Antibiotic Resistance Genes and Correlations with Microbial Community and Metal Resistance Genes in Full-Scale Biogas Reactors As Revealed by Metagenomic Analysis

Environmental Science and Technology

Volumn 51, Issue 7, 2017, Pages 4069-4080

  Luo, Gang ^a   Li, Bing ^b   Li, Li Guan ^c   Zhang, Tong ^c   Angelidaki, Irini ^d  

^a FUDAN UNIVERSITY   (China)

^b TSINGHUA UNIVERSITY   (China)

^c UNIVERSITY OF HONG KONG   (Hong Kong)

^d TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ANAEROBIC DIGESTION; ANTIBIOTICS; BIOGAS; CROPS; CULTIVATION; FATTY ACIDS; FERTILIZERS; GENES; HEALTH RISKS; MANURES; METAL ANALYSIS; MICROORGANISMS; RNA; VOLATILE FATTY ACIDS;

ANTIBIOTIC RESISTANCE GENES; CANONICAL CORRESPONDENCE ANALYSIS; ENVIRONMENTAL VARIABLES; HIGH-THROUGHPUT SEQUENCING; HYDRAULIC RETENTION TIME; MICROBIAL COMMUNITY COMPOSITION; THERMOPHILIC ANAEROBIC DIGESTION; VOLATILE FATTY ACIDS (VFAS);

PRINCIPAL COMPONENT ANALYSIS;

BIOGAS; METAL; VOLATILE FATTY ACID; ANTIINFECTIVE AGENT; BIOFUEL;

ABUNDANCE ESTIMATION; ANTIBIOTIC RESISTANCE; BIOGAS; BIOREACTOR; BIOTECHNOLOGY; CORRELATION; GENE; GENETIC ANALYSIS; GENOMICS; METAL; MICROBIAL COMMUNITY; MICROBIAL ECOLOGY; POLLUTANT REMOVAL; THERMOPHILIC BACTERIUM;

ANAEROBIC DIGESTION; ANTIBIOTIC RESISTANCE; ARTICLE; BIOREACTOR; CORRESPONDENCE ANALYSIS; GENE SEQUENCE; GENETIC ANALYSIS; HIGH THROUGHPUT SEQUENCING; METAGENOMICS; MICROBIAL COMMUNITY; NONHUMAN; PREVALENCE; PRINCIPAL COMPONENT ANALYSIS; WASTE WATER MANAGEMENT; BACTERIAL GENE; GENETICS; METAGENOME;

ANTI-BACTERIAL AGENTS; BIOFUELS; DRUG RESISTANCE, MICROBIAL; GENES, BACTERIAL; METAGENOME; METALS;

EID: 85019656562     PISSN: 0013936X     EISSN: 15205851     Source Type: Journal    
DOI: 10.1021/acs.est.6b05100     Document Type: Article

References (75)

