S.Yadry.A Kapley Science of the Totat t62(20191155-1164 1n6回 Jadeja N.B.M alar mech. o20159ni ale.H.Sa LA. V-ctaL2 (MEG)S che AddsW-W iotic resistance in India:drivers and ono L2016 0y50.6670-667 overy.Biochem.Pharmacol.134 organisms as a souro 及C201Me iA-D 13 .2081 2 Pilla.G. he fu very:80 vea x-M.Sha CM.R 2013.The last 0te499394 ForbesJD.KmoxN.C.Ro Pagot etagenomics:the next vak.IT. 10 e13.40 2016 05 13. acid pro by Streptomyces clavuligerus:biogenesi Water Res.123 468-4Berglund, B., 2015. Environmental dissemination of antibiotic resistance genes and corre￾lation to anthropogenic contamination with antibiotics. Infection Ecology & Epidemi￾ology 5. https://doi.org/10.3402/iee.v5.28564. Bernard, G., Pathmanathan, J.S., Lannes, R., Lopez, P., Bapteste, E., 2018. Microbial dark matter investigations: how microbial studies transform biological knowledge and empirically sketch a logic of scientific discovery. Genome biology and evolution 10, 707–715. Blair, J.M.A., Webber, M.A., Baylay, A.J., Ogbolu, D.O., Piddock, L.J.V., 2015. Molecular mech￾anisms of antibiotic resistance. Nat Rev Micro 13, 42–51. Blankenfeldt, W., Parsons, J.F., 2014. The structural biology of phenazine biosynthesis. Curr. Opin. Struct. Biol. 29, 26–33. Brown, E.D., Wright, G.D., 2016. Antibacterial drug discovery in the resistance era. Nature 529, 336–343. Brunton, L.A., Desbois, A.P., Garza, M., Wieland, B., Mohan, C.V., Häsler, B., et al., 2019. Identifying hotspots for antibiotic resistance emergence and selection, and elucidat￾ing pathways to human exposure: application of a systems-thinking approach to aquaculture systems. Sci. Total Environ. 687, 1344–1356. Cai, M., Wilkins, D., Chen, J., Ng, S.K., Lu, H., Jia, Y., et al., 2016. Metagenomic reconstruction of key anaerobic digestion pathways in municipal sludge and industrial wastewater biogas-producing systems. Front. Microbiol. 7, 778. Castro, A.P., Fernandes, G.D.R., Franco, O.L., 2014. Insights into novel antimicrobial com￾pounds and antibiotic resistance genes from soil metagenomes. Front. Microbiol. 5, 489. Che, Y., Xia, Y., Liu, L., Li, A.-D., Yang, Y., Zhang, T., 2019. Mobile antibiotic resistome in wastewater treatment plants revealed by Nanopore metagenomic sequencing. Microbiome 7, 44. Chen, B., Yuan, K., Chen, X., Yang, Y., Zhang, T., Wang, Y., et al., 2016. Metagenomic anal￾ysis revealing antibiotic resistance genes (ARGs) and their genetic compartments in the Tibetan environment. Environmental Science & Technology 50, 6670–6679. Clausen, P.T.L.C., Zankari, E., Aarestrup, F.M., Lund, O., 2016. Benchmarking of methods for identification of antimicrobial resistance genes in bacterial whole genome data. J. Antimicrob. Chemother. 71, 2484–2488. Crits-Christoph, A., Diamond, S., Butterfield, C.N., Thomas, B.C., Banfield, J.F., 2018. Novel soil bacteria possess diverse genes for secondary metabolite biosynthesis. Nature 558, 440. Culligan, E.P., Sleator, R.D., Marchesi, J.R., Hill, C., 2014. Metagenomics and novel gene dis￾covery: promise and potential for novel therapeutics. Virulence 5, 399–412. Dang, B.N., Graham, D.Y., 2017. Helicobacter pylori infection and antibiotic resistance: a WHO high priority? Nat. Rev. Gastroenterol. Hepatol. 14, 383. Das, S., Choudhry, S., Saha, R., Ramachandran, V.G., Kaur, K., Sarkar, B.L., 2011. Emergence of multiple drug resistance Vibrio cholerae O1 in East Delhi. J Infect Dev Ctries 5, 294–298. Demain, A.L., Sanchez, S., 2009. Microbial drug discovery: 80 years of progress. J Antibiot 62, 5–16. dos Santos, D.F.K., Istvan, P., Quirino, B.F., Kruger, R.H., 2017. Functional metagenomics as a tool for identification of new antibiotic resistance genes from natural environments. Microb. Ecol. 73, 479–491. Du, Y.-L., Shen, X.-L., Yu, P., Bai, L.-Q., Li, Y.-Q., 2011. Gamma-butyrolactone regulatory sys￾tem of Streptomyces chattanoogensis links nutrient utilization, metabolism, and de￾velopment. Appl. Environ. Microbiol. 77, 8415–8426. Finley, R.L., Collignon, P., Larsson, D.G.J., McEwen, S.A., Li, X.