1887

Abstract

Numerous aminoglycoside resistance genes have been reported in Campylobacter spp. often resembling those from Gram-positive bacterial species and located in transferable genetic elements with other resistance genes. We discovered a new streptomycin (STR) resistance gene in Campylobacter coli showing 27–34 % amino acid identity to aminoglycoside 6-nucleotidyl-transferases described previously in Campylobacter. STR resistance was verified by gene expression and insertional inactivation. This ant-like gene differs from the previously described aminoglycoside resistance genes in Campylobacter spp. in several aspects. It does not appear to originate from Gram-positive bacteria and is located in a region corresponding to a previously described hypervariable region 14 of C. jejuni with no other known resistance genes detected in close proximity. Finally, it does not belong to a multiple drug resistance plasmid or transposon. This novel ant-like gene appears widely spread among C. coli as it is found in strains originating both from Europe and the United States and from several, apparently unrelated, hosts and environmental sources. The closest homologue (60 % amino acid identity) was found in certain C. jejuni and C. coli strains in a similar genomic location, but an association with STR resistance was not detected. Based on the findings presented here, we hypothesize that Campylobacter ant-like gene A has originated from a common ancestral proto-resistance element in Campylobacter spp., possibly encoding a protein with a different function. In conclusion, whole genome sequencing allowed us to fill in a knowledge gap concerning STR resistance in C. coli by revealing a novel STR resistance gene possibly inherent to Campylobacter.

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2016-07-01
2019-10-16
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References

  1. Aarestrup F. M., Engberg J..( 2001;). Antimicrobial resistance of thermophilic Campylobacter. . Vet Res 32: 311–321. [CrossRef] [PubMed]
    [Google Scholar]
  2. Abril C., Brodard I., Perreten V..( 2010;). Two novel antibiotic resistance genes, tet(44) and ant(6)-Ib, are located within a transferable pathogenicity island in Campylobacter fetus subsp. fetus. . Antimicrob Agents Chemother 54: 3052–3055. [CrossRef] [PubMed]
    [Google Scholar]
  3. Aziz R. K., Bartels D., Best A. A., DeJongh M., Disz T., Edwards R. A., Formsma K., Gerdes S., Glass E. M. et al.( 2008;). The RAST Server: rapid annotations using subsystems technology. . BMC Genomics 9: 9–75. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bankevich A., Nurk S., Antipov D., Gurevich A. A., Dvorkin M., Kulikov A. S., Lesin V. M., Nikolenko S. I., Pham S. et al.( 2012;). SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. . J Comput Biol 19: 455–477. [CrossRef] [PubMed]
    [Google Scholar]
  5. Carter A. P., Clemons W. M., Brodersen D. E., Morgan-Warren R. J., Wimberly B. T., Ramakrishnan V..( 2000;). Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. . Nature 407: 340–348. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chen Y., Mukherjee S., Hoffmann M., Kotewicz M. L., Young S., Abbott J., Luo Y., Davidson M. K., Allard M. et al.( 2013;). Whole-genome sequencing of gentamicin-resistant Campylobacter coli isolated from U.S. retail meats reveals novel plasmid-mediated aminoglycoside resistance genes. . Antimicrob Agents Chemother 57: 5398–5405. [CrossRef] [PubMed]
    [Google Scholar]
  7. Davies J., Wright G. D..( 1997;). Bacterial resistance to aminoglycoside antibiotics. . Trends Microbiol 5: 234–240. [CrossRef] [PubMed]
