Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer

Frontiers in Microbiology

Volumn 7, Issue FEB, 2016, Pages

  Von Wintersdorff, Christian J H ^a   Penders, John ^a   Van Niekerk, Julius M ^a   Mills, Nathan D ^a   Majumder, Snehali ^a   Van Alphen, Lieke B ^a   Savelkoul, Paul H M ^a,b   Wolffs, Petra F G ^a  

^a MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Antibiotic resistance; Conjugation; Gene transfer agents; GTA; Lateral gene transfer; Resistome; Transduction; Transformation

Indexed keywords

ANTIBIOTIC RESISTANCE; CONJUGATION; ECOSYSTEM; HORIZONTAL GENE TRANSFER; MOBILIZATION; THINKING;

EID: 84962157709     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2016.00173     Document Type: Review

References (146)

1. Alexander, H. E., Hahn, E., and Leidy, G. (1956). On the specificity of the desoxyribonucleic acid which induces streptomycin resistance in Hemophilus. J. Exp. Med. 104, 305-320. doi: 10.1084/jem.104.3.305
2. Alexander, H. E., and Leidy, G. (1953). Induction of streptomycin resistance in sensitive Hemophilus influenzae by extracts containing desoxyribonucleic acid from resistant Hemophilus influenzae. J. Exp. Med. 97, 17-31. doi: 10.1084/jem.97.1.17
3. Allen, H. K., Moe, L. A., Rodbumrer, J., Gaarder, A., and Handelsman, J. (2009). Functional metagenomics reveals diverse β-lactamases in a remote Alaskan soil. ISME J. 3, 243-251. doi: 10.1038/ismej.2008.86
4. Aminov, R. I. (2009). The role of antibiotics and antibiotic resistance in nature. Environ. Microbiol. 11, 2970-2988. doi: 10.1111/j.1462-2920.2009.01972.x
5. Arcilla, M. S., van Hattem, J. M., Matamoros, S., Melles, D. C., Penders, J., de Jong, M. D., et al. (2015). Dissemination of the mcr-1 colistin resistance gene. Lancet Infect. Dis. 16, 147-149. doi: 10.1016/S1473-3099(15)00541-1
6. Balsalobre, L., Ferrandiz, M. J., Linares, J., Tubau, F., and de la Campa, A. G. (2003). Viridans group streptococci are donors in horizontal transfer of topoisomerase IV genes to Streptococcus pneumoniae. Antimicrob. Agents Chemother. 47, 2072-2081. doi: 10.1128/AAC.47.7.2072-2081.2003
7. Barlow, M., and Hall, B. G. (2002). Phylogenetic analysis shows that the OXA β-lactamase genes have been on plasmids for millions of years. J. Mol. Evol. 55, 314-321. doi: 10.1007/s00239-002-2328-y
8. Bhullar, K., Waglechner, N., Pawlowski, A., Koteva, K., Banks, E. D., Johnston, M. D., et al. (2012). Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS ONE 7:e34953. doi: 10.1371/journal.pone.0034953
9. Biers, E. J., Wang, K., Pennington, C., Belas, R., Chen, F., and Moran, M. A. (2008). Occurrence and expression of gene transfer agent genes in marine bacterioplankton. Appl. Environ. Microbiol. 74, 2933-2939. doi: 10.1128/AEM.02129-07
10. Billard-Pomares, T., Fouteau, S., Jacquet, M. E., Roche, D., Barbe, V., Castellanos, M., et al. (2014). Characterization of a P1-like bacteriophage carrying an SHV-2 extended-spectrum β-lactamase from an Escherichia coli strain. Antimicrob. Agents Chemother. 58, 6550-6557. doi: 10.1128/AAC.03183-14
11. Bowler, L. D., Zhang, Q. Y., Riou, J. Y., and Spratt, B. G. (1994). Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation. J. Bacteriol. 176, 333-337.
