Genomic surveillance links livestock production with the emergence and spread of multi-drug resistant non-typhoidal Salmonella in Mexico

  • Enrique Jesús Delgado-SuárezEmail author
  • Rocío Ortíz-López
  • Wondwossen A. Gebreyes
  • Marc W. Allard
  • Francisco Barona-Gómez
  • María Salud Rubio-Lozano


Multi-drug resistant (MDR) non-typhoidal Salmonella (NTS) is increasingly common worldwide. While food animals are thought to contribute to the growing antimicrobial resistance (AMR) problem, limited data is documenting this relationship, especially in low and middle-income countries (LMIC). Herein, we aimed to assess the role of non-clinical NTS of bovine origin as reservoirs of AMR genes of human clinical significance. We evaluated the phenotypic and genotypic AMR profiles in a set of 44 bovine-associated NTS. For comparative purposes, we also included genotypic AMR data of additional isolates from Mexico (n = 1,067) that are publicly available. The most frequent AMR phenotypes in our isolates involved tetracycline (40/44), trimethoprim-sulfamethoxazole (26/44), chloramphenicol (19/44), ampicillin (18/44), streptomycin (16/44), and carbenicillin (13/44), while nearly 70% of the strains were MDR. These phenotypes were correlated with a widespread distribution of AMR genes (i.e. tetA, aadA, dfrA12, dfrA17, sul1, sul2, bla-TEM-1, blaCARB-2) against multiple antibiotic classes, with some of them contributed by plasmids and/or class-1 integrons. We observed different AMR genotypes for betalactams and tetracycline resistance, providing evidence of convergent evolution and adaptive AMR. The probability of MDR genotype occurrence was higher in meat-associated isolates than in those from other sources (odds ratio 11.2, 95% confidence interval 4.5–27.9, P < 0.0001). The study shows that beef cattle are a significant source of MDR NTS in Mexico, highlighting the role of animal production on the emergence and spread of MDR Salmonella in LMIC.


antimicrobial resistance Salmonella genomics beef production 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

12275_2019_8421_MOESM1_ESM.pdf (1.9 mb)
Supplementary material, approximately 1.94 MB.
12275_2019_8421_MOESM2_ESM.xlsx (13 kb)
Supplementary material, approximately 12.5 KB.
12275_2019_8421_MOESM3_ESM.xlsx (96 kb)
Supplementary data Table S2. Database of isolates from Mexico with AMR genotypes that were publicly available at NCBI as of July 24 2018
12275_2019_8421_MOESM4_ESM.xlsx (20 kb)
Supplementary data Table S3. Summary of genome assembly and annotation results