    [Google Scholar]
  8. Finken M., Kirschner P., Meier A., Wrede A., Böttger E. C..( 1993;). Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot. . Mol Microbiol 9: 1239–1246.[PubMed] [CrossRef]
    [Google Scholar]
  9. Franklin K., Clarke A. J..( 2001;). Overexpression and characterization of the chromosomal aminoglycoside 2ʹ-N-acetyltransferase of Providencia stuartii. . Antimicrob Agents Chemother 45: 2238–2244. [CrossRef] [PubMed]
    [Google Scholar]
  10. Funatsu G., Wittmann H. G..( 1972;). Ribosomal proteins. 33. Location of amino-acid replacements in protein S12 isolated from Escherichia coli mutants resistant to streptomycin. . J Mol Biol 68: 547–550.[PubMed] [CrossRef]
    [Google Scholar]
  11. Giacomelli M., Salata C., Martini M., Montesissa C., Piccirillo A..( 2014;). Antimicrobial resistance of Campylobacter jejuni and Campylobacter coli from poultry in Italy. . Microb Drug Resist 20: 181–188. [CrossRef] [PubMed]
    [Google Scholar]
  12. Gibreel A., Sköld O., Taylor D. E..( 2004;). Characterization of plasmid-mediated aphA-3 kanamycin resistance in Campylobacter jejuni. . Microb Drug Resist 10: 98–105. [CrossRef] [PubMed]
    [Google Scholar]
  13. Guévremont E., Nadeau E., Sirois M., Quessy S..( 2006;). Antimicrobial susceptibilities of thermophilic Campylobacter from humans, swine, and chicken broilers. . Can J Vet Res 70: 81–86.[PubMed]
    [Google Scholar]
  14. Hanson R. M., Prilusky J., Renjian Z., Nakane T., Sussman J. L..( 2013;). JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. . Isr J Chem 53: 207–216.[CrossRef]
    [Google Scholar]
  15. Juntunen P., Heiska H., Olkkola S., Myllyniemi A. L., Hänninen M. L..( 2010;). Antimicrobial resistance in Campylobacter coli selected by tylosin treatment at a pig farm. . Vet Microbiol 146: 90–97. [CrossRef] [PubMed]
    [Google Scholar]
  16. Juntunen P., Olkkola S., Hänninen M. L..( 2011;). Longitudinal on-farm study of the development of antimicrobial resistance in Campylobacter coli from pigs before and after danofloxacin and tylosin treatments. . Vet Microbiol 150: 322–330. [CrossRef] [PubMed]
    [Google Scholar]
  17. Katoh K., Misawa K., Kuma K., Miyata T..( 2002;). MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. . Nucleic Acids Res 30: 3059–3066. [CrossRef] [PubMed]
    [Google Scholar]
  18. Kelley L. A., Sternberg M. J..( 2009;). Protein structure prediction on the Web: a case study using the Phyre server. . Nat Protoc 4: 363–371. [CrossRef] [PubMed]
    [Google Scholar]
  19. Kelley L. A., Mezulis S., Yates C. M., Wass M. N., Sternberg M. J..( 2015;). The Phyre2 web portal for protein modeling, prediction and analysis. . Nat Protoc 10: 845–858. [CrossRef] [PubMed]
    [Google Scholar]
  20. Kovanen S. M., Kivistö R. I., Rossi M., Schott T., Kärkkäinen U. M., Tuuminen T., Uksila J., Rautelin H., Hänninen M. L..( 2014;). Multilocus sequence typing (MLST) and whole-genome MLST of Campylobacter jejuni isolates from human infections in three districts during a seasonal peak in Finland. . J Clin Microbiol 52: 4147–4154. [CrossRef] [PubMed]
    [Google Scholar]
  21. Letunic I., Bork P..( 2011;). Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy. . Nucleic Acids Res 39: W475–478. [CrossRef] [PubMed]
    [Google Scholar]
  22. Llarena A. K., Huneau A., Hakkinen M., Hänninen M. L..( 2015;). Predominant Campylobacter jejuni sequence types persist in Finnish chicken production. . PLoS One 10: e0116585. [CrossRef] [PubMed]
    [Google Scholar]
  23. Llarena A. K., Skarp-de Haan C. P., Rossi M., Hänninen M. L..( 2015;). Characterization of the Campylobacter jejuni population in the barnacle geese reservoir. . Zoonoses Public Health 62: 209–221. [CrossRef] [PubMed]