1. Bibby, K.; Viau, E.; Peccia, J. Pyrosequencing of the 16S rRNA gene to reveal bacterial pathogen diversity in biosolids Water Res. 2010, 44 (14) 4252-4260 10.1016/j.watres.2010.05.039
2. Teglia, C.; Tremier, A.; Martel, J. L. Characterization of solid digestates: Part 1, Review of existing indicators to assess solid digestates agricultural use Waste Biomass Valorization 2011, 2 (1) 43-58 10.1007/s12649-010-9051-5
3. Ma, Y. J.; Wilson, C. A.; Novak, J. T.; Riffat, R.; Aynur, S.; Murthy, S.; Pruden, A. Effect of various sludge digestion conditions on sulfonamide, macrolide, and tetracycline resistance genes and Class I integrons Environ. Sci. Technol. 2011, 45 (18) 7855-7861 10.1021/es200827t
4. Andersson, D. I.; Hughes, D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat. Rev. Microbiol. 2010, 8 (4) 260-271 10.1038/nrmicro2319
5. Pruden, A.; Pei, R.; Storteboom, H.; Carlson, K. H. Antibiotic resistance genes as emerging contaminants: Studies in northern Colorado Environ. Sci. Technol. 2006, 40 (23) 7445-7450 10.1021/es060413l
6. Knapp, C. W.; Dolfing, J.; Ehlert, P. A. I.; Graham, D. W. Evidence of increasing antibiotic resistance gene abundances in archived soils since 1940 Environ. Sci. Technol. 2010, 44 (2) 580-587 10.1021/es901221x
7. Zhu, Y. G.; Johnson, T. A.; Su, J. Q.; Qiao, M.; Guo, G. X.; Stedtfeld, R. D.; Hashsham, S. A.; Tiedje, J. M. Diverse and abundant antibiotic resistance genes in Chinese swine farms Proc. Natl. Acad. Sci. U. S. A. 2013, 110 (9) 3435-3440 10.1073/pnas.1222743110
8. Fang, H.; Wang, H.; Cai, L.; Yu, Y. Prevalence of antibiotic resistance genes and bacterial pathogens in long-term manured greenhouse soils as revealed by metagenomic survey Environ. Sci. Technol. 2015, 49 (2) 1095-1104 10.1021/es504157v
9. Seiler, C.; Berendonk, T. U. Heavy metal driven co-selection of antibiotic resistance in soil and water bodies impacted by agriculture and aquaculture Front. Microbiol. 2012, 3, 399 10.3389/fmicb.2012.00399
10. Baker-Austin, C.; Wright, M. S.; Stepanauskas, R.; McArthur, J. V. Co-selection of antibiotic and metal resistance Trends Microbiol. 2006, 14 (4) 176-182 10.1016/j.tim.2006.02.006
11. Berg, J.; Thorsen, M. K.; Holm, P. E.; Jensen, J.; Nybroe, O.; Brandt, K. K. Cu Exposure under field conditions coselects for antibiotic resistance as determined by a novel cultivation-independent bacterial community tolerance assay Environ. Sci. Technol. 2010, 44 (22) 8724-8728 10.1021/es101798r
12. Forsberg, K. J.; Reyes, A.; Wang, B.; Selleck, E. M.; Sommer, M. O. A.; Dantas, G. The shared antibiotic resistome of soil bacteria and human pathogens Science 2012, 337 (6098) 1107-1111 10.1126/science.1220761
13. Shi, P.; Jia, S. Y.; Zhang, X. X.; Zhang, T.; Cheng, S. P.; Li, A. M. Metagenomic insights into chlorination effects on microbial antibiotic resistance in drinking water Water Res. 2013, 47 (1) 111-120 10.1016/j.watres.2012.09.046
14. Kristiansson, E.; Fick, J.; Janzon, A.; Grabic, R.; Rutgersson, C.; Weijdegard, B.; Soderstrom, H.; Larsson, D. G. J. Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements PLoS One 2011, 6 (2) e17038 10.1371/journal.pone.0017038
15. Smillie, C. S.; Smith, M. B.; Friedman, J.; Cordero, O. X.; David, L. A.; Alm, E. J. Ecology drives a global network of gene exchange connecting the human microbiome Nature 2011, 480 (7376) 241-244 10.1038/nature10571
16. Stokes, H. W.; Gillings, M. R. Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gram-negative pathogens FEMS Microbiol. Rev. 2011, 35 (5) 790-819 10.1111/j.1574-6976.2011.00273.x
17. Weaver, K. E.; Kwong, S. M.; Firth, N.; Francia, M. V. The replicons of Gram-positive bacteria: A family of broadly distributed but narrow host range plasmids Plasmid 2009, 61 (2) 94-109 10.1016/j.plasmid.2008.11.004
