Unique combined penA/mtrR/porB mutations and NG-MAST strain types associated with ceftriaxone and cefixime MIC increases in a 'susceptible' Neisseria gonorrhoeae population

Journal of Antimicrobial Chemotherapy

Volumn 69, Issue 6, 2014, Pages 1510-1516

  Thakur, S D ^a   Starnino, S ^b   Horsman, G B ^c   Levett, P N ^c   Dillon, J R ^a,b  

^a UNIVERSITY OF SASKATCHEWAN   (Canada)

^b UNIVERSITY OF SASKATCHEWAN   (Canada)

^c Saskatchewan Disease Control Laboratory   (Canada)

Author keywords

Antimicrobial resistance mechanisms; Extended spectrum cephalosporins; Gonorrhoea

Indexed keywords

CEFIXIME; CEFTRIAXONE; MULTIPLE TRANSFER RESISTANCE REPRESSOR; PENICILLIN BINDING PROTEIN; PENICILLIN BINDING PROTEIN 2; PORIN; PORIN B; REPRESSOR PROTEIN; UNCLASSIFIED DRUG; BACTERIAL PROTEIN;

ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL GENE; BACTERIAL STRAIN; BACTERIUM ISOLATE; CONTROLLED STUDY; DNA SEQUENCE; FEMALE; GENE MUTATION; HUMAN; MALE; MINIMUM INHIBITORY CONCENTRATION; MTRR GENE; NEISSERIA GONORRHOEAE; NONHUMAN; PENA GENE; PORB GENE; PROMOTER REGION; AMINO ACID SUBSTITUTION; ANTIBIOTIC RESISTANCE; CANADA; DRUG EFFECTS; GENETICS; GONORRHEA; MICROBIAL SENSITIVITY TEST; MICROBIOLOGY; MUTATION;

AMINO ACID SUBSTITUTION; BACTERIAL PROTEINS; CANADA; CEFIXIME; CEFTRIAXONE; DRUG RESISTANCE, BACTERIAL; FEMALE; GONORRHEA; HUMANS; MALE; MICROBIAL SENSITIVITY TESTS; MUTATION; NEISSERIA GONORRHOEAE;

EID: 84897788741     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkt543     Document Type: Article

References (41)