    [Google Scholar]
  24. Magnet S., Blanchard J. S..( 2005;). Molecular insights into aminoglycoside action and resistance. . Chem Rev 105: 477–498. [CrossRef] [PubMed]
    [Google Scholar]
  25. Meier A., Sander P., Schaper K. J., Scholz M., Böttger E. C..( 1996;). Correlation of molecular resistance mechanisms and phenotypic resistance levels in streptomycin-resistant Mycobacterium tuberculosis. . Antimicrob Agents Chemother 40: 2452–2454.[PubMed]
    [Google Scholar]
  26. Miller J. F., Dower W. J., Tompkins L. S..( 1988;). High-voltage electroporation of bacteria: genetic transformation of Campylobacter jejuni with plasmid DNA. . Proc Natl Acad Sci U S A 85: 856–860.[PubMed] [CrossRef]
    [Google Scholar]
  27. Morar M., Bhullar K., Hughes D. W., Junop M., Wright G. D..( 2009;). Structure and mechanism of the lincosamide antibiotic adenylyltransferase LinB. . Structure 17: 1649–1659. [CrossRef] [PubMed]
    [Google Scholar]
  28. Nirdnoy W., Mason C. J., Guerry P..( 2005;). Mosaic structure of a multiple-drug-resistant, conjugative plasmid from Campylobacter jejuni. . Antimicrob Agents Chemother 49: 2454–2459. [CrossRef] [PubMed]
    [Google Scholar]
  29. O'Connor E. B., O'Sullivan O., Stanton C., Danielsen M., Simpson P. J., Callanan M. J., Ross R. P., Hill C..( 2007;). pEOC01: a plasmid from Pediococcus acidilactici which encodes an identical streptomycin resistance (aadE) gene to that found in Campylobacter jejuni. . Plasmid 58: 115–126. [CrossRef] [PubMed]
    [Google Scholar]
  30. Olkkola S., Juntunen P., Heiska H., Hyytiäinen H., Hänninen M. L..( 2010;). Mutations in the rpsL gene are involved in streptomycin resistance in Campylobacter coli. . Microb Drug Resist 16: 105–110. [CrossRef] [PubMed]
    [Google Scholar]
  31. Ounissi H., Derlot E., Carlier C., Courvalin P..( 1990;). Gene homogeneity for aminoglycoside-modifying enzymes in gram-positive cocci. . Antimicrob Agents Chemother 34: 2164–2168. [CrossRef] [PubMed]
    [Google Scholar]
  32. Pezzotti G., Serafin A., Luzzi I., Mioni R., Milan M., Perin R..( 2003;). Occurrence and resistance to antibiotics of Campylobacter jejuni and Campylobacter coli in animals and meat in northeastern Italy. . Int J Food Microbiol 82: 281–287.[PubMed] [CrossRef]
    [Google Scholar]
  33. Qin S., Wang Y., Zhang Q., Chen X., Shen Z., Deng F., Wu C., Shen J..( 2012;). Identification of a novel genomic island conferring resistance to multiple aminoglycoside antibiotics in Campylobacter coli. . Antimicrob Agents Chemother 56: 5332–5339. [CrossRef] [PubMed]
    [Google Scholar]
  34. Qin S. S., Wu C. M., Wang Y., Jeon B., Shen Z. Q., Wang Y., Zhang Q., Shen J. Z., Wang Y..( 2011;). Antimicrobial resistance in Campylobacter coli isolated from pigs in two provinces of China. . Int J Food Microbiol 146: 94–98. [CrossRef] [PubMed]
    [Google Scholar]
  35. Ramirez M. S., Tolmasky M. E..( 2010;). Aminoglycoside modifying enzymes. . Drug Resist Updat 13: 151–171. [CrossRef] [PubMed]
    [Google Scholar]
  36. Rasko D. A., Myers G. S., Ravel J..( 2005;). Visualization of comparative genomic analyses by BLAST score ratio. . BMC Bioinformatics 6: 2. [CrossRef] [PubMed]
    [Google Scholar]
  37. Rzhetsky A., Nei M..( 1992;). Statistical properties of the ordinary least-squares, generalized least-squares, and minimum-evolution methods of phylogenetic inference. . J Mol Evol 35: 367–375.[PubMed] [CrossRef]
    [Google Scholar]
  38. Shaw K. J., Rather P. N., Hare R. S., Miller G. H..( 1993;). Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. . Microbiol Rev 57: 138–163.[PubMed]