  1. An, R., Alshalchi, S., Breimhurst, P., Munoz-Aguayo, J., Flores-Figueroa, C., and Vidovic, S. 2017. Strong influence of livestock environments on the emergence and dissemination of distinct multidrug-resistant phenotypes among the population of non-typhoidal Salmonella. PLoS One 12, e0179005.CrossRefGoogle Scholar
  2. Antunes, P., Machado, J., and Peixe, L. 2006. Characterization of antimicrobial resistance and class 1 and 2 integrons in Salmonella enterica isolates from different sources in Portugal. J. Antimicrob. Chemother. 58, 297–304.CrossRefGoogle Scholar
  3. Baron, S., Hadjadj, L., Rolain, J.M., and Olaitan, A.O. 2016. Molecular mechanisms of polymyxin resistance: Knowns and unknowns. Int. J. Antimicrob. Agents 48, 583–591.CrossRefGoogle Scholar
  4. Bauer, A.W., Kirby, W.M., Sherris, J.C., and Turck, M. 1966. Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin. Pathol. 45, 493–496.CrossRefGoogle Scholar
  5. Brichta-Harhay, D.M., Arthur, T.M., Bosilevac, J.M., Kalchayanand, N., Shackelford, S.D., Wheeler, T.L., and Koohmaraie, M. 2011. Diversity of multidrug-resistant Salmonella enterica strains associated with cattle at harvest in the United States. Appl. Environ. Microbiol. 77, 1783–1796.CrossRefGoogle Scholar
  6. Carattoli, A., Zankari, E., García-Fernández, A., Larsen, M.V., Lund, O., Villa, L., Aarestrup, F.M., and Hasman, H. 2014. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob. Agents Chemother. 58, 3895–3903.CrossRefGoogle Scholar
  7. Castresana, J. 2000. Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol. Biol. Evol. 17, 540–552.CrossRefGoogle Scholar
  8. Chang, H.H., Cohen, T., Grad, Y.H., Hanage, W.P., O’Brien, T.F., and Lipsitch, M. 2015. Origin and proliferation of multiple-drug resistance in bacterial pathogens. Microbiol. Mol. Biol. Rev. 79, 101–116.CrossRefGoogle Scholar
  9. CLSI. 2012. Clinical and laboratory standards institute. Performance standards for antimicrobial disk susceptibility tests; Approved standard-Eleventh edition. CLSI document M02-A11. CLSI, Wayne, PA, USA.Google Scholar
  10. Delgado-Suárez, E.J., Selem-Mojica, N., Ortiz-Lopez, R., Gebreyes, W.A., Allard, M.W., Barona-Gomez, F., and Rubio-Lozano, M.S. 2018. Whole genome sequencing reveals widespread distribution of typhoidal toxin genes and VirB/D4 plasmids in bovineassociated nontyphoidal Salmonella. Sci. Rep. 8, 9864.CrossRefGoogle Scholar
  11. Dhanani, A.S., Block, G., Dewar, K., Forgetta, V., Topp, E., Beiko, R.G., and Diarra, M.S. 2015. Genomic comparison of non-typhoidal Salmonella enterica serovars Typhimurium, Enteritidis, Heidelberg, Hadar and Kentucky isolates from broiler chickens. PLoS One 10, e0128773.CrossRefGoogle Scholar
  12. Edgar, R. and Bibi, E. 1997. MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition. J. Bacteriol. 179, 2274–2280.CrossRefGoogle Scholar
  13. Gouy, M., Guindon, S., and Gascuel, O. 2010. SeaView version 4: A multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol. Biol. Evol. 27, 221–224.CrossRefGoogle Scholar
  14. Hoffmann, S., Batz, M.B., and Morris, J.G.Jr. 2012. Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens. J. Food Prot. 75, 1292–1302.CrossRefGoogle Scholar
  15. Jia, B., Raphenya, A.R., Alcock, B., Waglechner, N., Guo, P., Tsang, K.K., Lago, B.A., Dave, B.M., Pereira, S., Sharma, A.N., et al. 2017. CARD 2017: Expansion and model-centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res. 45, D566–D573.CrossRefGoogle Scholar
  16. Junod, T., López-Martín, J., and Gädicke, P. 2013. Antimicrobial susceptibility of animal and food isolates of Salmonella enterica. Rev. Med. Chile 141, 298–304.CrossRefGoogle Scholar
  17. Kalambhe, D.G., Zade, N.N., Chaudhari, S.P., Shinde, S.V., Khan, W., and Patil, A.R. 2016. Isolation, antibiogram and pathogenicity of Salmonella spp. recovered from slaughtered food animals in Nagpur region of Central India. Vet. World 9, 176–181.CrossRefGoogle Scholar