12. Brimacombe, C. A., Ding, H., and Beatty, J. T. (2014). Rhodobacter capsulatus DprA is essential for RecA-mediated gene transfer agent (RcGTA) recipient capability regulated by quorum-sensing and the CtrA response regulator. Mol. Microbiol. 92, 1260-1278. doi: 10.1111/mmi.12628
13. Brimacombe, C. A., Ding, H., Johnson, J. A., and Beatty, J. T. (2015). Homologues of genetic transformation DNA import genes are required for Rhodobacter capsulatus gene transfer agent recipient capability regulated by the response regulator CtrA. J. Bacteriol. 197, 2653-2663. doi: 10.1128/JB.00332-15
14. Brown-Jaque, M., Calero-Caceres, W., and Muniesa, M. (2015). Transfer of antibiotic-resistance genes via phage-related mobile elements. Plasmid 79, 1-7. doi: 10.1016/j.plasmid.2015.01.001
15. Cabello, F. C. (2006). Heavy use of prophylactic antibiotics in aquaculture: a growing problem for human and animal health and for the environment. Environ. Microbiol. 8, 1137-1144. doi: 10.1111/j.1462-2920.2006.01054.x
16. Calero-Caceres, W., Melgarejo, A., Colomer-Lluch, M., Stoll, C., Lucena, F., Jofre, J., et al. (2014). Sludge as a potential important source of antibiotic resistance genes in both the bacterial and bacteriophage fractions. Environ. Sci. Technol. 48, 7602-7611. doi: 10.1021/es501851s
17. Canton, R., and Coque, T. M. (2006). The CTX-M β-lactamase pandemic. Curr. Opin. Microbiol. 9, 466-475. doi: 10.1016/j.mib.2006.08.011
18. Canton, R., Gonzalez-Alba, J. M., and Galan, J. C. (2012). CTX-M enzymes: origin and diffusion. Front. Microbiol. 3:110. doi: 10.3389/fmicb.2012.00110
19. Carattoli, A. (2013). Plasmids and the spread of resistance. Int. J. Med. Microbiol. 303, 298-304. doi: 10.1016/j.ijmm.2013.02.001
20. Card, R. M., Warburton, P. J., MacLaren, N., Mullany, P., Allan, E., and Anjum, M. F. (2014). Application of microarray and functional-based screening methods for the detection of antimicrobial resistance genes in the microbiomes of healthy humans. PLoS ONE 9:e86428. doi: 10.1371/journal.pone.0086428
21. Chancey, S. T., Agrawal, S., Schroeder, M. R., Farley, M. M., Tettelin, H., and Stephens, D. S. (2015). Composite mobile genetic elements disseminating macrolide resistance in Streptococcus pneumoniae. Front. Microbiol. 6:26. doi: 10.3389/fmicb.2015.00026
22. Charpentier, X., Kay, E., Schneider, D., and Shuman, H. A. (2011). Antibiotics and UV radiation induce competence for natural transformation in Legionella pneumophila. J. Bacteriol. 193, 1114-1121. doi: 10.1128/JB.01146-10
23. Charpentier, X., Polard, P., and Claverys, J. P. (2012). Induction of competence for genetic transformation by antibiotics: convergent evolution of stress responses in distant bacterial species lacking SOS? Curr. Opin. Microbiol. 15, 570-576. doi: 10.1016/j.mib.2012.08.001
24. Cheng, G., Hu, Y., Yin, Y., Yang, X., Xiang, C., Wang, B., et al. (2012). Functional screening of antibiotic resistance genes from human gut microbiota reveals a novel gene fusion. FEMS Microbiol. Lett. 336, 11-16. doi: 10.1111/j.1574-6968.2012.02647.x
25. Clemente, J. C., Pehrsson, E. C., Blaser, M. J., Sandhu, K., Gao, Z., Wang, B., et al. (2015). The microbiome of uncontacted Amerindians. Sci. Adv. 1:e1500183. doi: 10.1126/sciadv.1500183
26. Colomer-Lluch, M., Calero-Caceres, W., Jebri, S., Hmaied, F., Muniesa, M., and Jofre, J. (2014a). Antibiotic resistance genes in bacterial and bacteriophage fractions of Tunisian and Spanish wastewaters as markers to compare the antibiotic resistance patterns in each population. Environ. Int. 73, 167-175. doi: 10.1016/j.envint.2014.07.003
27. Colomer-Lluch, M., Imamovic, L., Jofre, J., and Muniesa, M. (2011b). Bacteriophages carrying antibiotic resistance genes in fecal waste from cattle, pigs, and poultry. Antimicrob. Agents Chemother. 55, 4908-4911. doi: 10.1128/AAC.00535-11
28. Colomer-Lluch, M., Jofre, J., and Muniesa, M. (2011a). Antibiotic resistance genes in the bacteriophage DNA fraction of environmental samples. PLoS ONE 6:e17549. doi: 10.1371/journal.pone.0017549
29. Colomer-Lluch, M., Jofre, J., and Muniesa, M. (2014b). Quinolone resistance genes (qnrA and qnrS) in bacteriophage particles from wastewater samples and the effect of inducing agents on packaged antibiotic resistance genes. J. Antimicrob. Chemother. 69, 1265-1274. doi: 10.1093/jac/dkt528
30. Datta, N., and Hughes, V. M. (1983). Plasmids of the same Inc groups in Enterobacteria before and after the medical use of antibiotics. Nature. 306, 616-617. doi: 10.1038/306616a0
31. Davies, J. (2006). Are antibiotics naturally antibiotics? J. Ind. Microbiol. Biotechnol. 33, 496-499. doi: 10.1007/s10295-006-0112-5
32. Davison, J. (1999). Genetic exchange between bacteria in the environment. Plasmid 42, 73-91. doi: 10.1006/plas.1999.1421
33. D'Costa, V. M., King, C. E., Kalan, L., Morar, M., Sung, W. W., Schwarz, C., et al. (2011). Antibiotic resistance is ancient. Nature 477, 457-461. doi: 10.1038/nature10388
34. D'Costa, V. M., McGrann, K. M., Hughes, D. W., and Wright, G. D. (2006). Sampling the antibiotic resistome. Science 311, 374-377. doi: 10.1126/science.1120800