-Z., Gaze, W.H., et al., 2013. The scourge of antibiotic resistance: the important role of the environment. Clin. Infect. Dis. 57, 704–710. Fluegge, K., 2017. A novel host-pathogen interaction potentially driving antibiotic resis￾tance in livestock feedlots. Environ. Sci. Pollut. Res. Int. 24, 12501. Forbes, J.D., Knox, N.C., Ronholm, J., Pagotto, F., Reimer, A., 2017. Metagenomics: the next culture-independent game changer. Front. Microbiol. 8, 1069. Founou, R.C., Founou, L.L., Essack, S.Y., 2017. Clinical and economic impact of antibiotic re￾sistance in developing countries: a systematic review and meta-analysis. PLoS One 12, e0189621. Fuente-Núñez, C., Reffuveille, F., Haney, E.F., Straus, S.K., Hancock, R.E.W., 2014. Broad￾spectrum anti-biofilm peptide that targets a cellular stress response. PLoS Pathog. 10, e1004152. Gatica, J., Jurkevitch, E., Cytryn, E., 2019. Comparative metagenomics and network analy￾ses provide novel insights into the scope and distribution of β-lactamase homologs in the environment. Front. Microbiol. 10. Göttig, S., Gruber, T.M., Higgins, P.G., Wachsmuth, M., Seifert, H., Kempf, V.A.J., 2014. De￾tection of pan drug-resistant Acinetobacter baumannii in Germany. J. Antimicrob. Chemother. 69, 2578–2579. Gullberg, E., Albrecht, L.M., Karlsson, C., Sandegren, L., Andersson, D.I., 2014. Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals. MBio 5 (e01918-14). Guo, J., Li, J., Chen, H., Bond, P.L., Yuan, Z., 2017. Metagenomic analysis reveals wastewater treatment plants as hotspots of antibiotic resistance genes and mobile genetic ele￾ments. Water Res. 123, 468–478. He, L.-Y., He, L.-K., Liu, Y.-S., Zhang, M., Zhao, J.-L., Zhang, Q.-Q., et al., 2019. Microbial di￾versity and antibiotic resistome in swine farm environments. Sci. Total Environ. 685, 197–207. Hofer, U., 2019. The cost of antimicrobial resistance. Nat Rev Microbiol 17, 3. Holmes, A.H., Moore, L.S., Sundsfjord, A., Steinbakk, M., Regmi, S., Karkey, A., et al., 2016. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 387, 176–187. Huijbers, P.M.C., Blaak, H., de Jong, M.C.M., Graat, E.A.M., Vandenbroucke-Grauls, C.M.J.E., de Roda Husman, A.M., 2015. Role of the environment in the transmission of antimi￾crobial resistance to humans: a review. Environmental Science & Technology 49, 11993–12004. Jadeja, N.B., More, R.P., Purohit, H.J., Kapley, A., 2014. Metagenomic analysis of oxygenases from activated sludge. Bioresour. Technol. 165, 250–256. Jadeja, N.B., Purohit, H.J., Kapley, A., 2019. Decoding microbial community intelligence through metagenomics for efficient wastewater treatment. Functional & Integrative Genomics 1–13. Jelic, A., Gros, M., Ginebreda, A., Cespedes-Sánchez, R., Ventura, F., Petrovic, M., et al., 2011. Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during wastewater treatment. Water Res. 45, 1165–1176. Kapley, A., Liu, R., Jadeja, N.B., Zhang, Y., Yang, M., Purohit, H.J., 2015. Shifts in microbial community and its correlation with degradative efficiency in a wastewater treatment plant. Appl. Biochem. Biotechnol. 176, 2131–2143. Kapley, A., Tanksale, H., Sagarkar, S., Prasad, A.R., Kumar, R.A., Sharma, N., et al., 2016. An￾timicrobial activity of Alcaligenes sp. HPC 1271 against multidrug resistant bacteria. Functional & integrative genomics 16, 57–65. Karkman, A., Do, T.T., Walsh, F., Virta, M.P.J., 2017. Antibiotic-resistance genes in waste water. Trends Microbiol. 26, 220–228. Keegan, K.P., Glass, E.M., Meyer, F., 2016. MG-RAST, a metagenomics service for analysis of microbial community structure and function. Microbial Environmental Genomics (MEG). Springer, pp. 207–233. Klumper, U., Riber, L., Dechesne, A., Sannazzarro, A., Hansen, L.H., Sorensen, S.J., et al., 2015. Broad host range plasmids can invade an unexpectedly diverse fraction of a soil bacterial community. ISME J 9, 934–945. Laczny, C.C., Kiefer, C., Galata, V., Fehlmann, T., Backes, C., Keller, A., 2017. BusyBee Web: metagenomic data analysis by bootstrapped supervised binning and annotation. Nucleic Acids Res. 45, W171–W179. Laxminarayan, R., Chaudhury, R.R., 2016. Antibiotic resistance in India: drivers and oppor￾tunities for action. PLoS Med. 13, e1001974. Lewis, J.D., Chen, E.Z., Baldassano, R.N., Otley, A.R., Griffiths, A.M., Lee, D., 2015. Inflamma￾tion, antibiotics, and diet as environmental stressors of the gut microbiome in pediat￾ric Crohn's disease. Cell Host Microbe 18, 489–500. Lewis, K., 2017. New approaches to antimicrobial discovery. Biochem. Pharmacol. 