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

References

  1. Accou-Demartin M., Gaborieau V., Song Y., Roumagnac P., Marchou B., Achtman M., Weill F.-X. Salmonella enterica Serotype Typhi with nonclassical quinolone resistance phenotype. Emerg. Infect. Dis., 2011, vol. 17, no. 6, pp. 1091—1094. doi: 10.3201/eid1706.101242
  2. Achtman M., Wain J., Weill F.-X., Nair S., Zhou Z., Sangal V., Krauland M.G., Hale J.L., Harbottle H., Uesbeck A., Dougan G., Harrison L.H., Brisse S., S. Enterica MLST Study Group. Multilocus sequence typing as a replacement for serotyping in Salmonella enterica. PLoS Pathogens, 2012, vol. 8, no. 6: e1002776. doi: 10.1371/journal.ppat.1002776
  3. Ahamed Riyaaz A.A., Perera V., Sivakumaran S., de Silva N. Typhoid fever due to extended spectrum P-lactamase-producing Salmonella enterica serovar Typhi: a case report and literature review. Case Reports in Infect. Dis., 2018: 4610246. doi: 10.1155/2018/4610246
  4. Akinyemi K.O., Iwalokun B.A., Alafe O.O., Mudashiru S.A., Fakorede C. blaCTX-M-I group extended spectrum beta lactamase-producing Salmonella typhi from hospitalized patients in Lagos, Nigeria. Infect. Drug. Resist., 2015, vol. 11, no. 8, pp. 99—106. doi: 10.2147/IDR.S78876
  5. Akinyemi K.O., Iwalokun B.A., Oyefolu A.O., Fakorede C.O. Occurrence of extended-spectrum and AmpC P-lactamases in multiple drug resistant Salmonella isolates from clinical samples in Lagos, Nigeria. Infect. Drug. Resist., 2017, vol. 10, pp. 19—25. doi: 10.2147/IDR.S123646
  6. Al Naiemi N., Zwart B., Rijnsburger M.C., Roosendaal R., Debets Ossenkopp Y.J., Mulder J.A., Fijen C.A., Maten W., Vandenbroucke-Grauls C.M., Savelkoul P.H. Extended-spectrum-beta-lactamase production in a Salmonella enterica serotype Typhi strain from the Philippines. J. Clin. Microbiol., 2008, vol. 46, pp. 2794—2795. doi: 10.1128/JCM.00676-08
  7. Baltazar M., Ngandjio A., Holt K.E., Lepillet E., Pardos de la Gandara M., Collard J.M., Bercion R., Nzouankeu, A., Le Hello S., Dougan G., Fonkoua M.C., Weill F.-X. Multidrug-resistant Salmonella enterica serotype Typhi, Gulf of Guinea Region, Africa. Emerg. Infect. Dis., 2015, vol. 21, no. 4, pp. 655— 659. doi: 10.3201/eid2104.141355
  8. CDC. National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS): Human Isolates Surveillance Report for 2015 (Final Report). Atlanta, Georgia: U.S. Department of Health and Human Services, CDC, 2018.
  9. Chau T.T., Campbell J.I., Galindo C.M., Van Minh Hoang N., Diep T.S., Nga T.T., Van Vinh Chau N., Tuan P.Q., Page A.L., Ochiai R.L., Schultsz C., Wain J., Bhutta Z.A., Parry C.M., Bhattacharya S.K., Dutta S., Agtini M., Dong B., Honghui Y., Anh D.D., Canh do G., Naheed A., Albert M.J., Phetsouvanh R., Newton P.N., Basnyat B., Arjyal A., La T.T., Rang N.N., Phuong le T., Van Be Bay P., von Seidlein L., Dougan G., Clemens J.D., Vinh H., Hien T.T., Chinh N.T., Acosta C.J., Farrar J., Dolecek C. Antimicrobial drug resistance of Salmonella enterica serovar typhi in Asia and molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob. Agents Chemother, 2007, vol. 51, no. 12, pp. 4315—4323. doi: 10.1128/AAC.00294-07
  10. Crump J.A., Luby S.P., Mintz E.D. The global burden of typhoid fever. Bull. World Health Organ, 2004, vol. 82, pp. 346—353.
