Emergence and Dispersion of Resistance Genes by the Aquatic Environment: a review

Document Type: Review Paper

Authors

1 Department of Pathology, Universidade Federal do Espirito Santo, P. O. Box 29043-900, Vitória, Brazil

2 Faculty of Medicine, Universidade de Vila Velha, P. O. Box 29102-920 Vila Velha, Brazil

Abstract

The association of the emergence of bacterial resistance to clinical environments is common; however, aquatic environments, especially the polluted ones, also play a key role in this regard. Aquatic environments can act as facilitator for the exchange of mobile elements, responsible for resisting antibiotics. They even may stimulate the emergence and selection of these elements through contaminants or the natural competition between bacterial phyla. Currently there is a large number of highly-reliable resistance genes, which is selected in aquatic environments, mostly due to several types of pollution, such as the mcr-1 gene that causes resistance to one of the antibiotics, available in the market, namely colistin. Thus, the present review aims to show a range of impacts capable of selecting bacterial resistance in the environment, thus clarifying this environment's role in dispersion of resistance.

Keywords


Abdi, S., Ranjbar, R., Hakemi Vala, M., Jonaidi, N., Baghery Bejestany, O. and Baghery Bejestany, F. (2014) Frequency of Bla TEM, Bla SHV, Bla CTX-M, and qnrA Among Escherichia Coli Isolated From Urinary Tract Infection. Archives of Clinical Infectious Diseases , 9 (1), 1–5.

Ahn, C., Yoon, S. S., Yong, T. S., Jeong, S. H. and Lee, K. (2016) The Resistance Mechanism and Clonal Distribution of Tigecycline-Nonsusceptible Klebsiella Pneumoniae Isolates in Korea. Yonsei Medical Journal, 57 (3), 641–646.

Audrain, B., Farag, M. A., Ryu, C.-M. and Ghigo, J.-M. (2015) Role of Bacterial Volatile Compounds in Bacterial Biology. FEMS Microbiology Reviews , 39 (2) March, 222–233.

Baker-Austin, C., Wright, M. S., Stepanauskas, R. and McArthur, J. V. (2006) Co-Selection of Antibiotic and Metal Resistance. Trends in Microbiology, 14 (4), 176–182.

Baquero, F., Martínez, J. L. and Cantón, R. (2008) Antibiotics and Antibiotic Resistance in Water Environments. Current Opinion in Biotechnology, 19 (3), 260–265.

Barriere, S. L. (2015) Clinical, Economic and Societal Impact of Antibiotic Resistance. Expert Opinion on Pharmacotherapy , 16 (2), 151–153.

Berglund, B., Khan, G. A., Lindberg, R., Fick, J. and Lindgren, P. E. (2014) Abundance and Dynamics of Antibiotic Resistance Genes and Integrons in Lake Sediment Microcosms. PLoS ONE, 9 (9), e108151 .

Brown-Jaque, M., Calero-Cáceres, W. and Muniesa, M. (2015) Transfer of Antibiotic-Resistance Genes via Phage-Related Mobile Elements. Plasmid , 79, 1–7.

Bruins, M. R., Kapil, S. and Oehme, F. W. (2000) Microbial Resistance to Metals in the Environment. Ecotoxicology and Environmental Safety , 45 (3), 198–207.

Cabello, F. C., Godfrey, H. P., Buschmann, A. H. and Dölz, H. J. (2016) Aquaculture as yet Another Environmental Gateway to the Development and Globalisation of Antimicrobial Resistance. The Lancet Infectious Diseases , 16 (7), e127–e133.

Canal, N., Meneghetti, K. L., Almeida, C. P. de, Rosa Bastos, M. da, Otton, L. M. and Corção, G. (2016) Characterization of the Variable Region in the Class 1 Integron of Antimicrobial-Resistant Escherichia Coli Isolated from Surface Water. Brazilian Journal of Microbiology , 47 (2), 337–344.

Capkin, E., Terzi, E. and Altinok, I. (2015) Occurrence of Antibiotic Resistance Genes in Culturable Bacteria Isolated from Turkish Trout Farms and Their Local Aquatic Environment. Diseases of Aquatic Organisms , 114 (2), 127–137.