18. Forsberg, K. J.; Patel, S.; Gibson, M. K.; Lauber, C. L.; Knight, R.; Fierer, N.; Dantas, G. Bacterial phylogeny structures soil resistomes across habitats Nature 2014, 509 (7502) 612-616 10.1038/nature13377
19. Diehl, D. L.; LaPara, T. M. Effect of temperature on the fate of genes encoding tetracycline resistance and the integrase of Class 1 integrons within anaerobic and aerobic digesters treating municipal wastewater solids Environ. Sci. Technol. 2010, 44 (23) 9128-9133 10.1021/es102765a
20. Ye, L.; Zhang, T. Pathogenic bacteria in sewage treatment plants as revealed by 454 pyrosequencing Environ. Sci. Technol. 2011, 45 (17) 7173-7179 10.1021/es201045e
21. Luo, G.; Angelidaki, I. Analysis of bacterial communities and bacterial pathogens in a biogas plant by the combination of ethidium monoazide, PCR and Ion Torrent sequencing Water Res. 2014, 60, 156-163 10.1016/j.watres.2014.04.047
22. Li, B.; Yang, Y.; Ma, L.; Ju, F.; Guo, F.; Tiedje, J. M.; Zhang, T. Metagenomic and network analysis reveal wide distribution and co-occurrence of environmental antibiotic resistance genes ISME J. 2015, 9 (11) 2490-2502 10.1038/ismej.2015.59
23. Fierer, N.; Leff, J. W.; Adams, B. J.; Nielsen, U. N.; Bates, S. T.; Lauber, C. L.; Owens, S.; Gilbert, J. A.; Wall, D. H.; Caporaso, J. G. Cross-biome metagenomic analyses of soil microbial communities and their functional attributes Proc. Natl. Acad. Sci. U. S. A. 2012, 109 (52) 21390-21395 10.1073/pnas.1215210110
24. Bassani, I.; Kougias, P. G.; Treu, L.; Angelidaki, I. Biogas upgrading via hydrogenotrophic methanogenesis in two-stage continuous stirred tank reactors at mesophilic and thermophilic conditions Environ. Sci. Technol. 2015, 49 (20) 12585-12593 10.1021/acs.est.5b03451
25. Ye, L.; Zhang, T.; Wang, T. T.; Fang, Z. W. Microbial structures, functions, and metabolic pathways in wastewater treatment bioreactors revealed using high-throughput sequencing Environ. Sci. Technol. 2012, 46 (24) 13244-13252 10.1021/es303454k
26. Yang, Y.; Li, B.; Ju, F.; Zhang, T. Exploring variation of antibiotic resistance genes in activated sludge over a four-year period through a metagenomic approach Environ. Sci. Technol. 2013, 47 (18) 10197-10205 10.1021/es4017365
27. Raven, R. P. J. M.; Gregersen, K. H. Biogas plants in Denmark: successes and setbacks Renewable Sustainable Energy Rev. 2007, 11 (1) 116-132 10.1016/j.rser.2004.12.002
28. Jensen, J.; Jepsen, S. E. The production, use and quality of sewage sludge in Denmark Waste Manage. 2005, 25 (3) 239-247 10.1016/j.wasman.2004.08.011
29. Yang, Y.; Jiang, X.; Chai, B.; Ma, L.; Li, B.; Zhang, A.; Cole, J. R.; Tiedje, J. M.; Zhang, T. ARGs-OAP: online analysis pipeline for antibiotic resistance genes detection from metagenomic data using an integrated structured ARG-database Bioinformatics 2016, 32, 2346 10.1093/bioinformatics/btw136
30. Yi, Q.; Zhang, Y.; Gao, Y.; Tian, Z.; Yang, M. Anaerobic treatment of antibiotic production wastewater pretreated with enhanced hydrolysis: Simultaneous reduction of COD and ARGs Water Res. 2017, 110, 211-217 10.1016/j.watres.2016.12.020
31. Nobel, Y. R.; Cox, L. M.; Kirigin, F. F.; Bokulich, N. A.; Yamanishi, S.; Teitler, I.; Chung, J.; Sohn, J.; Barber, C. M.; Goldfarb, D. S.; Raju, K.; Abubucker, S.; Zhou, Y.; Ruiz, V. E.; Li, H.; Mitreva, M.; Alekseyenko, A. V.; Weinstock, G. M.; Sodergren, E.; Blaser, M. J. Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment Nat. Commun. 2015, 6, 7486 10.1038/ncomms8486
32. Korpela, K.; Salonen, A.; Virta, L. J.; Kekkonen, R. A.; Forslund, K.; Bork, P.; de Vos, W. M. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children Nat. Commun. 2016, 7, 10410 10.1038/ncomms10410