35. Domingues, S., Harms, K., Fricke, W. F., Johnsen, P. J., da Silva, G. J., and Nielsen, K. M. (2012). Natural transformation facilitates transfer of transposons, integrons and gene cassettes between bacterial species. PLoS Pathog. 8:e1002837. doi: 10.1371/journal.ppat.1002837
36. Donato, J. J., Moe, L. A., Converse, B. J., Smart, K. D., Berklein, F. C., McManus, P. S., et al. (2010). Metagenomic analysis of apple orchard soil reveals antibiotic resistance genes encoding predicted bifunctional proteins. Appl. Environ. Microbiol. 76, 4396-4401. doi: 10.1128/AEM.01763-09
37. Dowson, C. G., Hutchison, A., Woodford, N., Johnson, A. P., George, R. C., and Spratt, B. G. (1990). Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae. Proc. Natl. Acad. Sci. U.S.A. 87, 5858-5862. doi: 10.1073/pnas.87.15.5858
38. Economou, V., and Gousia, P. (2015). Agriculture and food animals as a source of antimicrobial-resistant bacteria. Infect. Drug Resist. 8, 49-61. doi: 10.2147/IDR.S55778
39. Ferrandiz, M. J., Fenoll, A., Linares, J., and De La Campa, A. G. (2000). Horizontal transfer of parC and gyrA in fluoroquinolone-resistant clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 44, 840-847. doi: 10.1128/AAC.44.4.840-847.2000
40. Fick, J., Soderstrom, H., Lindberg, R. H., Phan, C., Tysklind, M., and Larsson, D. G. (2009). Contamination of surface, ground, and drinking water from pharmaceutical production. Environ. Toxicol. Chem. 28, 2522-2527. doi: 10.1897/09-073.1
41. Fogg, P. C., Westbye, A. B., and Beatty, J. T. (2012). One for all or all for one: heterogeneous expression and host cell lysis are key to gene transfer agent activity in Rhodobacter capsulatus. PLoS ONE 7:e43772. doi: 10.1371/journal.pone.0043772
42. Forsberg, K. J., Reyes, A., Wang, B., Selleck, E. M., Sommer, M. O., and Dantas, G. (2012). The shared antibiotic resistome of soil bacteria and human pathogens. Science 337, 1107-1111. doi: 10.1126/science.1220761
43. Fouhy, F., Ogilvie, L. A., Jones, B. V., Ross, R. P., Ryan, A. C., Dempsey, E. M., et al. (2014). Identification of aminoglycoside and β-lactam resistance genes from within an infant gut functional metagenomic library. PLoS ONE 9:e108016. doi: 10.1371/journal.pone.0108016
44. Gibson, M. K., Forsberg, K. J., and Dantas, G. (2015). Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology. ISME J. 9, 207-216. doi: 10.1038/ismej.2014.106
45. Gonzalez, I., Georgiou, M., Alcaide, F., Balas, D., Linares, J., and de la Campa, A. G. (1998). Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci. Antimicrob. Agents Chemother. 42, 2792-2798.
46. Graham, D. W., Olivares-Rieumont, S., Knapp, C. W., Lima, L., Werner, D., and Bowen, E. (2011). Antibiotic resistance gene abundances associated with waste discharges to the Almendares River near Havana, Cuba. Environ. Sci. Technol. 45, 418-424. doi: 10.1021/es102473z
47. Griffith, F. (1928). The significance of pneumococcal types. J. Hyg. (Lond.) 27, 113-159. doi: 10.1017/S0022172400031879
48. Guglielmini, J., de la Cruz, F., and Rocha, E. P. (2013). Evolution of conjugation and type IV secretion systems. Mol. Biol. Evol. 30, 315-331. doi: 10.1093/molbev/mss221
49. Hakenbeck, R. (1998). Mosaic genes and their role in penicillin-resistant Streptococcus pneumoniae. Electrophoresis 19, 597-601. doi: 10.1002/elps.1150190423
50. Hall, B. G., and Barlow, M. (2004). Evolution of the serine β-lactamases: past, present and future. Drug Resist. Updat. 7, 111-123. doi: 10.1016/j.drup.2004.02.003
51. Hampson, D. J., and Ahmed, N. (2009). Spirochaetes as intestinal pathogens: lessons from a Brachyspira genome. Gut Pathog. 1:10. doi: 10.1186/1757-4749-1-10
52. Harford, N., and Mergeay, M. (1973). Interspecific transformation of rifampicin resistance in the genus Bacillus. Mol. Gen. Genet. 120, 151-155. doi: 10.1007/BF00267243
53. Hartmann, A., Locatelli, A., Amoureux, L., Depret, G., Jolivet, C., Gueneau, E., et al. (2012). Occurrence of CTX-M Producing Escherichia coli in Soils, Cattle, and Farm Environment in France (Burgundy Region). Front. Microbiol. 3:83. doi: 10.3389/fmicb.2012.00083
54. Hawkey, P. M., and Jones, A. M. (2009). The changing epidemiology of resistance. J. Antimicrob. Chemother. 64(Suppl. 1), i3-i10. doi: 10.1093/jac/dkp256
55. Hotchkiss, R. D. (1951). Transfer of penicillin resistance in pneumococci by the desoxyribonucleate derived from resistant cultures. Cold Spring Harb. Symp. Quant. Biol. 16, 457-461. doi: 10.1101/SQB.1951.016.01.032
56. Hu, Y., Liu, F., Lin, I. Y., Gao, G. F., and Zhu, B. (2015). Dissemination of the mcr-1 colistin resistance gene. Lancet Infect. Dis. 16, 146-147. doi: 10.1016/S1473-3099(15)00533-2
57. Huddleston, J. R. (2014). Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes. Infect. Drug Resist. 7, 167-176. doi: 10.2147/IDR.S48820
58. Humphrey, S. B., Stanton, T. B., Jensen, N. S., and Zuerner, R. L. (1997). Purification and characterization of VSH-1, a generalized transducing bacteriophage of Serpulina hyodysenteriae. J. Bacteriol. 179, 323-329.