Carlesse, F., Cappellano, P., Quiles, M. G., Menezes, L. C., Petrilli, A. S. and Pignatari, A. C. (2016) Clinical Relevance of Molecular Identification of Microorganisms and Detection of Antimicrobial Resistance Genes in Bloodstream Infections of Paediatric Cancer Patients. BMC Infectious Diseases , 16 (1), 462.

Cesare, A. Di, Eckert, E. M., Teruggi, A., Fontaneto, D., Bertoni, R., Callieri, C. and Corno, G. (2015) Constitutive Presence of Antibiotic Resistance Genes within the Bacterial Community of a Large Subalpine Lake. Molecular Ecology , 24 (15), 3888–3900.

Chen, B., Hao, L., Guo, X., Wang, N. and Ye, B. (2015) Prevalence of Antibiotic Resistance Genes of Wastewater and Surface Water in Livestock Farms of Jiangsu Province, China. Environmental Science & Pollution Research, 22 (18), 13950–13959.

Chu, C., Chiu, C.-H., Wang, Y.-H., Chen, C.-L., Hou, J.-N., Wang, Y.-R., Lin, T.-Y., Wang, M.-H. and Yang, T.-H. (2015) Serotype Distribution and Resistance Genes Associated with Macrolide and Fluoroquinolone Resistance in Streptococcus Agalactiae Isolates from a Hospital in Southern Taiwan. Biomedical Journal , 38 (215), e20.

Conte, D., Palmeiro, J. K., Silva Nogueira, K. da, Lima, T. M. R. de, Cardoso, M. A., Pontarolo, R., Degaut Pontes, F. L. and Dalla-Costa, L. M. (2017) Characterization of CTX-M Enzymes, Quinolone Resistance Determinants, and Antimicrobial Residues from Hospital Sewage, Wastewater Treatment Plant, and River Water. Ecotoxicology and Environmental Safety , 136 (18), 62–69.

Croucher, N. J., Harris, S. R., Fraser, C., Quail, M. A., Burton, J., Linden, M. van der, McGee, L., Gottberg, A. von, Song, J. H., Ko, K. S., Pichon, B., Baker, S., Parry, C. M., Lambertsen, L. M., Shahinas, D., Pillai, D. R., Mitchell, T. J., Dougan, G., Tomasz, A., Klugman, K. P., Parkhill, J., Hanage, W. P. and Bentley, S. D. (2011) Rapid Pneumococcal Evolution in Response to Clinical Interventions. Science , 331 (6016), 430–434.

Czekalski, N., Gascón Díez, E. and Bürgmann, H. (2014) Wastewater as a Point Source of Antibiotic-Resistance Genes in the Sediment of a Freshwater Lake. The ISME Journal , 8 (7), 1381–1390.

Dantas, G. and Sommer, M. O. a (2014) How to Fight Back against Antibiotic Resistance. American Scientist, 102 (1), 42–51.

Economou, V. and Gousia, P. (2015) Agriculture and Food Animals as a Source of Antimicrobial-Resistant Bacteria. Infection & Drug Resistance, 49.

Finley, R. L., Collignon, P., Larsson, D. G. J., McEwen, S. A., Li, X.-Z., Gaze, W. H., Reid-Smith, R., Timinouni, M., Graham, D. W. and Topp, E. (2013) The Scourge of Antibiotic Resistance: The Important Role of the Environment. Clinical Infectious Diseases , 57 (5), 704–710.

Forsberg, K. J., Patel, S., Gibson, M. K., Lauber, C. L., Knight, R., Fierer, N. and Dantas, G. (2014) Bacterial Phylogeny Structures Soil Resistomes across Habitats. Nature , 509 (7502), 612–616.

Furukawa, K., Ramesh, A., Zhou, Z., Weinberg, Z., Vallery, T., Winkler, W. C. and Breaker, R. R. (2015) Bacterial Riboswitches Cooperatively Bind Ni 2+ or Co 2+ Ions and Control Expression of Heavy Metal Transporters. Molecular Cell , 57 (6) ,1088–1098.