  11. Crump J.A., Kretsinger K., Gay K. Clinical response and outcome of infection with Salmonella enterica serotype Typhi with decreased susceptibility to fluoroquinolones: a United States FoodNet multicentre retrospective study. Antimicrob. Agents Chemother., 2008, vol. 52, pp. 1278-1284. doi: 10.1128/AAC.01509-07
  12. Dolecek C., Tran T.P., Nguyen N.R., Le T.P., Ha V., Phung Q.T., Doan C.D., Nguyen T.B., Duong T.L., Luong B.H., Nguyen T.B., Nguyen T.A., Pham N.D., Mai N.L., Phan V.B., Vo A.H., Nguyen V.M., Tran T.T., Tran T.C., Schultsz C., Dunstan S.J., Stepniewska K., Campbell J.I., To S.D., Basnya, B., Nguyen V.V., Nguyen V.S., Nguyen T.C., Tran T.H., Farrar J. A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. PLoS One, 2008, vol. 3, no. 5: e2188. doi: 10.1371/journal.pone.0002188
  13. Effa E.E., Bukirwa H. Azithromycin for treating uncomplicated typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst. Rev, 2011, vol. 10: CD006083. doi: 10.1002/14651858.CD006083.pub3
  14. Effa E.E., Lassi Z.S., Critchley J.A., Garner P., Sinclair D., Olliaro P.L., Bhutta Z.A. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database Sys.t Rev., 2011, vol. 10: CD004530. doi: 10.1002/14651858.CD004530.pub4
  15. Geetha V.K., Yugendran T., Srinivasan R., Harish B.N. Plasmid-mediated quinolone resistance in typhoidal Salmonellae: a preliminary report from South India. Indian J. Med. Microbiol., 2014, vol. 32:pp. 31-34. doi: 10.4103/0255-0857.124292
  16. Gokul B.N., Godfred A. Menezes G.A., Belgode N., Harish B.N. ACC-1 P-Lactamase— producing Salmonella enterica Serovar Typhi, India. Emerg. Infect. Dis, 2010, vol. 16, no. 7, pp. 1170-1171. doi: 10.3201/eid1607.091643
  17. Gonzalez-Lopez J., Piedra-Carrasco N., Salvador F., Rodriguez V., Sanchez-Montalva A., Planes A.M., Molina I., Larrosa M.N. ESBL-producing Salmonella enterica serovar Typhi in traveler returning from Guatemala to Spain. Emerg. Infect. Dis., 2014, vol. 20, no. 11,pp. 1918-1920. doi: 10.3201/eid1607.091643
  18. Gul D., Potter R.F., Riaz H., Ashraf S.T., Wallace M.A., Munir T., Ali A., Burnham C.-A., Dantas G., Andleeb S. Draft genome sequence of a Salmonella enterica serovar Typhi strain resistant to fourth-generation cephalosporin and fluoroquinolone antibiotics. Genome Announc., 2017, vol. 5, no. 42: e00850—17. doi: 10.1128/genomeA.00850-17
  19. Gupta R., Gaind R., Wain J., Deb M., Singh L.C., Basir S.F. Characterization of non-classical quinolone resistance in Salmonella enterica serovar Typhi: Report of a novel mutation in gyrB gene and diagnostic challenges. Biomol. Detect. Quantif, 2015, vol. 2, pp. 30-34. doi: 10.1016/j.bdq.2015.01.003
  20. Hendriksen R.S., Leekitcharoenphon P., Mikoleit M., Jensen J.D., Kaas R.S., Roer L., Joshi H.B., Pornruangmong S., Pulsrikarn C., Gonzalez-Aviles G.D., Reuland E.A., Al Naiemi N., Wester A.L., Aarestrup F.M., Hasman H. Genomic dissection of travel-associated extended-spectrum-beta-lactamase-producing Salmonella enterica serovar typhi isolates originating from the Philippines: a one-off occurrence or a threat to effective treatment of typhoid fever? J. Clin. Microbiol., 2015, vol. 53, no. 2, pp. 677-680. doi: 10.1128/JCM.03104-14