59. Hyder, S. L., and Streitfeld, M. M. (1978). Transfer of erythromycin resistance from clinically isolated lysogenic strains of Streptococcus pyogenes via their endogenous phage. J. Infect. Dis. 138, 281-286. doi: 10.1093/infdis/138.3.281
60. Hynes, A. P., Mercer, R. G., Watton, D. E., Buckley, C. B., and Lang, A. S. (2012). DNA packaging bias and differential expression of gene transfer agent genes within a population during production and release of the Rhodobacter capsulatus gene transfer agent, RcGTA. Mol. Microbiol. 85, 314-325. doi: 10.1111/j.1365-2958.2012.08113.x
61. Janoir, C., Podglajen, I., Kitzis, M. D., Poyart, C., and Gutmann, L. (1999). In vitro exchange of fluoroquinolone resistance determinants between Streptococcus pneumoniae and viridans streptococci and genomic organization of the parE-parC region in S. mitis. J. Infect. Dis. 180, 555-558. doi: 10.1086/314888
62. Jensen, E. C., Schrader, H. S., Rieland, B., Thompson, T. L., Lee, K. W., Nickerson, K. W., et al. (1998). Prevalence of broad-host-range lytic bacteriophages of Sphaerotilus natans, Escherichia coli, and Pseudomonas aeruginosa. Appl. Environ. Microbiol. 64, 575-580.
63. Johnston, C., Martin, B., Fichant, G., Polard, P., and Claverys, J. P. (2014). Bacterial transformation: distribution, shared mechanisms and divergent control. Nat. Rev. Microbiol. 12, 181-196. doi: 10.1038/nrmicro3199
64. Kazimierczak, K. A., Scott, K. P., Kelly, D., and Aminov, R. I. (2009). Tetracycline resistome of the organic pig gut. Appl. Environ. Microbiol. 75, 1717-1722. doi: 10.1128/AEM.02206-08
65. Knapp, C. W., Dolfing, J., Ehlert, P. A., and Graham, D. W. (2010). Evidence of increasing antibiotic resistance gene abundances in archived soils since 1940. Environ. Sci. Technol. 44, 580-587. doi: 10.1021/es901221x
66. Kristensen, B. M., Sinha, S., Boyce, J. D., Bojesen, A. M., Mell, J. C., and Redfield, R. J. (2012). Natural transformation of Gallibacterium anatis. Appl. Environ. Microbiol. 78, 4914-4922. doi: 10.1128/AEM.00412-12
67. Kristiansson, E., Fick, J., Janzon, A., Grabic, R., Rutgersson, C., Weijdegard, B., et al. (2011). Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements. PLoS ONE 6:e17038. doi: 10.1371/journal.pone.0017038
68. Lang, A. S., and Beatty, J. T. (2000). Genetic analysis of a bacterial genetic exchange element: the gene transfer agent of Rhodobacter capsulatus. Proc. Natl. Acad. Sci. U.S.A. 97, 859-864. doi: 10.1073/pnas.97.2.859
69. Lang, A. S., and Beatty, J. T. (2001). The gene transfer agent of Rhodobacter capsulatus and "constitutive transduction" in prokaryotes. Arch. Microbiol. 175, 241-249. doi: 10.1007/s002030100260
70. Lang, A. S., and Beatty, J. T. (2007). Importance of widespread gene transfer agent genes in alpha-proteobacteria. Trends Microbiol. 15, 54-62. doi: 10.1016/j.tim.2006.12.001
71. Lang, A. S., Zhaxybayeva, O., and Beatty, J. T. (2012). Gene transfer agents: phage-like elements of genetic exchange. Nat. Rev. Microbiol. 10, 472-482. doi: 10.1038/nrmicro2802
72. Larsson, D. G., de Pedro, C., and Paxeus, N. (2007). Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J. Hazard. Mater. 148, 751-755. doi: 10.1016/j.jhazmat.2007.07.008
73. Le-Minh, N., Khan, S. J., Drewes, J. E., and Stuetz, R. M. (2010). Fate of antibiotics during municipal water recycling treatment processes. Water Res. 44, 4295-4323. doi: 10.1016/j.watres.2010.06.020
74. Leung, M. M., Brimacombe, C. A., Spiegelman, G. B., and Beatty, J. T. (2012). The GtaR protein negatively regulates transcription of the gtaRI operon and modulates gene transfer agent (RcGTA) expression in Rhodobacter capsulatus. Mol. Microbiol. 83, 759-774. doi: 10.1111/j.1365-2958.2011.07963.x
75. Linares, J. F., Gustafsson, I., Baquero, F., and Martinez, J. L. (2006). Antibiotics as intermicrobial signaling agents instead of weapons. Proc. Natl. Acad. Sci. U.S.A. 103, 19484-19489. doi: 10.1073/pnas.0608949103