Gerdt, J. P. and Blackwell, H. E. (2014) Competition Studies Confirm Two Major Barriers That Can Preclude the Spread of Resistance to Quorum-Sensing Inhibitors in Bacteria. ACS Chemical Biology , 9 (10), 2291–2299.

Gibson, M. K., Forsberg, K. J. and Dantas, G. (2014) Improved Annotation of Antibiotic Resistance Determinants Reveals Microbial Resistomes Cluster by Ecology. The ISME journal , 9 (1), 1–10.

Gibson, M. K., Forsberg, K. J. and Dantas, G. (2015) Improved Annotation of Antibiotic Resistance Determinants Reveals Microbial Resistomes Cluster by Ecology. The ISME Journal , 9 (1), 207–216.

Gillings, M. R. (2014) Integrons: Past, Present, and Future. Microbiology and Molecular Biology Reviews , 78 (2), 257–277.

Gullberg, E., Albrecht, L. M., Karlsson, C., Sandegren, L. and Andersson, D. I. (2014) Selection of a Multidrug Resistance Plasmid by Sublethal Levels of Antibiotics and Heavy Metals. mBio , 5 (5), e01918-14-e01918-14.

He, L.-Y., Ying, G.-G., Liu, Y.-S., Su, H.-C., Chen, J., Liu, S.-S. and Zhao, J.-L. (2016) Discharge of Swine Wastes Risks Water Quality and Food Safety: Antibiotics and Antibiotic Resistance Genes from Swine Sources to the Receiving Environments. Environment International , 92–93,. 210–219.

Hibbing, M. E., Fuqua, C., Parsek, M. R. and Peterson, S. B. (2010) Bacterial Competition: Surviving and Thriving in the Microbial Jungle. Nature Reviews Microbiology , 8 (1), 15–25.

Hobman, J. L. and Crossman, L. C. (2015) Bacterial Antimicrobial Metal Ion Resistance. Journal of Medical Microbiology , 64 (5), 471–497.

Hocquet, D., Muller, A. and Bertrand, X. (2016) What Happens in Hospitals Does Not Stay in Hospitals: Antibiotic-Resistant Bacteria in Hospital Wastewater Systems. Journal of Hospital Infection , 93 (4), 395–402.

Hölzel, C. S., Müller, C., Harms, K. S., Mikolajewski, S., Schäfer, S., Schwaiger, K. and Bauer, J. (2012) Heavy Metals in Liquid Pig Manure in Light of Bacterial Antimicrobial Resistance. Environmental Research , 113, 21–27.

Hsu, J.-T., Chen, C.-Y., Young, C.-W., Chao, W.-L., Li, M.-H., Liu, Y.-H., Lin, C.-M. and Ying, C. (2014) Prevalence of Sulfonamide-Resistant Bacteria, Resistance Genes and Integron-Associated Horizontal Gene Transfer in Natural Water Bodies and Soils Adjacent to a Swine Feedlot in Northern Taiwan. Journal of Hazardous Materials , 277, 34–43.

Hsueh, P.-R., Chen, W.-H. and Luh, K.-T. (2005) Relationships between Antimicrobial Use and Antimicrobial Resistance in Gram-Negative Bacteria Causing Nosocomial Infections from 1991–2003 at a University Hospital in Taiwan. International Journal of Antimicrobial Agents , 26 (6), 463–472.

Hu, H., Johani, K., Gosbell, I. B., Jacombs, A. S. W., Almatroudi, A., Whiteley, G. S., Deva, A. K., Jensen, S. and Vickery, K. (2015) Intensive Care Unit Environmental Surfaces Are Contaminated by Multidrug-Resistant Bacteria in Biofilms: Combined Results of Conventional Culture, Pyrosequencing, Scanning Electron Microscopy, and Confocal Laser Microscopy. Journal of Hospital Infection , 91 (1), 35–44.

Huang, L., Xu, Y.-B., Xu, J.-X., Ling, J.-Y., Chen, J.-L., Zhou, J.-L., Zheng, L. and Du, Q.-P. (2017) Antibiotic Resistance Genes (ARGs) in Duck and Fish Production Ponds with Integrated or Non-Integrated Mode. Chemosphere , 168 (100), 1107–1114.

