp87Asn (78.7%) Ser83Tyr (5.0%) and Ser83Phe (3.2%). In addition, a plasmid-mediated low-level fluoroquinolone resistance (qnrS) was found in one isolate. In contrast, a fluoroquinolone high-level resistance in S. Typhi was due to accumulation of three single nucleotide substitutions in the genes gyrA (Asp87Asn+Ser83Phe) andparC (Ser80Ile). In multidrug resistant S. Typhi isolates, pHCMl plasmids of incompatibility group IncHI1B(R27) (consisted of blaTEM.1, catA1, dfrA7 and tetB) and single nucleotide substitutions Ser83Tyr or Asp87Asn in gene gyrA were detected. The data of phylogenetic reconstruction based on the analysis of core singlenucleotide variations among examined and previously sequenced S. Typhi genomes, demonstrated that more than 80.0% of S. Typhi isolated in Russia were referred to the Asian genotype as they belonged to subclade 4.3.1 (by Wong et al.) or dominant H58 clade (H58 haplotype by Roumagnac et al.). More than 60.0% isolates in this dominant phylogenetic group possessed a fluoroquinolone low-level resistance due to gyrA Asp87Asn. Less than 20.0% of S. Typhi strains isolated in Russia phylogenetically belonged to the subclades other than 4.3.1 (non-H58) and differed from the major S. Typhi population by lacked antibiotic resistance or exerted fluoroquinolone resistance due to gyrA Ser83Phe. The study data allowed to expand our understanding on genetic diversity in S. Typhi strains isolated recently and pinpoint features of phylogenetic structure for S. Typhi population in the Russian Federation.

About the authors

S. A. Egorova

Saint-Petersburg Pasteur Institute

Author for correspondence.
Email: egorova72@mail.ru
ORCID iD: 0000-0002-7589-0234

Egorova Svetlana Alexanrovna - PhD (Medicine), Senior Researcher, Laboratory of Enteric Infections.

St. Petersburg, SPIN 4000-4122

Russian Federation

K. V. Kuleshov

Federal budget institute of science "Central research institute for epidemiology" Federal service for surveillance consumers' rights protection and human well-being.

Email: konstantinkul@gmail.com
ORCID iD: 0000-0002-5238-7900

Kuleshov Konstantin V. - PhD (Biology), Senior Researcher, Laboratory of Enteric Diseases Epidemiology and Molecular Diagnostic.

Moscow, SPIN: 7404-4080  

Russian Federation

L. A. Kaftyreva

Saint-Petersburg Pasteur Institute;
North-Western state medical University named after I.I. Mechnikov

Email: kaflidia@mail.ru
ORCID iD: 0000-0003-0989-1404

Kaftyreva Lidiia A. - PhD, MD (Medicine), Professor, Head of the Laboratory of Enteric Infections, St. PPI.

St. Petersburg, SPIN: 6721-7873  

Russian Federation

Zoya N. Matveeva

Saint-Petersburg Pasteur Institute

Email: egorova72@mail.ru

Matveeva Zoya N. - PhD (Medicine), Leading Researcher, Laboratory of Enteric Infections.

St. Petersburg, SPIN: 5094-5749

Russian Federation

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