76. Liu, Y. Y., Wang, Y., Walsh, T. R., Yi, L. X., Zhang, R., Spencer, J., et al. (2015). Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect. Dis. 16, 161-168. doi: 10.1016/S1473-3099(15)00424-7
77. Lujan, R., Zhang, Q. Y., Saez Nieto, J. A., Jones, D. M., and Spratt, B. G. (1991). Penicillin-resistant isolates of Neisseria lactamica produce altered forms of penicillin-binding protein 2 that arose by interspecies horizontal gene transfer. Antimicrob. Agents Chemother. 35, 300-304. doi: 10.1128/AAC.35.2.300
78. Mao, D., Luo, Y., Mathieu, J., Wang, Q., Feng, L., Mu, Q., et al. (2014). Persistence of extracellular DNA in river sediment facilitates antibiotic resistance gene propagation. Environ. Sci. Technol. 48, 71-78. doi: 10.1021/es404280v
79. Marathe, N. P., Regina, V. R., Walujkar, S. A., Charan, S. S., Moore, E. R., Larsson, D. G., et al. (2013). A treatment plant receiving waste water from multiple bulk drug manufacturers is a reservoir for highly multi-drug resistant integron-bearing bacteria. PLoS ONE 8:e77310. doi: 10.1371/journal.pone.0077310
80. Marrs, B. (1974). Genetic recombination in Rhodopseudomonas capsulata. Proc. Natl. Acad. Sci. U.S.A. 71, 971-973. doi: 10.1073/pnas.71.3.971
81. Marti, E., Variatza, E., and Balcazar, J. L. (2014). Bacteriophages as a reservoir of extended-spectrum β-lactamase and fluoroquinolone resistance genes in the environment. Clin. Microbiol. Infect. 20, O456-O459. doi: 10.1111/1469-0691.12446
82. Martinez, J. L. (2009). Environmental pollution by antibiotics and by antibiotic resistance determinants. Environ. Pollut. 157, 2893-2902. doi: 10.1016/j.envpol.2009.05.051
83. Martinez, J. L. (2008). Antibiotics and antibiotic resistance genes in natural environments. Science 321, 365-367. doi: 10.1126/science.1159483
84. Mazaheri Nezhad Fard, R., Barton, M. D., and Heuzenroeder, M. W. (2011). Bacteriophage-mediated transduction of antibiotic resistance in enterococci. Lett. Appl. Microbiol. 52, 559-564. doi: 10.1111/j.1472-765X.2011.03043.x
85. McDaniel, L. D., Young, E., Delaney, J., Ruhnau, F., Ritchie, K. B., and Paul, J. H. (2010). High frequency of horizontal gene transfer in the oceans. Science 330, 50. doi: 10.1126/science.1192243
86. Mercer, R. G., Quinlan, M., Rose, A. R., Noll, S., Beatty, J. T., and Lang, A. S. (2012). Regulatory systems controlling motility and gene transfer agent production and release in Rhodobacter capsulatus. FEMS Microbiol. Lett. 331, 53-62. doi: 10.1111/j.1574-6968.2012.02553.x
87. Meyer, R. (2009). Replication and conjugative mobilization of broad host-range IncQ plasmids. Plasmid 62, 57-70. doi: 10.1016/j.plasmid.2009.05.001
88. Modi, S. R., Lee, H. H., Spina, C. S., and Collins, J. (2013). Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499, 219-222. doi: 10.1038/nature12212
89. Moore, A. M., Ahmadi, S., Patel, S., Gibson, M. K., Wang, B., Ndao, M. I., et al. (2015). Gut resistome development in healthy twin pairs in the first year of life. Microbiome 3:27. doi: 10.1186/s40168-015-0090-9
90. Moore, A. M., Patel, S., Forsberg, K. J., Wang, B., Bentley, G., Razia, Y., et al. (2013). Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes. PLoS ONE 8:e78822. doi: 10.1371/journal.pone.0078822
91. Mori, T., Mizuta, S., Suenaga, H., and Miyazaki, K. (2008). Metagenomic screening for bleomycin resistance genes. Appl. Environ. Microbiol. 74, 6803-6805. doi: 10.1128/AEM.00873-08
92. Motro, Y., La, T., Bellgard, M. I., Dunn, D. S., Phillips, N. D., and Hampson, D. (2009). Identification of genes associated with prophage-like gene transfer agents in the pathogenic intestinal spirochaetes Brachyspira hyodysenteriae, Brachyspira pilosicoli and Brachyspira intermedia. Vet. Microbiol. 134, 340-345. doi: 10.1016/j.vetmic.2008.09.051
93. Munck, C., Albertsen, M., Telke, A., Ellabaan, M., Nielsen, P. H., and Sommer, M. O. (2015). Limited dissemination of the wastewater treatment plant core resistome. Nat. Commun. 6, 8452. doi: 10.1038/ncomms9452