Huang, Y., Zhang, L., Tiu, L. and Wang, H. H. (2015) Characterization of Antibiotic Resistance in Commensal Bacteria from an Aquaculture Ecosystem. Frontiers in Microbiology, 6, p.914.

Huerta, B., Marti, E., Gros, M., López, P., Pompêo, M., Armengol, J., Barceló, D., Balcázar, J. L., Rodríguez-Mozaz, S. and Marcé, R. (2013) Exploring the Links between Antibiotic Occurrence, Antibiotic Resistance, and Bacterial Communities in Water Supply Reservoirs. Science of The Total Environment , 456–457, 161–170.

Ji, X., Shen, Q., Liu, F., Ma, J., Xu, G., Wang, Y. and Wu, M. (2012) Antibiotic Resistance Gene Abundances Associated with Antibiotics and Heavy Metals in Animal Manures and Agricultural Soils Adjacent to Feedlots in Shanghai; China. Journal of Hazardous Materials , 235–236, 178–185.

Jørgensen, P. S. (2016) Antibiotic Resistance Is the next Great Global Challenge - We Must Act Now , Global Economic Dynamics and the Biosphere, Royal Swedish Academy of Sciences.

Koch, G., Yepes, A., Förstner, K. U., Wermser, C., Stengel, S. T., Modamio, J., Ohlsen, K., Foster, K. R. and Lopez, D. (2014) Evolution of Resistance to a Last-Resort Antibiotic in Staphylococcus Aureus via Bacterial Competition. Cell , 158 (5), 1060–1071.

Laffite, A., Kilunga, P. I., Kayembe, J. M., Devarajan, N., Mulaji, C. K., Giuliani, G., Slaveykova, V. I. and Poté, J. (2016) Hospital Effluents Are One of Several Sources of Metal, Antibiotic Resistance Genes, and Bacterial Markers Disseminated in Sub-Saharan Urban Rivers. Frontiers in Microbiology ,  7, 1–14.

Leverstein–van Hall, M. A., Box, A. T. A., Blok, H. E. M., Paauw, A., Fluit, A. C. and Verhoef, J. (2002) Evidence of Extensive Interspecies Transfer of Integron‐Mediated Antimicrobial Resistance Genes among Multidrug‐Resistant Enterobacteriaceae in a Clinical Setting. The Journal of Infectious Diseases , 186 (1), 49–56.

Levin, A. S., Barone, A. A., Penço, J., Santos, M. V., Marinho, I. S., Arruda, E. A. G., Manrique, E. I. and Costa, S. F. (1999) Intravenous Colistin as Therapy for Nosocomial Infections Caused by Multidrug‐Resistant Pseudomonas Aeruginosa and Acinetobacter Baumannii. Clinical Infectious Diseases , 28 (5), 1008–1011.

Lindstedt, B.-A., Heir, E., Nygard, I. and Kapperud, G. (2003) Characterization of Class I Integrons in Clinical Strains of Salmonella Enterica Subsp. Enterica Serovars Typhimurium and Enteritidis from Norwegian Hospitals. Journal of Medical Microbiology , 52 (2), 141–149.

Liu, Y.-Y., Wang, Y., Walsh, T. R., Yi, L.-X., Zhang, R., Spencer, J., Doi, Y., Tian, G., Dong, B., Huang, X., Yu, L.-F., Gu, D., Ren, H., Chen, X., Lv, L., He, D., Zhou, H., Liang, Z., Liu, J.-H. and Shen, J. (2016) Emergence of Plasmid-Mediated Colistin Resistance Mechanism MCR-1 in Animals and Human Beings in China: A Microbiological and Molecular Biological Study. The Lancet Infectious Diseases , 16 (2), 161–168.

Manageiro, V., Ferreira, E., Caniça, M. and Manaia, C. M. (2014) GES-5 among the β -Lactamases Detected in Ubiquitous Bacteria Isolated from Aquatic Environment Samples. FEMS Microbiology Letters , 351 (1), 64–69.

Manning, M. Lou, Pfeiffer, J. and Larson, E. L. (2016) Combating Antibiotic Resistance: The Role of Nursing in Antibiotic Stewardship. American Journal of Infection Control , 44 (12), 1454–1457.