33. Zaura, E.; Brandt, B. W.; Teixeira de Mattos, M. J.; Buijs, M. J.; Caspers, M. P. M.; Rashid, M.-U.; Weintraub, A.; Nord, C. E.; Savell, A.; Hu, Y.; Coates, A. R.; Hubank, M.; Spratt, D. A.; Wilson, M.; Keijser, B. J. F.; Crielaard, W. Same exposure but two radically different responses to antibiotics: Resilience of the salivary microbiome versus long-term microbial shifts in feces mBio 2015, 6 (6) e01693 10.1128/mBio.01693-15
34. Fitzpatrick, D.; Walsh, F. Antibiotic resistance genes across a wide variety of metagenomes FEMS Microbiol. Ecol. 2016, 92 (2) fiv168 10.1093/femsec/fiv168
35. Wang, H.; Sangwan, N.; Li, H. Y.; Su, J. Q.; Oyang, W. Y.; Zhang, Z. J.; Gilbert, J. A.; Zhu, Y. G.; Ping, F.; Zhang, H. L. The antibiotic resistome of swine manure is significantly altered by association with the Musca domestica larvae gut microbiome ISME J. 2017, 11 (1) 100-111 10.1038/ismej.2016.103
36. Liu, B.; Pop, M. ARDB-Antibiotic resistance genes database Nucleic Acids Res. 2009, 37 (suppl 1) D443-D447 10.1093/nar/gkn656
37. Li, A. D.; Li, L. G.; Zhang, T. Exploring antibiotic resistance genes and metal resistance genes in plasmid metagenomes from wastewater treatment plants Front. Microbiol. 2015, 6, 1025 10.3389/fmicb.2015.01025
38. Li, L. G.; Cai, L.; Zhang, X. X.; Zhang, T. Potentially novel copper resistance genes in copper-enriched activated sludge revealed by metagenomic analysis Appl. Microbiol. Biotechnol. 2014, 98 (24) 10255-10266 10.1007/s00253-014-5939-5
39. Segata, N.; Waldron, L.; Ballarini, A.; Narasimhan, V.; Jousson, O.; Huttenhower, C. Metagenomic microbial community profiling using unique clade-specific marker genes Nat. Methods 2012, 9 (8) 811-814 10.1038/nmeth.2066
40. Junker, B. H.; Schreiber, F. Correlation networks. In Analysis of Biological Networks; Wiley-Interscience: Hoboken, NJ, 2008.
41. Bastian, M.; Heymann, S.; Jacomy, M. Gephi: an open source software for exploring and manipulating networks Proc. Third Inter. ICWSM Conf. 2009, 8, 361-362
42. APHA. Standard methods for the examination of water and wastewater, 19 th ed.; American Public Health Association: New York, USA, 1995.
43. Luo, G.; Talebnia, F.; Karakashev, D.; Xie, L.; Zhou, Q.; Angelidaki, I. Enhanced bioenergy recovery from rapeseed plant in a biorefinery concept Bioresour. Technol. 2011, 102 (2) 1433-1439 10.1016/j.biortech.2010.09.071
44. Karakashev, D.; Batstone, D. J.; Angelidaki, I. Influence of environmental conditions on methanogenic compositions in anaerobic biogas reactors Appl. Environ. Microbiol. 2005, 71 (1) 331-338 10.1128/AEM.71.1.331-338.2005
45. Looft, T.; Johnson, T. A.; Allen, H. K.; Bayles, D. O.; Alt, D. P.; Stedtfeld, R. D.; Sul, W. J.; Stedtfeld, T. M.; Chai, B.; Cole, J. R.; Hashsham, S. A.; Tiedje, J. M.; Stanton, T. B. In-feed antibiotic effects on the swine intestinal microbiome Proc. Natl. Acad. Sci. U. S. A. 2012, 109 (5) 1691-1696 10.1073/pnas.1120238109
46. Trapnell, B. C.; McColley, S. A.; Kissner, D. G.; Rolfe, M. W.; Rosen, J. M.; McKevitt, M.; Moorehead, L.; Montgomery, A. B.; Geller, D. E. Fosfomycin/Tobramycin for inhalation in patients with cystic fibrosis with Pseudomonas airway infection Am. J. Respir. Crit. Care Med. 2012, 185 (2) 171-178 10.1164/rccm.201105-0924OC
47. Borrmann, S.; Adegnika, A. A.; Matsiegui, P.-B.; Issifou, S.; Schindler, A.; Mawili-Mboumba, D. P.; Baranek, T.; Wiesner, J.; Jomaa, H.; Kremsner, P. G. Fosmidomycin-clindamycin for plasmodium falciparum infections in African children J. Infect. Dis. 2004, 189 (5) 901-908 10.1086/381785