134, 87–98. Lewis, K., Epstein, S., D'Onofrio, A., Ling, L.L., 2010. Uncultured microorganisms as a source of secondary metabolites. J Antibiot 63, 468–476. Li, A.-D., Li, L.-G., Zhang, T., 2015. Exploring antibiotic resistance genes and metal resis￾tance genes in plasmid metagenomes from wastewater treatment plants. Front. Microbiol. 6, 1025. Liu, Y., Yang, D., Zhang, N., Chen, L., Cui, Z., Shen, Q., et al., 2016. Characterization of uncul￾tured genome fragment from soil metagenomic library exposed rare mismatch of in￾ternal tetranucleotide frequency. Front. Microbiol. 7, 2081. Lobanovska, M., Pilla, G., 2017. Penicillin's discovery and antibiotic resistance: lessons for the future? The Yale Journal of Biology and Medicine 90, 135–145. Luo, G., Li, B., Li, L.-G., Zhang, T., Angelidaki, I., 2017. Antibiotic resistance genes and corre￾lations with microbial community and metal resistance genes in full-scale biogas re￾actors as revealed by metagenomic analysis. Environmental Science & Technology 51, 4069–4080. Lv, X.-M., Shao, M.-F., Li, J., Li, C.-L., 2015. Metagenomic analysis of the sludge microbial community in a lab-scale denitrifying phosphorus removal reactor. Appl. Biochem. Biotechnol. 175, 3258–3270. Manaia, C.M., Rocha, J., Scaccia, N., Marano, R., Radu, E., Biancullo, F., et al., 2018. Antibiotic resistance in wastewater treatment plants: tackling the black box. Environ. Int. 115, 312–324. McKenna, M., 2013. The last resort. Nature 499, 394. Melnyk, A.H., Wong, A., Kassen, R., 2015. The fitness costs of antibiotic resistance muta￾tions. Evolutionary applications 8, 273–283. Miller, J.H., Novak, J.T., Knocke, W.R., Pruden, A., 2016. Survival of antibiotic resistant bac￾teria and horizontal gene transfer control antibiotic resistance gene content in anaer￾obic digesters. Front. Microbiol. 7, 263. Nnadozie, C., Kumari, S., Bux, F., 2017. Status of pathogens, antibiotic resistance genes and antibiotic residues in wastewater treatment systems. Rev. Environ. Sci. Biotechnol. 16, 491–515. Nowrotek, M., Jałowiecki, Ł., Harnisz, M., Płaza, G.A., 2019. Culturomics and metagenomics: in understanding of environmental resistome. Frontiers of Environ￾mental Science & Engineering 13, 40. Osińska, A., Harnisz, M., Korzeniewska, E., 2016. Prevalence of plasmid-mediated multidrug resistance determinants in fluoroquinolone-resistant bacteria iso￾lated from sewage and surface water. Environ. Sci. Pollut. Res. Int. 23, 10818–10831. Pal, C., Bengtsson-Palme, J., Kristiansson, E., Larsson, D.G.J., 2015. Co-occurrence of resis￾tance genes to antibiotics, biocides and metals reveals novel insights into their co￾selection potential. BMC Genomics 16, 964. Paradkar, A., 2013. Clavulanic acid production by Streptomyces clavuligerus: biogenesis, regulation and strain improvement. J Antibiot 66, 411–420. Parks, D.H., Tyson, G.W., Hugenholtz, P., Beiko, R.G., 2014. STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics 30, 3123–3124. Pierson, L.S., Pierson, E.A., 2010. Metabolism and function of phenazines in bacteria: im￾pacts on the behavior of bacteria in the environment and biotechnological processes. Appl. Microbiol. Biotechnol. 86, 1659–1670. Raina, V., Panda, A.N., Mishra, S.R., Nayak, T., Suar, M., 2019. Microbial biodiversity study of a brackish water ecosystem in eastern India: The Chilika Lake. Microbial Diversity in the Genomic Era. Elsevier, pp. 47–63. Reddy, B., Dubey, S.K., 2019. River Ganges water as reservoir of microbes with antibiotic and metal ion resistance genes: high throughput metagenomic approach. Environ. Pollut. 246, 443–451. Seemann, T., 2014. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069. S. Yadav, A. Kapley / Science of the Total Environment 692 (2019) 1155–1164 1163