Manyahi, J., Tellevik, M. G., Ndugulile, F., Moyo, S. J., Langeland, N. and Blomberg, B. (2017) Molecular Characterization of Cotrimoxazole Resistance Genes and Their Associated Integrons in Clinical Isolates of Gram-Negative Bacteria from Tanzania. Microbial Drug Resistance , 23 (1), 37–43.

Mao, D., Luo, Y., Mathieu, J., Wang, Q., Feng, L., Mu, Q., Feng, C. and Alvarez, P. J. J. (2014) Persistence of Extracellular DNA in River Sediment Facilitates Antibiotic Resistance Gene Propagation. Environmental Science & Technology , 48 (1) 71–78.

Marathe, N. P., Regina, V. R., Walujkar, S. A., Charan, S. S., Moore, E. R. B., Larsson, D. G. J. and Shouche, Y. S. (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 (10),. e77310.

Martins, V. V., Zanetti, M. O. B., Pitondo-Silva, A. and Stehling, E. G. (2014) Aquatic Environments Polluted with Antibiotics and Heavy Metals: A Human Health Hazard. Environmental Science & Pollution Research , 21 (9), 5873–5878.

McGann, P., Snesrud, E., Maybank, R., Corey, B., Ong, A. C., Clifford, R., Hinkle, M., Whitman, T., Lesho, E. and Schaecher, K. E. (2016) Escherichia Coli Harboring Mcr-1 and Bla CTX-M on a Novel IncF Plasmid: First Report of Mcr-1 in the United States. Antimicrobial Agents& Chemotherapy , 60 (7), 4420–4421.

Molton, J. S., Tambyah, P. A., Ang, B. S. P., Ling, M. L. and Fisher, D. A. (2013) The Global Spread of Healthcare-Associated Multidrug-Resistant Bacteria: A Perspective from Asia. Clinical Infectious Diseases, 56 (9), 1310–1318.

Muñoz-Atienza, E., Gómez-Sala, B., Araújo, C., Campanero, C., Campo, R. del, Hernández, P. E., Herranz, C. and Cintas, L. M. (2013) Antimicrobial Activity, Antibiotic Susceptibility and Virulence Factors of Lactic Acid Bacteria of Aquatic Origin Intended for Use as Probiotics in Aquaculture. BMC microbiology , 13, p.15.

Muziasari, W. I., Pärnänen, K., Johnson, T. A., Lyra, C., Karkman, A., Stedtfeld3, R. D., Tamminen, M., Tiedje, J. M. and Virta, M. (2016) Aquaculture Changes the Profile of Antibiotic Resistance and Mobile Genetic Element Associated Genes in Baltic Sea Sediments. FEMS Microbiology Ecology Advance, 92 (4), 1–7.

Nathan, C. and Cunningham-bussel, A. (2013) Beyond Oxidative Stress : An Immunologist ’ S Guide to Reactive Oxygen Species. Nature Publishing Group , 13 (5), 349–361.

Ory, J., Bricheux, G., Togola, A., Bonnet, J. L., Donnadieu-Bernard, F., Nakusi, L., Forestier, C. and Traore, O. (2016) Ciprofloxacin Residue and Antibiotic-Resistant Biofilm Bacteria in Hospital Effluent. Environmental Pollution , 214, 635–645.

Ovejero, C. M., Delgado-Blas, J. F., Calero-Caceres, W., Muniesa, M. and Gonzalez-Zorn, B. (2017) Spread of Mcr-1 -Carrying Enterobacteriaceae in Sewage Water from Spain. Journal of Antimicrobial Chemotherapy , 72(4), 1050-1053. Pal, C., Bengtsson-Palme, J., Kristiansson, E. and Larsson, D. G. J. (2015) Co-Occurrence of Resistance Genes to Antibiotics, Biocides and Metals Reveals Novel Insights into Their Co-Selection Potential. BMC Genomics , 16 (1) p. 964.

Paltansing, S., Kraakman, M., Boxtel, R. van, Kors, I., Wessels, E., Goessens, W., Tommassen, J. and Bernards, A. (2015) Increased Expression Levels of Chromosomal AmpC β-Lactamase in Clinical Escherichia Coli Isolates and Their Effect on Susceptibility to Extended-Spectrum Cephalosporins. Microbial Drug Resistance , 21 (1), 7–16.

