Abstract
NDM-1 (New Delhi metallo-beta-lactamase) gene encodes a metallo-beta-lactamase (MBL) with high carbapenemase activity, which makes the host bacterial strain easily dispatch the last-resort antibiotics known as carbapenems and cause global concern. Here we present the bioinformatics data showing an unexpected similarity between NDM-1 and beta-lactamase II from Erythrobacter litoralis, a marine microbial isolate. We have further expressed these two mature proteins in E. coli cells, both of which present as a monomer with a molecular mass of 25 kDa. Antimicrobial susceptibility assay reveals that they share similar substrate specificities and are sensitive to aztreonam and tigecycline. The conformational change accompanied with the zinc binding visualized by nuclear magnetic resonance, Zn2+-bound NDM-1, adopts at least some stable tertiary structure in contrast to the metal-free protein. Our work implies a close evolutionary relationship between antibiotic resistance genes in environmental reservoir and in the clinic, challenging the antimicrobial resistance monitoring.
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Allen, H.K., Donato, J., Wang, H.H., Cloud-Hansen, K.A., Davies, J., and Handelsman, J. (2010). Call of the wild: antibiotic resistance genes in natural environments. Nat Rev Microbiol 8, 251–259.
Benson, D.A., Karsch-Mizrachi, I., Lipman, D.J., Ostell, J., and Sayers, E.W. (2010). GenBank. Nucleic Acids Res 38, D46–D51.
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.
Bonten, M.J., Willems, R., and Weinstein, R.A. (2001). Vancomycinresistant enterococci: why are they here, and where do they come from? Lancet Infect Dis 1, 314–325.
Bush, K. (2010). Alarming β-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae. Curr Opin Microbiol 13, 558–564.
Crawford, P.A., Yang, K.W., Sharma, N., Bennett, B., and Crowder, M.W. (2005). Spectroscopic studies on cobalt(II)-substituted metallo-beta-lactamase ImiS from Aeromonas veronii bv. sobria. Biochemistry 44, 5168–5176.
D’Costa, V.M., McGrann, K.M., Hughes, D.W., and Wright, G.D. (2006). Sampling the antibiotic resistome. Science 311, 374–377.
Fudou, R., Jojima, Y., Iizuka, T., and Yamanaka, S. (2002). Haliangium ochraceum gen. nov., sp. nov. and Haliangium tepidum sp. nov.: novel moderately halophilic myxobacteria isolated from coastal saline environments. J Gen Appl Microbiol 48, 109–116.
Hehemann, J.H., Correc, G., Barbeyron, T., Helbert, W., Czjzek, M., and Michel, G. (2010). Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464, 908–912.
Hu, Z., Gunasekera, T. S., Spadafora, L., Bennett, B., and Crowder, M.W. (2008). Metal content of metallo-beta-lactamase L1 is determined by the bioavailability of metal ions. Biochemistry 47, 7947–7953.
Hu, Z., Periyannan, G., Bennett, B., and Crowder, M.W. (2008). Role of the Zn1 and Zn2 sites in metallo-beta-lactamase L1. J Am Chem Soc 130, 14207–14216.
Huo, T.I. (2010). The first case of multidrug-resistant NDM-1-harboring Enterobacteriaceae in Taiwan: here comes the superbacteria! J Chin Med Assoc 73, 557–558.
Hutchings, M.I., Palmer, T., Harrington, D.J., and Sutcliffe, I.C. (2009). Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold’ em, knowing when to fold’ em. Trends Microbiol 17, 13–21.
Kumarasamy, K.K., Toleman, M.A., Walsh, T.R., Bagaria, J., Butt, F., Balakrishnan, R., Chaudhary, U., Doumith, M., Giske, C.G., Irfan, S., et al. (2010). Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 10, 597–602.
Levy, S.B., and Marshall, B. (2004). Antibacterial resistance worldwide: causes, challenges and responses. Nat Med 10, S122–S129.
Marshall, C.G., Broadhead, G., Leskiw, B.K., and Wright, G.D. (1997). D-Ala-D-Ala ligases from glycopeptide antibioticproducing organisms are highly homologous to the enterococcal vancomycin-resistance ligases VanA and VanB. Proc Natl Acad Sci U S A 94, 6480–6483.
Martínez, J.L. (2008). AAntibiotics and antibiotic resistance genes in natural environments. Science 321, 365–367.
Martínez, J.L., Baquero, F., and Andersson, D.I. (2007). Predicting antibiotic resistance. Nat Rev Microbiol 5, 958–965.
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.