  21. Holt K.E., Parkhill J., Mazzoni C.J., Roumagnac P., Weill F.-X., Goodhead I., Rance R., Baker S., Maskell D.J., Wain J., Dolecek C., Achtman M., Dougan G. High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi. Nat. Genet., 2008, vol. 40, no. 8, pp. 987-993. doi: 10.1038/ng.195
  22. International Typhoid Consortium, Wong V.K., Holt K.E., Okoro C., Baker S., Pickard D.J., Marks F., Page A.J., Olanipekun G., Munir H., Alter R., Fey P.D., Feasey N.A., Weill F.-X., Le Hello S., Hart P.J., Kariuki S., Breiman R.F., Gordon M.A., Heyderman R.S., Jacobs J., Lunguya O., Msefula C., MacLennan C.A., Keddy K.H., Smith A.M., Onsare R.S., De Pinna E., Nair S., Amos B., Dougan G., Obaro S. Molecular surveillance identifies multiple transmissions of typhoid in West Africa. PLoS Negl. Trop. Dis., 2016, vol. 10, no. 9: e0004781. doi: 10.1371/journal.pntd.0004781
  23. Keddy K.H, Smith A.M, Sooka A., Ismail H., Oliver S. Fluoroquinolone-resistant typhoid, South Africa. Emerg. Infect. Dis., 2010, vol. 16,pp. 879-880. doi: 10.3201/eid1605.091917
  24. Kidgell C., Reichard U., Wain J., Linz B., Torpdahl M., Dougan G. Salmonella Typhi, the causative agent of typhoid fever, is approximately 50,000 years old. Infect. Genet. Evol., 2002, vol. 2, no. 1, pp. 39-45. doi: 10.1016/S1567-1348(02)00089-8
  25. Kothari A., Pruthi A., Chugh T.D. The burden of enteric fever. J. Infect. Dev. Ctries., 2008, vol. 2, no. 4, pp. 253-259. doi: 10.3855/jidc.218
  26. Kuijpers L., Phe T., Veng C.H., Lim K., Ieng S., Kham C., Fawal N., Fabre L., Le Hello S., Vlieghe E., Weill F.-X., Jacobs J., Peetermans W.E. The clinical and microbiological characteristics of enteric fever in Cambodia, 2008—2015. PLoS Negl. Trop. Dis., 2017, vol. 11, no. 9: e0005964. doi: 10.1371/journal.Pntd.0005964
  27. Kuleshov K.V., Kostikova A., Pisarenko S.V., Kovalev D.A., Tikhonov S.N., Savelieva I.V., Saveliev V.N., Vasilieva O.V., Zinich L.S., Pidchenko N.N., Kulichenko A.N., Shipulin G.A. Comparative genomic analysis of two isolates of Vibrio cholerae O1 Ogawa El Tor isolated during outbreak in Mariupol in 2011. Infect. Genet. Evol., 2016, vol. 44, pp. 471-478. doi: 10.1016/j.meegid.2016.07.039
  28. Matono T., Morita M., Yahara K., Lee K., Izumiya H., Kaku M., Ohnishi M. Emergence of resistance mutations in Salmonella enterica serovar Typhi against fluoroquinolones. Open Forum Infect. Dis., 2017, vol. 4, no. 4: ofx230. doi: 10.1093/ofid/ofx230
  29. Mirza S., Beeching N., Hart C. Multi-drug resistant typhoid: a global problem. J. Med. Microbial, 1996, vol. 44, pp. 317-319. doi: 10.1099/00222615-44-5-317
  30. Nuesch-Inderbinen M., Abgottspon H., Sagesser G., Cernela N., Stephan R. Antimicrobial susceptibility of travel-related Salmonella enterica serovar Typhi isolates detected in Switzerland (2002—2013) and molecular characterization of quinolone resistant isolates. BMC Infect. Dis., 2015, vol. 15:212. doi: 10.1186/s12879-015-0948-2