Phukan, C., Lahkar, M., Ranotkar, S. and Saikia, K. (2016) Emergence of vanA Gene among Vancomycin-Resistant Enterococci in a Tertiary Care Hospital of North - East India. Indian Journal of Medical Research , 143 (3), p. 357.

Proia, L., Schiller, D. von, Sànchez-Melsió, A., Sabater, S., Borrego, C. M., Rodríguez-Mozaz, S. and Balcázar, J. L. (2016) Occurrence and Persistence of Antibiotic Resistance Genes in River Biofilms after Wastewater Inputs in Small Rivers. Environmental Pollution , 210, 121–128.

Rafraf, I. D., Lekunberri, I., Sànchez-Melsió, A., Aouni, M., Borrego, C. M. and Balcázar, J. L. (2016) Abundance of Antibiotic Resistance Genes in Five Municipal Wastewater Treatment Plants in the Monastir Governorate, Tunisia. Environmental Pollution , 219, 353–358.

Ribeiro, V. B., Zavascki, A. P., Rozales, F. P., Pagano, M., Magagnin, C. M., Nodari, C. S., Silva, R. C. F. da, Dalarosa, M. G., Falci, D. R. and Barth, A. L. (2014) Detection of blaGES-5 in Carbapenem-Resistant Kluyvera Intermedia Isolates Recovered from the Hospital Environment. Antimicrobial Agents and Chemotherapy , 58 (1), 622–623.

Rico, A. and Brink, P. J. Van den (2014) Probabilistic Risk Assessment of Veterinary Medicines Applied to Four Major Aquaculture Species Produced in Asia. Science of The Total Environment , 468–469, 630–641.

Roca, I., Akova, M., Baquero, F., Carlet, J., Cavaleri, M., Coenen, S., Cohen, J., Findlay, D., Gyssens, I., Heure, O. E., Kahlmeter, G., Kruse, H., Laxminarayan, R., Liébana, E., López-Cerero, L., MacGowan, A., Martins, M., Rodríguez-Baño, J., Rolain, J.-M., Segovia, C., Sigauque, B., Tacconelli, E., Wellington, E. and Vila, J. (2015) The Global Threat of Antimicrobial Resistance: Science for Intervention. New Microbes and New Infections , 6, 22–29.

Rowe, W., Verner-Jeffreys, D. W., Baker-Austin, C., Ryan, J. J., Maskell, D. J. and Pearce, G. P. (2016) Comparative Metagenomics Reveals a Diverse Range of Antimicrobial Resistance Genes in Effluents Entering a River Catchment. Water Science & Technology , 73 (7), 1541–1549.

Seyedmonir, E., Yilmaz, F. and Icgen, B. (2015) mecA Gene Dissemination Among Staphylococcal and Non-Staphylococcal Isolates Shed in Surface Waters. Bulletin of Environmental Contamination and Toxicology , 95 (1), 131–138.

Shah, S. Q. A., Cabello, F. C., L’Abée-Lund, T. M., Tomova, A., Godfrey, H. P., Buschmann, A. H. and Sørum, H. (2014) Antimicrobial Resistance and Antimicrobial Resistance Genes in Marine Bacteria from Salmon Aquaculture and Non-Aquaculture Sites. Environmental Microbiology , 16 (5), 1310–1320.

Shiban, E., Janssen, I., Wostrack, M., Krieg, S. M., Horanin, M., Stoffel, M., Meyer, B. and Ringel, F. (2014) Spondylodiscitis by Drug-Multiresistant Bacteria: A Single-Center Experience of 25 Cases. The Spine Journal , 14 (12), 2826–2834.

Simo Tchuinte, P. L., Stalder, T., Venditti, S., Ngandjio, A., Dagot, C., Ploy, M.-C. and Barraud, O. (2016) Characterisation of Class 3 Integrons with Oxacillinase Gene Cassettes in Hospital Sewage and Sludge Samples from France and Luxembourg. International Journal of Antimicrobial Agents , 48 (4), 431–434.