48. Lanaspa, M.; Moraleda, C.; Machevo, S.; González, R.; Serrano, B.; Macete, E.; Cisteró, P.; Mayor, A.; Hutchinson, D.; Kremsner, P. G.; Alonso, P.; Menéndez, C.; Bassat, Q. Inadequate efficacy of a new formulation of Fosmidomycin-clindamycin combination in mozambican children less than three years old with uncomplicated plasmodium falciparum Malaria Antimicrob. Agents Chemother. 2012, 56 (6) 2923-2928 10.1128/AAC.00018-12
49. Soraci, A. L.; Amanto, F.; Tapia, M. O.; de la Torre, E.; Toutain, P.-L. Exposure variability of fosfomycin administered to pigs in food or water: Impact of social rank Res. Vet. Sci. 2014, 96 (1) 153-159 10.1016/j.rvsc.2013.12.003
50. Nemec, A.; Dolzani, L.; Brisse, S.; van den Broek, P.; Dijkshoorn, L. Diversity of aminoglycoside-resistance genes and their association with class 1 integrons among strains of pan-European Acinetobacter baumannii clones J. Med. Microbiol. 2004, 53 (12) 1233-1240 10.1099/jmm.0.45716-0
51. Sizova, I.; Fuhrmann, M.; Hegemann, P. A Streptomyces rimosus aphVIII gene coding for a new type phosphotransferase provides stable antibiotic resistance to Chlamydomonas reinhardtii Gene 2001, 277 (1-2) 221-229 10.1016/S0378-1119(01)00616-3
52. Chopra, I.; Roberts, M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance Microbiol. Mol. Biol. Rev. 2001, 65 (2) 232-260 10.1128/MMBR.65.2.232-260.2001
53. Ghosh, S.; Ramsden, S. J.; LaPara, T. M. The role of anaerobic digestion in controlling the release of tetracycline resistance genes and class 1 integrons from municipal wastewater treatment plants Appl. Microbiol. Biotechnol. 2009, 84 (4) 791-796 10.1007/s00253-009-2125-2
54. Lis, M.; Kuramitsu, H. K. The Stress-responsive dgk gene from Streptococcus mutans encodes a putative undecaprenol kinase activity Infect. Immun. 2003, 71 (4) 1938-1943 10.1128/IAI.71.4.1938-1943.2003
55. Roberts, M. C. Environmental Macrolide-Lincosamide-Streptogramin and Tetracycline resistant bacteria Front. Microbiol. 2011, 2, 40 10.3389/fmicb.2011.00040
56. Perreten, V.; Kadlec, K.; Schwarz, S.; Grönlund Andersson, U.; Finn, M.; Greko, C.; Moodley, A.; Kania, S. A.; Frank, L. A.; Bemis, D. A.; Franco, A.; Iurescia, M.; Battisti, A.; Duim, B.; Wagenaar, J. A.; van Duijkeren, E.; Weese, J. S.; Fitzgerald, J. R.; Rossano, A.; Guardabassi, L. Clonal spread of methicillin-resistant Staphylococcus pseudintermedius in Europe and North America: an international multicentre study J. Antimicrob. Chemother. 2010, 65 (6) 1145-1154 10.1093/jac/dkq078
57. Kobayashi, N.; Nishino, K.; Hirata, T.; Yamaguchi, A. Membrane topology of ABC-type macrolide antibiotic exporter MacB in Escherichia coli FEBS Lett. 2003, 546 (2-3) 241-246 10.1016/S0014-5793(03)00579-9
58. Ter Braak, C. J. F. Canoco: a fortran program for canonical community ordination by (partial) (detrended) (canonical) correspondence analysis, principal components analysis and redundancy analysis, Version 3.1; Agricultural Mathematics Group: Wageningen, 1990.
59. Yang, Y.; Gao, Y.; Wang, S.; Xu, D.; Yu, H.; Wu, L.; Lin, Q.; Hu, Y.; Li, X.; He, Z.; Deng, Y.; Zhou, J. The microbial gene diversity along an elevation gradient of the Tibetan grassland ISME J. 2014, 8 (2) 430-440 10.1038/ismej.2013.146
60. Huang, Z.; Ong, S. L.; Ng, H. Y. Submerged anaerobic membrane bioreactor for low-strength wastewater treatment: Effect of HRT and SRT on treatment performance and membrane fouling Water Res. 2011, 45 (2) 705-713 10.1016/j.watres.2010.08.035
61. Wang, H.; He, Q.; Chen, D.; Wei, L.; Zou, Z.; Zhou, J.; Yang, K.; Zhang, H. Microbial community in a hydrogenotrophic denitrification reactor based on pyrosequencing Appl. Microbiol. Biotechnol. 2015, 99 (24) 10829-10837 10.1007/s00253-015-6929-y
62. Munck, C.; Albertsen, M.; Telke, A.; Ellabaan, M.; Nielsen, P. H.; Sommer, M. O. A. Limited dissemination of the wastewater treatment plant core resistome Nat. Commun. 2015, 6, 8452 10.1038/ncomms9452