1. WHO. Global Action Plan to Control the Spread and Impact of Antimicrobial Resistance in Neisseria gonorrhoeae. Geneva: WHO, 2012.
2. Ohnishi M, Saika T, Hoshina S et al. Ceftriaxone-resistant Neisseria gonorrhoeae, Japan. Emerg Infect Dis 2011; 17: 148-9.
3. Unemo M, Golparian D, Nicholas R et al. High-level cefixime-and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother 2012; 56: 1273-80.
4. Allen VG, Mitterni L, Seah C et al. Neisseria gonorrhoeae treatment failure and susceptibility to cefixime in Toronto, Canada. JAMA 2013; 309: 163-70.
5. Public Health Agency of Canada. Reported Cases and Rates of Gonorrhea by Province/Territory and Sex, 1980 to 2009. Ottawa: Public Health Agency of Canada, 2011. http://www.catie.ca/sites/default/files/2009% 20Report%20on%20STI%20in%20Canada_EN.pdf (13 September 2013, date last accessed).
6. Martin I, Jayaraman G, Wong T et al. Trends in antimicrobial resistance in Neisseria gonorrhoeae isolated in Canada: 2000-2009. Sex Transm Dis 2011; 38: 892-8.
7. Public Health Agency of Canada. Canadian Guidelines on Sexually Transmitted Infections. Ottawa: Public Health Agency of Canada, 2008. http://library.catie.ca/PDF/ATI-20000s/26024.pdf (10 September, date last accessed).
8. Chisholm SA, Mouton JW, Lewis DA et al. Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink? J Antimicrob Chemother 2010; 65: 2141-8.
9. Martin I, Sawatzky P, Allen V et al. Emergence and characterization of Neisseria gonorrhoeae isolates with decreased susceptibilities to ceftriaxone and cefixime in Canada: 2001-2010. Sex Transm Dis 2012; 39: 316-23.
10. Zhao S, Duncan M, Tomberg J et al. Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. Antimicrob Agents Chemother 2009; 53: 3744-51.
11. Ohnishi M, Golparian D, Shimuta K et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea? Detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother 2011; 55: 3538-45.
12. Ameyama S, Onodera S, Takahata M et al. Mosaic-like structure of penicillin-binding protein 2 gene (penA) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime. Antimicrob Agents Chemother 2002; 46: 3744-9.
13. Whiley DM, Limnios EA, Ray S et al. Diversity of penA alterations and subtypes in Neisseria gonorrhoeae strains from Sydney, Australia, that are less susceptible to ceftriaxone. Antimicrob Agents Chemother 2007; 51: 3111-6.
14. Powell AJ, Tomberg J, Deacon AM et al. Crystal structures of penicillin-binding protein 2 from penicillin susceptible and resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. J Biol Chem 2009; 284: 1202-12.
15. Lee SG, Lee H, Jeong SH et al. Various penA mutations together with mtrR, porB and ponA mutations in Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone. J Antimicrob Chemother 2010; 65: 669-75.
16. Liao M, Gu MM, Yang Y et al. Analysis of mutations in multiple loci of Neisseria gonorrhoeae isolates reveals effects of PIB, PBP2 and MtrR on reduced susceptibility to ceftriaxone. J Antimicrob Chemother 2011; 66: 1016-23.
17. Tomberg J, Unemo M, Davies C et al. Molecular and structural analysis of mosaic variants of penicillin-binding protein 2 conferring decreased susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae: role of epistatic mutations. Biochemistry 2010; 49: 8062-70.
18. Veal WL, Nicholas RA, Shafer WM. Overexpression of the MtrCMtrD-MtrE efflux pump due to an mtrR mutation is required for chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. J Bacteriol 2002; 184: 5619-24.
19. Olesky M, Hobbs M, Nicholas RA. Identification and analysis of amino acid mutations in porin IB that mediate intermediate-level resistance to penicillin and tetracycline in Neisseria gonorrhoeae. Antimicrob Agents Chemother 2002; 46: 2811-20.
20. Whiley DM, Goire N, Lambert SB et al. Reduced susceptibility to ceftriaxone in Neisseria gonorrhoeae is associated with mutations G542S, P551S and P551L in the gonococcal penicillin-binding protein 2. J Antimicrob Chemother 2010; 65: 1615-8.
21. Allen VG, Farrell DJ, Rebbapragada A et al. Molecular analysis of antimicrobial resistance mechanisms in Neisseria gonorrhoeae isolates from Ontario, Canada. Antimicrob Agents Chemother 2011; 55: 703-12.
22. Thakur SD, Nagle E, Levett P et al. Isolates of Neisseria gonorrhoeae from Saskatchewan are susceptible to most antibiotics except tetracycline. In: Abstracts of the Seventy-eighth Annual Conference of the Canadian Association for Clinical Microbiology and Infectious Diseases, Edmonton, AB, 2010. Abstract SP-25, p. 27. Canadian Association for Clinical Microbiology and Infectious Diseases, Winnipeg, Manitoba, Canada.
23. Thakur SD, Nagle E, Levett PN et al. Emerging molecular mutations of reduced susceptibility to third-generation cephalosporins in Neisseria gonorrhoeae isolates from Saskatchewan, Canada. Sex Transm Infect 2011; 87: A115-6 (doi:10.1136/sextrans-2011-050108.40).
24. Martin I, Ison C, Aanensen D et al. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis 2004; 189: 1497-505.
25. Knapp JS. Historical perspectives and identification of Neisseria and related species. Clin Microbiol Rev 1988; 1: 415-31.
26. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Nineteenth Informational Supplement M100-S19. CLSI, Wayne, PA, USA, 2009.
27. World Health Organization Western Pacific Gonococcal Antimicrobial Surveillance Programme. Surveillance of antimicrobial resistance of Neisseria gonorrhoeae in the WHO Western Pacific region, 1992-1994. Genitourin Med 1997; 73: 355-61.
28. Unemo M, Fasth O, Fredlund H et al. Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes. J Antimicrob Chemother 2009; 63: 1142-51.
29. Vidovic S, Thakur SD, Horsman GB et al. Longitudinal analysis of the evolution and dissemination of Neisseria gonorrhoeae strains (Saskatchewan, Canada 2005-2008) reveals three major circulating strains and convergent evolution of ciprofloxacin and azithromycin resistance. J Clin Microbiol 2012; 50: 3823-30.
30. Warner DM, Shafer MW, Jerse AE. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol Microbiol 2008; 70: 462-78.
31. Yates F. Contingency tables involving small numbers and the x2 test. J Royal Stat Soc 1934; 1: 217-35.
32. Lindberg R, Fredlund H, Nicholas R et al. Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime and ceftriaxone: association with genetic polymorphisms in penA, mtrR, porB1b, and ponA. Antimicrob Agents Chemother 2007; 51: 2117-22.
33. Hagman KE, Shafer WM. Transcriptional control of the mtr efflux system of Neisseria gonorrhoeae. J Bacteriol 1995; 177: 4162-5.
34. Shafer WM, Balthazar JT, Hagman KE et al. Missense mutations that alter the DNA-binding domain of the MtrR protein occur frequently in rectal isolates of Neisseria gonorrhoeae that are resistant to faecal lipids. Microbiology 1995; 141: 907-11.
35. Sachdev D, Kumari I, Chopra M et al. Understanding the molecular mechanisms of MtrR in the regulation of antimicrobial resistance in Neisseria gonorrhoeae using in vitro and in silico studies. Sex Trans Infect 2013; 89 Suppl 1: A68.
36. Ilina EN, Vereshchagin VA, Borovskaya AD et al. Relation between genetic markers of drug resistance and susceptibility profile of clinical Neisseria gonorrhoeae strains. Antimicrob Agents Chemother 2008; 52: 2175-82.
37. Spratt BG. Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae. Nature 1998; 332: 173-6.
38. Pan W, Spratt BG. Regulation of the permeability of the gonococcal cell envelope by the mtr system. Mol Microbiol 1994; 11: 769-75.
39. Carbonetti NH, Sparling PF. Molecular cloning and characterization of the structural gene for protein I, the major outer membrane protein of Neisseria gonorrhoeae. Gene 1987; 84: 9084-8.
40. Xia M, Whittington WL, Shafer WM et al. Gonorrhea among men who have sex with men: outbreak caused by a single genotype of erythromycin-resistant Neisseria gonorrhoeae with a single-base pair deletion in the mtrR promoter region. J Infect Dis 2000; 181: 2080-2.
41. Gotschlich EC, SeiffME, Blake MS et al. Porin protein of Neisseria gonorrhoeae: cloning and gene structure. Proc Natl Acad Sci USA 1987; 84: 8135-39.