Sorlozano, A., Jimenez-Pacheco, A., Dios Luna del Castillo, J. de, Sampedro, A., Martinez-Brocal, A., Miranda-Casas, C., Navarro-Marí, J. M. and Gutiérrez-Fernández, J. (2014) Evolution of the Resistance to Antibiotics of Bacteria Involved in Urinary Tract Infections: A 7-Year Surveillance Study. American Journal of Infection Control , 42 (10), 1033–1038.

Stalder, T., Barraud, O., Jové, T., Casellas, M., Gaschet, M., Dagot, C. and Ploy, M.-C. (2014) Quantitative and Qualitative Impact of Hospital Effluent on Dissemination of the Integron Pool. The ISME Journal , 8 (4), 768–777.

Stange, C., Sidhu, J. P. S., Tiehm, A. and Toze, S. (2016) Antibiotic Resistance and Virulence Genes in Coliform Water Isolates. International Journal of Hygiene & Environmental Health , 219 (8), 823–831.

Stone, L. K., Baym, M., Lieberman, T. D., Chait, R., Clardy, J. and Kishony, R. (2016) Compounds That Select against the Tetracycline-Resistance Efflux Pump. Nature Chemical Biology , 12 (11), 902–904.

Teichmann, A., Agra, H. N. de C., Nunes, L. de S., Rocha, M. P. da, Renner, J. D. P., Possuelo, L. G., Carneiro, M., Rieger, A., Benitez, L. B. and Valim, A. R. de M. (2014) Antibiotic Resistance and Detection of the sul2 Gene in Urinary Isolates of Escherichia Coli in Patients from Brazil. The Journal of Infection in Developing Countries , 8 (1), 39–43.

Tomova, A., Ivanova, L., Buschmann, A. H., Rioseco, M. L., Kalsi, R. K., Godfrey, H. P. and Cabello, F. C. (2015) Antimicrobial Resistance Genes in Marine Bacteria and Human Uropathogenic E Scherichia Coli from a Region of Intensive Aquaculture. Environmental Microbiology Reports , 7 (5), 803–809.

Tschudin-Sutter, S., Tamma, P. D., Naegeli, A. N., Speck, K. a., Milstone, A. M. and Perl, T. M. (2013) Distinguishing Community-Associated from Hospital-Associated Clostridium Difficile Infections in Children: Implications for Public Health Surveillance. Clinical Infectious Diseases, 57 (12), 1665–1672.

Vargas-Bautista, C., Rahlwes, K. and Straight, P. (2014) Bacterial Competition Reveals Differential Regulation of the Pks Genes by Bacillus Subtilis. Journal of Bacteriology , 196 (4), 717–728.

Vaz-Moreira, I., Varela, A. R., Pereira, T. V., Fochat, R. C. and Manaia, C. M. (2016) Multidrug Resistance in Quinolone-Resistant Gram-Negative Bacteria Isolated from Hospital Effluent and the Municipal Wastewater Treatment Plant. Microbial Drug Resistance , 22 (2), 155–163.

Verma, T., Srinath, T., Gadpayle, R. ., Ramteke, P. ., Hans, R. . and Garg, S. . (2001) Chromate Tolerant Bacteria Isolated from Tannery Effluent. Bioresource Technology , 78 (1), 31–35.

Wang, L., Gutek, A., Grewal, S., Michel, F. C. and Yu, Z. (2015) Changes in Diversity of Cultured Bacteria Resistant to Erythromycin and Tetracycline in Swine Manure during Simulated Composting and Lagoon Storage. Letters in Applied Microbiology , 61 (3), 245–251.

Wanjugi, P. and Harwood, V. J. (2013) The Influence of Predation and Competition on the Survival of Commensal and Pathogenic Fecal Bacteria in Aquatic Habitats. Environmental Microbiology , 15 (2), 517–526.

Wellington, E. M. H., Boxall, A. B. A., Cross, P., Feil, E. J., Gaze, W. H., Hawkey, P. M., Johnson-Rollings, A. S., Jones, D. L., Lee, N. M., Otten, W., Thomas, C. M. and Williams, A. P. (2013) The Role of the Natural Environment in the Emergence of Antibiotic Resistance in Gram-Negative Bacteria. The Lancet Infectious Diseases , 13 (2), 155–165.