  18. Karczmarczyk, M., Martins, M., McCusker, M., Mattar, S., Amaral, L., Leonard, N., Aarestrup, F.M., and Fanning, S. 2010. Characterization of antimicrobial resistance in Salmonella enterica food and animal isolates from Colombia: identification of a qnrB19- mediated quinolone resistance marker in two novel serovars. FEMS Microbiol. Lett. 313, 10–19.CrossRefGoogle Scholar
  19. Lin, D., Chen, K., Wai-Chi Chan, E., and Chen, S. 2015. Increasing prevalence of ciprofloxacin-resistant food-borne Salmonella strains harboring multiple PMQR elements but not target gene mutations. Sci. Rep. 5, 14754.CrossRefGoogle Scholar
  20. Lujan, S.A., Guogas, L.M., Ragonese, H., Matson, S.W., and Redinbo, M.R. 2007. Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Proc. Natl. Acad. Sci. USA 104, 12282–12287.CrossRefGoogle Scholar
  21. McEwen, S.A. and Fedorka-Cray, P.J. 2002. Antimicrobial use and resistance in animals. Clin. Infect. Dis. 34 (Suppl 3), S93–S106.CrossRefGoogle Scholar
  22. Meng, H., Zhang, Z., Chen, M., Su, Y., Li, L., Miyoshi, S., Yan, H., and Shi, L. 2011. Characterization and horizontal transfer of class 1 integrons in Salmonella strains isolated from food products of animal origin. Int. J. Food Microbiol. 149, 274–277.CrossRefGoogle Scholar
  23. Mir, R.A., Weppelmann, T.A., Johnson, J.A., Archer, D., Morris, J.G.Jr., and Jeong, K.C. 2016. Identification and characterization of cefotaxime resistant bacteria in beef cattle. PLoS One 11, e0163279.CrossRefGoogle Scholar
  24. OECD. 2016. Antimicrobial resistance. Policy insights. Available online: (accessed on 5 October 2018).
  25. Perez-Montaño, J.A., González-Aguilar, D., Barba, J., Pacheco-Gallardo, C., Campos-Bravo, C.A., García, S., Heredia, N.L., and Cabrera-Díaz, E. 2012. Frequency and antimicrobial resistance of Salmonella serotypes on beef carcasses at small abattoirs in Jalisco State, Mexico. J. Food Prot. 75, 867–873.CrossRefGoogle Scholar
  26. Poole, K. 2012. Bacterial stress responses as determinants of antimicrobial resistance. J. Antimicrob. Chemother. 67, 2069–2089.CrossRefGoogle Scholar
  27. Qiu, H., Gong, J., Butaye, P., Lu, G., Huang, K., Zhu, G., Zhang, J., Hathcock, T., Cheng, D., and Wang, C. 2018. CRISPR/Cas9/ sgRNA-mediated targeted gene modification confirms the causeeffect relationship between gyrA mutation and quinolone resistance in Escherichia coli. FEMS Microbiol. Lett. 365, fny127.CrossRefGoogle Scholar
  28. Quesada, A., Porrero, M.C., Tellez, S., Palomo, G., Garcia, M., and Dominguez, L. 2015. Polymorphism of genes encoding PmrAB in colistin-resistant strains of Escherichia coli and Salmonella enterica isolated from poultry and swine. J. Antimicrob. Chemother. 70, 71–74.CrossRefGoogle Scholar
  29. Quesada, A., Reginatto, G.A., Ruiz Español, A., Colantonio, L.D., and Burrone, M.S. 2016. Antimicrobial resistance of Salmonella spp. isolated animal food for human consumption. Rev. Perú. Med. Exp. Salud Pública 33, 32.CrossRefGoogle Scholar
  30. Ronquist, F., Teslenko, M., van der Mark, P., Ayres, D.L., Darling, A., Hohna, S., Larget, B., Liu, L., Suchard, M.A., and Huelsenbeck, J.P. 2012. MrBayes 3.2: Efficient Bayesian phylogenetic inference and model choice across a large model space. Syst. Biol. 61, 539–542.CrossRefGoogle Scholar
  31. SAGARPA. 2018. Productos químico-farmacéuticos vigentes 2017. Available online: (accessed on 5 October 2018).
  32. Schmidt, J.W., Agga, G.E., Bosilevac, J.M., Brichta-Harhay, D.M., Shackelford, S.D., Wang, R., Wheeler, T.L., and Arthur, T.M. 2015. Occurrence of antimicrobial-resistant Escherichia coli and Salmonella enterica in the beef cattle production and processing continuum. Appl. Environ. Microbiol. 81, 713–725.CrossRefGoogle Scholar
  33. Sibhat, B., Molla Zewde, B., Zerihun, A., Muckle, A., Cole, L., Boerlin, P., Wilkie, E., Perets, A., Mistry, K., and Gebreyes, W.A. 2011. Salmonella serovars and antimicrobial resistance profiles in beef cattle, slaughterhouse personnel and slaughterhouse environment in Ethiopia. Zoonoses Public Health 58, 102–109.CrossRefGoogle Scholar