94. Musovic, S., Oregaard, G., Kroer, N., and Sorensen, S. J. (2006). Cultivation-independent examination of horizontal transfer and host range of an IncP-1 plasmid among gram-positive and gram-negative bacteria indigenous to the barley rhizosphere. Appl. Environ. Microbiol. 72, 6687-6692. doi: 10.1128/AEM.00013-06
95. Nordmann, P., Dortet, L., and Poirel, L. (2012). Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends Mol. Med. 18, 263-272. doi: 10.1016/j.molmed.2012.03.003
96. Norman, A., Hansen, L. H., and Sorensen, S. J. (2009). Conjugative plasmids: vessels of the communal gene pool. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 2275-2289. doi: 10.1098/rstb.2009.0037
97. Parsley, L. C., Consuegra, E. J., Kakirde, K. S., Land, A. M., Harper, W. F. Jr., and Liles, M. R. (2010). Identification of diverse antimicrobial resistance determinants carried on bacterial, plasmid, or viral metagenomes from an activated sludge microbial assemblage. Appl. Environ. Microbiol. 76, 3753-3757. doi: 10.1128/AEM.03080-09
98. Pehrsson, E. C., Forsberg, K. J., Gibson, M. K., Ahmadi, S., and Dantas, G. (2013). Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs. Front. Microbiol. 4:145. doi: 10.3389/fmicb.2013.00145
99. Penders, J., and Stobberingh, E. E. (2008). Antibiotic resistance of motile aeromonads in indoor catfish and eel farms in the southern part of The Netherlands. Int. J. Antimicrob. Agents 31, 261-265. doi: 10.1016/j.ijantimicag.2007.10.002
100. Penders, J., Stobberingh, E. E., Savelkoul, P. H., and Wolffs, P. F. (2013). The human microbiome as a reservoir of antimicrobial resistance. Front. Microbiol. 4:87. doi: 10.3389/fmicb.2013.00087
101. Perron, G. G., Whyte, L., Turnbaugh, P. J., Goordial, J., Hanage, W. P., Dantas, G., et al. (2015). Functional characterization of bacteria isolated from ancient arctic soil exposes diverse resistance mechanisms to modern antibiotics. PLoS ONE 10:e0069533. doi: 10.1371/journal.pone.0069533
102. Pletz, M. W., McGee, L., Van Beneden, C. A., Petit, S., Bardsley, M., Barlow, M., et al. (2006). Fluoroquinolone resistance in invasive Streptococcus pyogenes isolates due to spontaneous mutation and horizontal gene transfer. Antimicrob. Agents Chemother. 50, 943-948. doi: 10.1128/AAC.50.3.943-948.2006
103. Poirel, L., Liard, A., Rodriguez-Martinez, J. M., and Nordmann, P. (2005b). Vibrionaceae as a possible source of Qnr-like quinolone resistance determinants. J. Antimicrob. Chemother. 56, 1118-1121. doi: 10.1093/jac/dki371
104. Poirel, L., Potron, A., and Nordmann, P. (2012). OXA-48-like carbapenemases: the phantom menace. J. Antimicrob. Chemother. 67, 1597-1606. doi: 10.1093/jac/dks121
105. Poirel, L., Rodriguez-Martinez, J. M., Mammeri, H., Liard, A., and Nordmann, P. (2005a). Origin of plasmid-mediated quinolone resistance determinant QnrA. Antimicrob. Agents Chemother. 49, 3523-3525. doi: 10.1128/AAC.49.8.3523-3525.2005
106. Prudhomme, M., Attaiech, L., Sanchez, G., Martin, B., and Claverys, J. P. (2006). Antibiotic stress induces genetic transformability in the human pathogen Streptococcus pneumoniae. Science 313, 89-92. doi: 10.1126/science.1127912
107. Quiros, P., Colomer-Lluch, M., Martinez-Castillo, A., Miro, E., Argente, M., Jofre, J., et al. (2014). Antibiotic resistance genes in the bacteriophage DNA fraction of human fecal samples. Antimicrob. Agents Chemother. 58, 606-609. doi: 10.1128/AAC.01684-13
108. Riesenfeld, C. S., Goodman, R. M., and Handelsman, J. (2004). Uncultured soil bacteria are a reservoir of new antibiotic resistance genes. Environ. Microbiol. 6, 981-989. doi: 10.1111/j.1462-2920.2004.00664.x
109. Rizzo, L., Manaia, C., Merlin, C., Schwartz, T., Dagot, C., Ploy, M. C., et al. (2013). Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment: a review. Sci. Total Environ. 447, 345-360. doi: 10.1016/j.scitotenv.2013.01.032
110. Roberts, A. P., and Mullany, P. (2009). A modular master on the move: the Tn916 family of mobile genetic elements. Trends Microbiol. 17, 251-258. doi: 10.1016/j.tim.2009.03.002