Moellering, R.C. Jr. (2010). NDM-1—a cause for worldwide concern. N Engl J Med 363, 2377–2379.
Oh, H.M., Giovannoni, S.J., Ferriera, S., Johnson, J., and Cho, J.C. (2009). Complete genome sequence of Erythrobacter litoralis HTCC2594. J Bacteriol 191, 2419–2420.
Periyannan, G.R., Costello, A.L., Tierney, D.L., Yang, K.W., Bennett, B., and Crowder, M.W. (2006). Sequential binding of cobalt(II) to metallo-beta-lactamase CcrA. Biochemistry 45, 1313–1320.
Poirel, L., Al Maskari, Z., Al Rashdi, F., Bernabeu, S., and Nordmann, P. (2011a). NDM-1-producing Klebsiella pneumoniae isolated in the Sultanate of Oman. J Antimicrob Chemother 66, 304–306
Poirel, L., Héritier, C., and Nordmann, P. (2005). Genetic and biochemical characterization of the chromosome-encoded class B beta-lactamases from Shewanella livingstonensis (SLB-1) and Shewanella frigidimarina (SFB-1). J Antimicrob Chemother 55, 680–685.
Poirel, L., Kämpfer, P., and Nordmann, P. (2002). Chromosomeencoded Ambler class A beta-lactamase of Kluyvera georgiana, a probable progenitor of a subgroup of CTX-M extended-spectrum beta-lactamases. Antimicrob Agents Chemother 46, 4038–4040.
Poirel, L., Lagrutta, E., Taylor, P., Pham, J., and Nordmann, P. (2010). Emergence of metallo-β-lactamase NDM-1-producing multidrugresistant Escherichia coli in Australia. Antimicrob Agents Chemother 54, 4914–4916.
Poirel, L., Revathi, G., Bernabeu, S., and Nordmann, P. (2011b). Detection of NDM-1-producing Klebsiella pneumoniae in Kenya. Antimicrob Agents Chemother 55, 934–936
Poirel, L., Ros, A., Carricajo, A., Berthelot, P., Pozzetto, B., Bernabeu, S., and Nordmann, P. (2011c). Extremely drug-resistant Citrobacter freundii identified in a patient returning from India and producing NDM-1 and other carbapenemases. Antimicrob Agents Chemother 55, 447–448.
Rolain, J.M., Parola, P., and Cornaglia, G. (2010). New Delhi metallobeta-lactamase (NDM-1): towards a new pandemia? Clin Microbiol Infect 12, 1699–1701.
Samuelsen, O., Thilesen, C.M., Heggelund, L., Vada, A.N., Kummel, A., and Sundsfjord, A. (2011). Identification of NDM-1-producing Enterobacteriaceae in Norway. J Antimicrob Chemother 66, 670–672.
Schlesner, H., Bartels, C., Sittig, M., Dorsch, M., and Stackebrandt, E. (1990). Taxonomic and phylogenetic studies on a new taxon of budding, hyphal Proteobacteria, Hirschia baltica gen. nov., sp. nov. Int J Syst Bacteriol 40, 443–451.
Scrofani, S.D., Chung, J., Huntley, J.J., Benkovic, S.J., Wright, P.E., and Dyson, H.J. (1999). NMR characterization of the metallo-betalactamase from Bacteroides fragilis and its interaction with a tightbinding inhibitor: role of an active-site loop. Biochemistry 38, 14507–14514.
Toth, M., Smith, C., Frase, H., Mobashery, S., and Vakulenko, S. (2010). An antibiotic-resistance enzyme from a deep-sea bacterium. J Am Chem Soc 132, 816–823.
Walsh, T.R. (2010). Emerging carbapenemases: a global perspective. Int J Antimicrob Agents 36, S8–S14.
Wright, G.D. (2007). The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev Microbiol 5, 175–186.
Wright, G.D. (2010). Antibiotic resistance in the environment: a link to the clinic? Curr Opin Microbiol 13, 589–594.
Yong, D., Toleman, M.A., Giske, C.G., Cho, H.S., Sundman, K., Lee, K., and Walsh, T.R. (2009). Characterization of a new metallo-betalactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 53, 5046–5054.
Zhang, X. (2010). Human in check: new threat from superbugs equipped with NDM-1. Protein Cell 1, 1051–1052.
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Zheng, B., Tan, S., Gao, J. et al. An unexpected similarity between antibiotic-resistant NDM-1 and beta-lactamase II from Erythrobacter litoralis. Protein Cell 2, 250–258 (2011). https://doi.org/10.1007/s13238-011-1027-0
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DOI: https://doi.org/10.1007/s13238-011-1027-0