  34. Sievers, F., Wilm, A., Dineen, D., Gibson, T.J., Karplus, K., Li, W., Lopez, R., McWilliam, H., Remmert, M., Soding, J., et al. 2011. Fast, scalable generation of high-quality protein multiple sequence alignments using clustal omega. Mol. Syst. Biol. 7, 539.CrossRefGoogle Scholar
  35. Strahilevitz, J., Jacoby, G.A., Hooper, D.C., and Robicsek, A. 2009. Plasmid-mediated quinolone resistance: A multifaceted threat. Clin. Microbiol. Rev. 22, 664–689.CrossRefGoogle Scholar
  36. Swick, M.C., Morgan-Linnell, S.K., Carlson, K.M., and Zechiedrich, L. 2011. Expression of multidrug efflux pump genes acrAB-tolC, mdfA, and norE in Escherichia coli clinical isolates as a function of fluoroquinolone and multidrug resistance. Antimicrob. Agents Chemother. 55, 921–924.CrossRefGoogle Scholar
  37. Talbot, E.A., Gagnon, E.R., and Greenblatt, J. 2006. Common ground for the control of multidrug-resistant Salmonella in ground beef. Clin. Infect. Dis. 42, 1455–1462.CrossRefGoogle Scholar
  38. Van, T.T., Nguyen, H.N., Smooker, P.M., and Coloe, P.J. 2012. The antibiotic resistance characteristics of non-typhoidal Salmonella enterica isolated from food-producing animals, retail meat and humans in South East Asia. Int. J. Food Microbiol. 154, 98–106.CrossRefGoogle Scholar
  39. Varela-Guerrero, J.A., Talavera-Rojas, M., Gutierrez-Castillo Adel, C., Reyes-Rodriguez, N.E., and Vazquez-Guadarrama, J. 2013. Phenotypic-genotypic resistance in Salmonella spp. isolated from cattle carcasses from the north central zone of the State of Mexico. Trop. Anim. Health Prod. 45, 995–1000.CrossRefGoogle Scholar
  40. WHO. 2015. WHO estimates of the global burden of foodborne diseases. Foodborne disease burden epidemiology reference group 2007–2015. Available online: (accessed on 5 October 2018).
  41. WHO. 2017. WHO list of critically important antimicrobials for human medicine 5th revision. Available online: (accessed on 5 October 2018).
  42. Williams, J.J. and Hergenrother, P.J. 2008. Exposing plasmids as the Achilles’ heel of drug-resistant bacteria. Curr. Opin. Chem. Biol. 12, 389–399.CrossRefGoogle Scholar
  43. Zankari, E., Allesoe, R., Joensen, K.G., Cavaco, L.M., Lund, O., and Aarestrup, F.M. 2017. PointFinder: a novel web tool for WGSbased detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens. J. Antimicrob. Chemother. 72, 2764–2768.CrossRefGoogle Scholar
  44. Zankari, E., Hasman, H., Cosentino, S., Vestergaard, M., Rasmussen, S., Lund, O., Aarestrup, F.M., and Larsen, M.V. 2012. Identification of acquired antimicrobial resistance genes. J. Antimicrob. Chemother. 67, 2640–2644.CrossRefGoogle Scholar
  45. Zhang, S., Yin, Y., Jones, M.B., Zhang, Z., Deatherage Kaiser, B.L., Dinsmore, B.A., Fitzgerald, C., Fields, P.I., and Deng, X. 2015. Salmonella serotype determination utilizing high-throughput genome sequencing data. J. Clin. Microbiol. 53, 1685–1692.CrossRefGoogle Scholar

Copyright information

© The Microbiological Society of Korea and Springer Nature B.V. 2019

Authors and Affiliations

  • Enrique Jesús Delgado-Suárez
    • 1
    Email author
  • Rocío Ortíz-López
    • 2
  • Wondwossen A. Gebreyes
    • 3
  • Marc W. Allard
    • 4
  • Francisco Barona-Gómez
    • 5
  • María Salud Rubio-Lozano
    • 1
  1. 1.Facultad de Medicina Veterinaria y ZootecniaUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  2. 2.Tecnológico de MonterreySchool of Medicine and Health SciencesMonterreyMexico
  3. 3.College of Veterinary MedicineThe Ohio State UniversityColumbusUSA
  4. 4.Office of Regulatory Science, Center for Food Safety and Applied NutritionU. S. Food and Drug AdministrationCollege ParkUSA
  5. 5.Evolution of Metabolic Diversity LaboratoryUnidad de Genómica Avanzada (Langebio)Cinvestav-IPN, Irapuato, GuanajuatoMexico

Personalised recommendations