  31. Okanda T., Haque A., Ehara T., Huda Q., Ohkusu K., Miah R.A., Matsumoto T. Characteristics of resistance mechanisms and molecular epidemiology of fluoroquinolone-nonsusceptible Salmonella enterica serovar Typhi and Paratyphi A isolates from a Tertiary Hospital in Dhaka, Bangladesh. Microb. Drug. Resist., 2018, vol. 24, no. 10. doi: 10.1089/mdr.2018.0039
  32. Park C.H., Robicsek A., Jacoby G.A., Sahm D., Hooper D.C. Prevalence in the United States of aac(6’)-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob. Agents Chemother., 2006, vol 50, no. 11, pp. 3953-3955. doi: 10.1128/AAC.00915-06
  33. Parry C.M., Thieu N.T.V., Dolecek C., Karkey A., Gupta R., Turner P., Dance D., Maude R.R., Ha V., Tran C.N., Thi P.L., Be B.P.V., Phi L.T.T., Ngoc R.N., Ghose A., Dongol S., Campbell J.I., Thanh D.P., Thanh T.H., Moore C.E., Sona S., Gaind R., Deb M., Anh H.V., Van S.N., Tinh H.T., Day N.P., Dondorp A., Thwaites G., Faiz M.A., Phetsouvanh R., Newton P., Basnyat B., Farrar J.J., Baker S. Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A. Antimicrob. Agents Chemother., 2015, vol. 59, no. 5, pp. 2756-2764. doi: 10.1128/AAC.04729-14
  34. Pfeifer Y., Matten J., Rabsch W. Salmonella enterica serovar Typhi with CTX-M P-lactamase, Germany. Emerg. Infect. Dis., 2009, vol. 15, pp. 1533-1535. doi: 10.3201/eid1509.090567
  35. Phoba M.F., Barbe B., Lunguya O., Masendu L., Lulengwa D., Dougan G., Wong V.K., Bertrand S., Ceyssens P.J., Jacobs J., Van Puyvelde S., Deborggraeve S. Salmonella enterica serovar Typhi producing CTX-M-15 extended spectrum P-lactamase in the Democratic Republic of the Congo. Clin. Infect. Dis, 2017, vol. 65, no. 7, pp. 1229-1231. doi: 10.1093/cid/cix342
  36. Pokharel B.M., Koirala J., Dahal R.K., Mishra S.K., Khadga P.K., Tuladhar N.R. Multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing Salmonella enterica (serotypes Typhi and Paratyphi A) from blood isolates in Nepal: surveillance of resistance and a search for newer alternatives. Int. J. Infect. Dis., 2006, vol. 10, no. 6,pp. 434-438. doi: 10.1016/j.ijid.2006.07.001
  37. Ramachandran A., Shanthi M., Sekar U. Detection of blaCTX-M extended spectrum beta-lactamase producing Salmonella enterica serotype Typhi in a tertiary care centre. J. Clin. Diagn. Res, 2017, vol. 11, no. 9: DC21-DC24. doi: 10.7860/JCDR/2017/30150.10637
  38. Robicsek A., Strahilevitz J., Sahm D.F., Jacoby G.A., Hooper D.C. Qnr prevalence in ceftazidime-resistant Enterobacteriacae isolates from the United States. Antim. Agents Chemot., 2006, vol. 50, no. 8, pp. 2872-2874. doi: 10.1128/AAC.01647-05
  39. Rodrigues C., Kapil A., Sharma A., Devanga Ragupathi N.K., Inbanathan F.Y., Veeraraghavan B., Kang G. Whole genome shotgun sequencing of cephalosporin-resistant Salmonella enterica serovar Typhi. Genome Announc., 2017, vol. 5: e01639-16. doi: 10.1128/genomeA.01639-16
  40. Rotimi V., Jamal W., Pal T., Sovenned A., John Albert M. Emergence of CTX-M-15 type extended-spectrum b-lactamase-pro-ducing Salmonella spp. in Kuwait and the United Arab Emirates. J. Med. Microbiol., 2008, vol. 57, pp. 881-886. doi: 10.1099/jmm.0.47509-0