Wintersdorff, C. J. H. von, Penders, J., Niekerk, J. M. van, Mills, N. D., Majumder, S., Alphen, L. B. van, Savelkoul, P. H. M. and Wolffs, P. F. G. (2016) Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer. Frontiers in Microbiology , 7, p.173.

World Economic Forum (WEF) (2013) Global Risks Report 2013 Eighth Edition . ISBN: 92-95044-50-9 978-92-95044-50-0 REF: 30121 Authors: WEF in collaboration with Oxford Martin School and partners.

World Health Organization (2015) Global Action Plan on Antimicrobial Resistance. WHO Press , 1–28, ISBN 978 92 4 150976 3.

Wu, J.-J., Ko, W.-C., Tsai, S.-H. and Yan, J.-J. (2007) Prevalence of Plasmid-Mediated Quinolone Resistance Determinants QnrA, QnrB, and QnrS among Clinical Isolates of Enterobacter Cloacae in a Taiwanese Hospital. Antimicrobial Agents and Chemotherapy , 51 (4), 1223–1227.

Xiong, W., Sun, Y., Zhang, T., Ding, X., Li, Y., Wang, M. and Zeng, Z. (2015) Antibiotics, Antibiotic Resistance Genes, and Bacterial Community Composition in Fresh Water Aquaculture Environment in China. Microbial Ecology , 70 (2), 425–432.

Xu, J., Xu, Y., Wang, H., Guo, C., Qiu, H., He, Y., Zhang, Y., Li, X. and Meng, W. (2015) Occurrence of Antibiotics and Antibiotic Resistance Genes in a Sewage Treatment Plant and Its Effluent-Receiving River. Chemosphere , 119, 1379–1385.

Yang, C.-W., Chang, Y.-T., Chao, W.-L., Shiung, I., Lin, H.-S., Chen, H., Ho, S.-H., Lu, M.-J., Lee, P.-H. and Fan, S.-N. (2014) An Investigation of Total Bacterial Communities, Culturable Antibiotic-Resistant Bacterial Communities and Integrons in the River Water Environments of Taipei City. Journal of Hazardous Materials , 277, 159–168.

Yazdankhah, S., Rudi, K. and Bernhoft, A. (2014) Zinc and Copper in Animal Feed – Development of Resistance and Co-Resistance to Antimicrobial Agents in Bacteria of Animal Origin. Microbial Ecology in Health & Disease , 25(1), p.25862.

Young, S., Nayak, B., Sun, S., Badgley, B. D., Rohr, J. R. and Harwood, V. J. (2016) Vancomycin-Resistant Enterococci and Bacterial Community Structure Following a Sewage Spill into an Aquatic Environment. Applied & Environmental Microbiology , 82 (18), 5653–5660.

Yugendran, T. and Harish, B. N. (2016) High Incidence of Plasmid-Mediated Quinolone Resistance Genes among Ciprofloxacin-Resistant Clinical Isolates of Enterobacteriaceae at a Tertiary Care Hospital in Puducherry, India. PeerJ , 4,  e1995.

Zhang, Q.-Q., Ying, G.-G., Pan, C.-G., Liu, Y.-S. and Zhao, J.-L. (2015) Comprehensive Evaluation of Antibiotics Emission and Fate in the River Basins of China: Source Analysis, Multimedia Modeling, and Linkage to Bacterial Resistance. Environmental Science & Technology , 49 (11), 6772–6782.

Zhu, Y.-G., Johnson, T. A., Su, J.-Q., Qiao, M., Guo, G.-X., Stedtfeld, R. D., Hashsham, S. A. and Tiedje, J. M. (2013) Diverse and Abundant Antibiotic Resistance Genes in Chinese Swine Farms. Proceedings of the National Academy of Sciences , 110 (9), 3435–3440.

Zurfuh, K., Poirel, L., Nordmann, P., Nüesch-Inderbinen, M., Hächler, H. and Stephan, R. (2016) Occurrence of the Plasmid-Borne Mcr-1 Colistin Resistance Gene in Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in River Water and Imported Vegetable Samples in Switzerland.. Antimicrobial Agents and Chemotherapy , 60 (4), 2594–2595.