63. Sundberg, C.; Al-Soud, W. A.; Larsson, M.; Alm, E.; Yekta, S. S.; Svensson, B. H.; Sørensen, S. J.; Karlsson, A. 454 pyrosequencing analyses of bacterial and archaeal richness in 21 full-scale biogas digesters FEMS Microbiol. Ecol. 2013, 85 (3) 612-626 10.1111/1574-6941.12148
64. Rincón, B.; Borja, R.; González, J. M.; Portillo, M. C.; Sáiz-Jiménez, C. Influence of organic loading rate and hydraulic retention time on the performance, stability and microbial communities of one-stage anaerobic digestion of two-phase olive mill solid residue Biochem. Eng. J. 2008, 40 (2) 253-261 10.1016/j.bej.2007.12.019
65. Delbès, C.; Moletta, R.; Godon, J. J. Bacterial and archaeal 16S rDNA and 16S rRNA dynamics during an acetate crisis in an anaerobic digestor ecosystem FEMS Microbiol. Ecol. 2001, 35 (1) 19-26 10.1016/S0168-6496(00)00107-0
66. Whitehead, R. T.; Cotta, A. M. Sequence analyses of a broad Host-Range plasmid containing ermT from a Tylosin-Resistant Lactobacillus sp. isolated from Swine feces Curr. Microbiol. 2001, 43 (1) 17-20 10.1007/s002840010253
67. Gfeller, K. Y.; Roth, M.; Meile, L.; Teuber, M. Sequence and genetic organization of the 19.3-kb erythromycin- and dalfopristin-resistance plasmid pLME300 from Lactobacillus fermentum ROT1 Plasmid 2003, 50 (3) 190-201 10.1016/j.plasmid.2003.08.001
68. Begovic, J.; Huys, G.; Mayo, B.; D'Haene, K.; Florez, A. B.; Lozo, J.; Kojic, M.; Strahinic, I.; Topisirovic, L. Human vaginal Lactobacillus rhamnosus harbor mutation in 23S rRNA associated with erythromycin resistance Res. Microbiol. 2009, 160 (6) 421-426 10.1016/j.resmic.2009.07.005
69. Ju, F.; Li, B.; Ma, L.; Wang, Y.; Huang, D.; Zhang, T. Antibiotic resistance genes and human bacterial pathogens: Co-occurrence, removal, and enrichment in municipal sewage sludge digesters Water Res. 2016, 91, 1-10 10.1016/j.watres.2015.11.071
70. Pal, C.; Bengtsson-Palme, J.; Kristiansson, E.; Larsson, D. G. J. Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential BMC Genomics 2015, 16, 964 10.1186/s12864-015-2153-5
71. Berg, J.; Tom-Petersen, A.; Nybroe, O. Copper amendment of agricultural soil selects for bacterial antibiotic resistance in the field Lett. Appl. Microbiol. 2005, 40 (2) 146-151 10.1111/j.1472-765X.2004.01650.x
72. Knapp, C. W.; McCluskey, S. M.; Singh, B. K.; Campbell, C. D.; Hudson, G.; Graham, D. W. Antibiotic resistance gene abundances correlate with metal and geochemical conditions in archived Scottish soils PLoS One 2011, 6 (11) e27300 10.1371/journal.pone.0027300
73. Parkhill, J.; Dougan, G.; James, K. D.; Thomson, N. R.; Pickard, D.; Wain, J.; Churcher, C.; Mungall, K. L.; Bentley, S. D.; Holden, M. T. G.; Sebaihia, M.; Baker, S.; Basham, D.; Brooks, K.; Chillingworth, T.; Connerton, P.; Cronin, A.; Davis, P.; Davies, R. M.; Dowd, L.; White, N.; Farrar, J.; Feltwell, T.; Hamlin, N.; Haque, A.; Hien, T. T.; Holroyd, S.; Jagels, K.; Krogh, A.; Larsen, T. S.; Leather, S.; Moule, S.; O'Gaora, P.; Parry, C.; Quail, M.; Rutherford, K.; Simmonds, M.; Skelton, J.; Stevens, K.; Whitehead, S.; Barrell, B. G. Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18 Nature 2001, 413 (6858) 848-852 10.1038/35101607
74. Perron, K.; Caille, O.; Rossier, C.; van Delden, C.; Dumas, J.-L.; Köhler, T. CzcR-CzcS, a Two-component system involved in heavy metal and carbapenem resistance in Pseudomonas aeruginosa J. Biol. Chem. 2004, 279 (10) 8761-8768 10.1074/jbc.M312080200
75. Hu, Q.; Zhang, X.-X.; Jia, S.; Huang, K.; Tang, J.; Shi, P.; Ye, L.; Ren, H. Metagenomic insights into ultraviolet disinfection effects on antibiotic resistome in biologically treated wastewater Water Res. 2016, 101, 309-317 10.1016/j.watres.2016.05.092