  41. Roumagnac P., Weill F.-X., Dolecek C., Baker S., Brisse S., Chinh N.T., Le T.A., Acosta C.J., Farrar J., Dougan G., Achtman M. Evolutionary history of Salmonella Typhi. Science, 2006, vol. 314, no. 5803, pp. 1301—1304. doi: 10.1126/science.1134933
  42. Song Y., Roumagnac P., Weill F.-X., Wain J., Dolecek C., Mazzoni C.J., Holt K.E., Achtman M. A multiplex single nucleotide polymorphism typing assay for detecting mutations that result in decreased fluoroquinolone susceptibility in Salmonella enterica serovars Typhi and Paratyphi A. J. Antimicrob. Chemoth., 2010, vol. 65, no. 8, pp. 1631—1641. doi: 10.1093/jac/dkq175
  43. Tadesse G., Tessema T.S., Beyene G., Aseffa A. Molecular epidemiology of fluoroquinolone resistant Salmonella in Africa: a systematic review and meta-analysis. PLoS One, 2018, vol. 13, no. 2: e0192575. doi: 10.1371/journal.pone.0192575
  44. Thompson C.N., Karkey A., Dongol S., Arjyal A., Wolbers M., Darton T., Farrar J.J., Thwaites G.E., Dolecek C., Basnyat B., Baker S. Treatment response in enteric fever in an era of increasing antimicrobial resistance: an individual patient data analysis of 2092 participants enrolled into 4 randomized, controlled trials in Nepal. Clin. Infect. Dis., 2017, vol. 64, no. 11, pp. 1522—1531. doi: 10.1093/cid/cix185
  45. Weill F.-X. La fievre typhoide n’est plus aussi simple a soigner. Med. Sci., 2010, vol. 26, pp. 969—975. doi: 10.1051/med-sci/20102611969
  46. Wong V.K., Baker S., Pickard, D.J., Parkhill J., Page A.J., Feasey N.A., Kingsley R.A., Thomson, N.R., Keane J.A., Weill F.-X., Edwards D.J., Hawkey J., Harris S.R., Mather A.E., Cain A.K., Hadfield J., Hart P.J., Thieu N.T., Klemm E.J., Glinos D.A., Breiman R.F., Watson C.H., Kariuki S., Gordon M.A., Heyderman R.S., Okoro C., Jacobs J., Lunguya O., Edmunds W.J., Msefula C., Chabalgoity J.A., Kama M., Jenkins K., Dutta S., Marks F., Campos J., Thompson C., Obaro S., MacLennan C.A., Dolecek C., Keddy K.H., Smith A.M., Parry C.M., Karkey A., Mulholland E.K., Campbell J.I., Dongol S., Basnyat B., Dufour M., Bandaranayake D., Naseri T.T., Singh S.P., Hatta M., Newton P., Onsare, R.S., Isaia L., Dance D., Davong V., Thwaites G., Wijedoru L., Crump J.A., De Pinna E., Nair S., Nilles E.J., Thanh D.P., Turner P., Soeng S., Valcanis M., Powling J., Dimovski K., Hogg G., Farrar J., Holt K.E., Dougan G. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter-and intracontinental transmission events. Nat. Genet., 2015, vol. 47, no. 6, pp. 632—641. doi: 10.1038/ng.3281
  47. Wong V.K., Baker S., Connor T.R., Pickard D., Page A.J., Dave J., Murphy N., Holliman R., Sefton A., Millar M., Dyson Z.A., Dougan G., Hol K.E., International Typhoid Consortium. An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid. Nat. Commun., 2016, vol. 7:12827. doi: 10.1038/ncomms12827
  48. World Health Organization (WHO). The diagnosis, treatment and prevention of typhoid fever. WHO/V&B/03.07. Geneva: WHO; 2003

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