    [Google Scholar]
  39. Sheppard S. K., Didelot X., Jolley K. A., Darling A. E., Pascoe B., Meric G., Kelly D. J., Cody A., Colles F. M. et al.( 2013;). Progressive genome-wide introgression in agricultural Campylobacter coli. . Mol Ecol 22: 1051–1064. [CrossRef] [PubMed]
    [Google Scholar]
  40. Sheppard S. K., Cheng L., Méric G., de Haan C. P., Llarena A. K., Marttinen P., Vidal A., Ridley A., Clifton-Hadley F. et al.( 2014;). Cryptic ecology among host generalist Campylobacter jejuni in domestic animals. . Mol Ecol 23: 2442–2451. [CrossRef] [PubMed]
    [Google Scholar]
  41. Smith C. A., Baker E. N..( 2002;). Aminoglycoside antibiotic resistance by enzymatic deactivation. . Curr Drug Targets Infect Disord 2: 143–160. [CrossRef] [PubMed]
    [Google Scholar]
  42. Stabler R. A., Larsson J. T., Al-Jaberi S., Nielsen E. M., Kay E., Tam C. C., Higgins C. D., Rodrigues L. C., Richardson J. F. et al.( 2013;). Characterization of water and wildlife strains as a subgroup of Campylobacter jejuni using DNA microarrays. . Environ Microbiol 15: 2371–2383. [CrossRef] [PubMed]
    [Google Scholar]
  43. Sullivan M. J., Petty N. K., Beatson S. A..( 2011;). Easyfig: a genome comparison visualizer. . Bioinformatics 27: 1009–1010. [CrossRef] [PubMed]
    [Google Scholar]
  44. Taboada E. N., Acedillo R. R., Carrillo C. D., Findlay W. A., Medeiros D. T., Mykytczuk O. L., Roberts M. J., Valencia C. A., Farber J. M. et al.( 2004;). Large-scale comparative genomics meta-analysis of Campylobacter jejuni isolates reveals low level of genome plasticity. . J Clin Microbiol 42: 4566–4576. [CrossRef] [PubMed]
    [Google Scholar]
  45. Tamura K., Peterson D., Peterson N., Stecher G., Nei M., Kumar S..( 2011;). MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. . Mol Biol Evol 28: 2731–2739. [CrossRef] [PubMed]
    [Google Scholar]
  46. Torii N., Nozaki T., Masutani M., Nakagama H., Sugiyama T., Saito D., Asaka M., Sugimura T., Miki K..( 2003;). Spontaneous mutations in the Helicobacter pylori rpsL gene. . Mutat Res 535: 141–145.[PubMed] [CrossRef]
    [Google Scholar]
  47. Torralbo A., Borge C., García-Bocanegra I., Méric G., Perea A., Carbonero A..( 2015;). Higher resistance of Campylobacter coli compared to Campylobacter jejuni at chicken slaughterhouse. . Comp Immunol Microbiol Infect Dis 39: 47–52. [CrossRef] [PubMed]
    [Google Scholar]
  48. Vakulenko S. B., Mobashery S..( 2003;). Versatility of aminoglycosides and prospects for their future. . Clin Microbiol Rev 16: 430–450.[PubMed] [CrossRef]
    [Google Scholar]
  49. van Vliet A. H., Wooldridge K. G., Ketley J. M..( 1998;). Iron-responsive gene regulation in a Campylobacter jejuni fur mutant. . J Bacteriol 180: 5291–5298.[PubMed]
    [Google Scholar]
  50. Wang Y., Huang W. M., Taylor D. E..( 1993;). Cloning and nucleotide sequence of the Campylobacter jejuni gyrA gene and characterization of quinolone resistance mutations. . Antimicrob Agents Chemother 37: 457–463. [CrossRef] [PubMed]
    [Google Scholar]
  51. Zhang J., Halkilahti J., Hänninen M. L., Rossi M..( 2015;). Refinement of whole-genome multilocus sequence typing analysis by addressing gene paralogy. . J Clin Microbiol 53: 1765–1767. [CrossRef] [PubMed]
    [Google Scholar]
  52. Zhang M., Liu X., Xu X., Gu Y., Tao X., Yang X., Yan G., Zhang J..( 2014;). Molecular subtyping and antimicrobial susceptibilities of Campylobacter coli isolates from diarrheal patients and food-producing animals in China. . Foodborne Pathog Dis 11: 610–619. [CrossRef] [PubMed]
    [Google Scholar]
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