111. Rolain, J. M., Fancello, L., Desnues, C., and Raoult, D. (2011). Bacteriophages as vehicles of the resistome in cystic fibrosis. J. Antimicrob. Chemother. 66, 2444-2447. doi: 10.1093/jac/dkr318
112. Sarmah, A. K., Meyer, M. T., and Boxall, A. B. (2006). A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere 65, 725-759. doi: 10.1016/j.chemosphere.2006.03.026
113. Schmieger, H., and Schicklmaier, P. (1999). Transduction of multiple drug resistance of Salmonella enterica serovar typhimurium DT104. FEMS Microbiol. Lett. 170, 251-256. doi: 10.1111/j.1574-6968.1999.tb13381.x
114. Scolnik, P. A., and Haselkorn, R. (1984). Activation of extra copies of genes coding for nitrogenase in Rhodopseudomonas capsulata. Nature 307, 289-292. doi: 10.1038/307289a0
115. Shoemaker, N. B., Vlamakis, H., Hayes, K., and Salyers, A. A. (2001). Evidence for extensive resistance gene transfer among Bacteroides spp. and among Bacteroides and other genera in the human colon. Appl. Environ. Microbiol. 67, 561-568. doi: 10.1128/AEM.67.2.561-568.2001
116. Shousha, A., Awaiwanont, N., Sofka, D., Smulders, F. J., Paulsen, P., Szostak, M. P., et al. (2015). Bacteriophages isolated from chicken meat and the horizontal transfer of antimicrobial resistance genes. Appl. Environ. Microbiol. 81, 4600-4606. doi: 10.1128/AEM.00872-15
117. Sibold, C., Henrichsen, J., Konig, A., Martin, C., Chalkley, L., and Hakenbeck, R. (1994). Mosaic pbpX genes of major clones of penicillin-resistant Streptococcus pneumoniae have evolved from pbpX genes of a penicillin-sensitive Streptococcus oralis. Mol. Microbiol. 12, 1013-1023. doi: 10.1111/j.1365-2958.1994.tb01089.x
118. Smillie, C., Garcillan-Barcia, M. P., Francia, M. V., Rocha, E. P., and de la Cruz, F. (2010). Mobility of plasmids. Microbiol. Mol. Biol. Rev. 74, 434-452. doi: 10.1128/MMBR.00020-10
119. Solioz, M., Yen, H. C., and Marris, B. (1975). Release and uptake of gene transfer agent by Rhodopseudomonas capsulata. J. Bacteriol. 123, 651-657.
120. Sommer, M. O., Dantas, G., and Church, G. M. (2009). Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325, 1128-1131. doi: 10.1126/science.1176950
121. Sparling, P. F. (1966). Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. J. Bacteriol. 92, 1364-1371.
122. Spratt, B. G. (1988). Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae. Nature 332, 173-176. doi: 10.1038/332173a0
123. Spratt, B. G., Bowler, L. D., Zhang, Q. Y., Zhou, J., and Smith, J. M. (1992). Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species. J. Mol. Evol. 34, 115-125. doi: 10.1007/BF00182388
124. Spratt, B. G., Zhang, Q. Y., Jones, D. M., Hutchison, A., Brannigan, J. A., and Dowson, C. G. (1989). Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis. Proc. Natl. Acad. Sci. U.S.A. 86, 8988-8992. doi: 10.1073/pnas.86.22.8988
125. Stanton, T. B. (2007). Prophage-like gene transfer agents-novel mechanisms of gene exchange for Methanococcus, Desulfovibrio, Brachyspira, and Rhodobacter species. Anaerobe 13, 43-49. doi: 10.1016/j.anaerobe.2007.03.004
126. Stanton, T. B., Humphrey, S. B., Sharma, V. K., and Zuerner, R. L. (2008). Collateral effects of antibiotics: carbadox and metronidazole induce VSH-1 and facilitate gene transfer among Brachyspira hyodysenteriae strains. Appl. Environ. Microbiol. 74, 2950-2956. doi: 10.1128/AEM.00189-08
127. Stanton, T. B., Matson, E. G., and Humphrey, S. B. (2001). Brachyspira (Serpulina) hyodysenteriae gyrB mutants and interstrain transfer of coumermycin A(1) resistance. Appl. Environ. Microbiol. 67, 2037-2043. doi: 10.1128/AEM.67.5.2037-2043.2001
128. Tamminen, M., Virta, M., Fani, R., and Fondi, M. (2012). Large-scale analysis of plasmid relationships through gene-sharing networks. Mol. Biol. Evol. 29, 1225-1240. doi: 10.1093/molbev/msr292
129. Tennstedt, T., Szczepanowski, R., Braun, S., Puhler, A., and Schluter, A. (2003). Occurrence of integron-associated resistance gene cassettes located on antibiotic resistance plasmids isolated from a wastewater treatment plant. FEMS Microbiol. Ecol. 45, 239-252. doi: 10.1016/S0168-6496(03)00164-8
130. Thomas, C. M., and Nielsen, K. M. (2005). Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nat. Rev. Microbiol. 3, 711-721. doi: 10.1038/nrmicro1234
131. Torres-Cortes, G., Millan, V., Ramirez-Saad, H. C., Nisa-Martinez, R., Toro, N., and Martinez-Abarca, F. (2011). Characterization of novel antibiotic resistance genes identified by functional metagenomics on soil samples. Environ. Microbiol. 13, 1101-1114. doi: 10.1111/j.1462-2920.2010.02422.x
132. Ubukata, K., Konno, M., and Fujii, R. (1975). Transduction of drug resistance to tetracycline, chloramphenicol, macrolides, lincomycin and clindamycin with phages induced from Streptococcus pyogenes. J. Antibiot. 28, 681-688. doi: 10.7164/antibiotics.28.681
133. Van Boeckel, T. P., Brower, C., Gilbert, M., Grenfell, B. T., Levin, S. A., Robinson, T. P., et al. (2015). Global trends in antimicrobial use in food animals. Proc. Natl. Acad. Sci. U.S.A. 112, 5649-5654. doi: 10.1073/pnas.1503141112
134. Van Boeckel, T. P., Gandra, S., Ashok, A., Caudron, Q., Grenfell, B. T., Levin, S. A., et al. (2014). Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect. Dis. 14, 742-750. doi: 10.1016/S1473-3099(14)70780-7
135. Varga, M., Kuntova, L., Pantucek, R., Maslanova, I., Ruzickova, V., and Doskar, J. (2012). Efficient transfer of antibiotic resistance plasmids by transduction within methicillin-resistant Staphylococcus aureus USA300 clone. FEMS Microbiol. Lett. 332, 146-152. doi: 10.1111/j.1574-6968.2012.02589.x
136. Vien le, T. M., Minh, N. N., Thuong, T. C., Khuong, H. D., Nga, T. V., Thompson, C., et al. (2012). The co-selection of fluoroquinolone resistance genes in the gut flora of Vietnamese children. PLoS ONE 7:e42919. doi: 10.1371/journal.pone.0042919
137. von Wintersdorff, C. J., Penders, J., Stobberingh, E. E., Lashof, A. M., Hoebe, C. J., Savelkoul, P. H., et al. (2014). High rates of antimicrobial drug resistance gene acquisition after international travel, the Netherlands. Emerging Infect. Dis. 20, 649-657. doi: 10.3201/eid2004.131718
138. Wall, J. D., Weaver, P. F., and Gest, H. (1975). Gene transfer agents, bacteriophages, and bacteriocins of Rhodopseudomonas capsulata. Arch. Microbiol. 105, 217-224. doi: 10.1007/BF00447140
139. Watkinson, A. J., Murby, E. J., and Costanzo, S. D. (2007). Removal of antibiotics in conventional and advanced wastewater treatment: implications for environmental discharge and wastewater recycling. Water Res. 41, 4164-4176. doi: 10.1016/j.watres.2007.04.005
140. Westbye, A. B., Leung, M. M., Florizone, S. M., Taylor, T. A., Johnson, J. A., Fogg, P. C., et al. (2013). Phosphate concentration and the putative sensor kinase protein CckA modulate cell lysis and release of the Rhodobacter capsulatus gene transfer agent. J. Bacteriol. 195, 5025-5040. doi: 10.1128/JB.00669-13
141. Wichmann, F., Udikovic-Kolic, N., Andrew, S., and Handelsman, J. (2014). Diverse antibiotic resistance genes in dairy cow manure. MBio. 5:e01017. doi: 10.1128/mBio.01017-13
142. Woerther, P. L., Burdet, C., Chachaty, E., and Andremont, A. (2013). Trends in human fecal carriage of extended-spectrum β-lactamases in the community: toward the globalization of CTX-M. Clin. Microbiol. Rev. 26, 744-758. doi: 10.1128/CMR.00023-13
143. Wozniak, R. A., and Waldor, M. K. (2010). Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow. Nat. Rev. Microbiol. 8, 552-563. doi: 10.1038/nrmicro2382
144. Wright, G. D. (2010). Antibiotic resistance in the environment: a link to the clinic? Curr. Opin. Microbiol. 13, 589-594. doi: 10.1016/j.mib.2010.08.005
145. Wright, G. D., and Poinar, H. (2012). Antibiotic resistance is ancient: implications for drug discovery. Trends Microbiol. 20, 157-159. doi: 10.1016/j.tim.2012.01.002
146. Zhang, X. X., Zhang, T., Zhang, M., Fang, H. H., and Cheng, S. P. (2009). Characterization and quantification of class 1 integrons and associated gene cassettes in sewage treatment plants. Appl. Microbiol. Biotechnol. 82, 1169-1177. doi: 10.1007/s00253-009-1886-y