A new member of the class metallo-β-lactamase (MBL), New Delhi metallo-beta-lactamase 1 (NDM-1) has emerged recently as a leading threat to the treatment of infections that have spread in all major Gram-negative pathogens. The enzyme inactivates antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections. This review provides information about NDM-1 spatial structure, potential features of the active site, and its mechanism of action. It also enlists the inhibitors/compounds/drugs against NDM-1 in various development phases. Understanding their mode of inhibition and the structure-activity relationship would be beneficial for development, synthesis, and even increasing biological efficacy of inhibitors, making them more promising drug candidates.
Get full access to this article
View all access options for this article.
References
1.
TacconelliE., MagriniN., KahlmeterG., and SinghN.. 2017. Global Priority List of Antibiotic-Resistant Bacteria to Guide Research. Discovery, and Development of New Antibiotics. WHO, Geneva.
2.
Centers for Diseases Control and Prevention (CDC). 2013. Antibiotic resistance threats in the United States. Available at www.cdc.gov/drugresistance/threat-report-2013 (last accessed April29, 2020).
3.
BushK.2013. The ABCD's of β-lactamase nomenclature. J. Infect. Chemother. 19:549–559.
4.
BushK., and BradfordP.A.. 2016. β-Lactams and β-lactamase inhibitors: an overview. Cold Spring Harb. Perspect. Med. 6:a025247.
5.
BebroneC.2007. Metallo-β-lactamases (classification, activity, genetic organization, structure, zinc coordination) and their superfamily. Biochem. Pharmacol. 74:1686–1701.
6.
MojicaM.F., BonomoR.A., and FastW.. 2016. B1-metallo-β-lactamases: where do we stand? Curr. Drug Targets, 17:1029–1050.
7.
Yong, D., M.A. Toleman, C.G. Giske, H.S. Cho, K. Sundman, K. Lee, and T.R. Walsh. 2009. Characterization of a new metallo-β-lactamase gene, blaNDM-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.
8.
DrawzS.M., and BonomoR.A.. 2010. Three decades of β-lactamase inhibitors. Clin. Microbiol. Rev. 23:160–201.
9.
TijetN., BoydD., PatelS.N., MulveyM.R., and MelanoR.G.. 2013. Evaluation of the Carba NP test for rapid detection of carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 57:4578–4580.
10.
WangJ., LiY., YanH., DuanJ., LuoX., FengX., LuL., and WangW.. 2018. Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli. RSC Adv. 8:5936–5944.
11.
LahiriS.D., ManganiS., Durand-RevilleT., BenvenutiM., De LucaF., SanyalG., and DocquierJ.-D.. 2013. Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC β-lactamases. Antimicrob. Agents Chemother. 57:2496–2505.
12.
BushnellG., Mitrani-GoldF., and MundyL.M.. 2013. Emergence of New Delhi metallo-β-lactamase type 1-producing Enterobacteriaceae and non-Enterobacteriaceae: global case detection and bacterial surveillance. Int. J. Infect. Dis. 17:e325–e333.
13.
GrundmannH., LivermoreD., GiskeC., CantonR., RossoliniG., CamposJ., VatopoulosA., GniadkowskiM., TothA., and PfeiferY.. 2010. Carbapenem-non-susceptible Enterobacteriaceae in Europe: conclusions from a meeting of national experts. Eurosurveillance. 15:1–13.
14.
KarthikeyanK., ThirunarayanM., and KrishnanP.. 2010. Coexistence of bla OXA-23 with bla NDM-1 and armA in clinical isolates of Acinetobacter baumannii from India. J. Antimicrob. Chemother. 65:2253–2254.
15.
WalshT.R., WeeksJ., LivermoreD.M., and TolemanM.A.. 2011. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. Lancet Infect. Dis. 11:355–362.
16.
GuoY., WangJ., NiuG., ShuiW., SunY., ZhouH., ZhangY., YangC., LouZ., and RaoZ.. 2011. A structural view of the antibiotic degradation enzyme NDM-1 from a superbug. Protein Cell, 2:384–394.
17.
Garcia-SaezI., DocquierJ.-D., RossoliniG., and DidebergO.. 2008. The three-dimensional structure of VIM-2, a Zn-β-lactamase from Pseudomonas aeruginosa in its reduced and oxidised form. J. Mol. Biol. 375:604–611.
18.
ConchaN.O., JansonC.A., RowlingP., PearsonS., CheeverC.A., ClarkeB.P., LewisC., GalleniM., FrereJ.-M., and PayneD.J.. 2000. Crystal structure of the IMP-1 metallo β-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor: binding determinants of a potent, broad-spectrum inhibitor. Biochemistry, 39:4288–4298.
19.
MoaliC., AnneC., Lamotte-BrasseurJ., GroslambertS., DevreeseB., Van BeeumenJ., GalleniM., and FrèreJ.-M.. 2003. Analysis of the importance of the metallo-β-lactamase active site loop in substrate binding and catalysis. Chem. Biol. 10:319–329.
20.
MeiniM.-R., LlarrullL., and VilaA.. 2014. Evolution of metallo-β-lactamases: trends revealed by natural diversity and in vitro evolution. Antibiotics, 3:285–316.
21.
ChenJ., ChenH., ShiY., HuF., LaoX., GaoX., ZhengH., and YaoW.. 2013. Probing the effect of the non-active-site mutation Y229W in New Delhi metallo-β-lactamase-1 by site-directed mutagenesis, kinetic studies, and molecular dynamics simulations. PLoS One, 8:e82080.
22.
GonzálezJ.M., BuschiazzoA., and VilaA.J.. 2010. Evidence of adaptability in metal coordination geometry and active-site loop conformation among B1 metallo-β-lactamases. Biochemistry, 49:7930–7938.
23.
HoS.N., HuntH.D., HortonR.M., PullenJ.K., and PeaseL.R.. 1989. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene, 77:51–59.
24.
MarcocciaF., LeirosH.-K.S., AschiM., AmicosanteG., and PerilliM.. 2018. Exploring the role of L209 residue in the active site of NDM-1 a metallo-β-lactamase. PLoS One, 13:e0189686.
25.
BuggT., and WalshC.. 1992. Intracellular steps of bacterial cell wall peptidoglycan biosynthesis: enzymology, antibiotics, and antibiotic resistance. Nat. Prod. Rep. 9:199–215.
26.
KellyJ., KuzinA., CharlierP., and FonzeE.. 1998. X-ray studies of enzymes that interact with penicillins. Cell. Mol. Life Sci. 54:353–358.
27.
MassovaI., and MobasheryS.. 1998. Kinship and diversification of bacterial penicillin-binding proteins and β-lactamases. Antimicrob. Agents Chemother. 42:1–17.
28.
Ghuysen, J.-M. 1997. Penicillin-binding proteins. Wall peptidoglycan assembly and resistance to penicillin: facts, doubts and hopes. Int. J. Antimicrob. Agents, 8:45–60.
29.
LeeW., McDonoughM.A., KotraL.P., LiZ.-H., SilvaggiN.R., TakedaY., KellyJ.A., and MobasheryS.. 2001. A 1.2-Å snapshot of the final step of bacterial cell wall biosynthesis. Proc. Natl. Acad. Sci. U. S. A. 98:1427–1431.
30.
TipperD.J., and StromingerJ.L.. 1965. Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc. Natl. Acad. Sci. U. S. A. 54:1133–1141.
31.
KuzinA.P., LiuH., KellyJ.A., and KnoxJ.R.. 1995. Binding of cephalothin and cefotaxime to D-Ala-D-Ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases. Biochemistry, 34:9532–9540.
32.
Buynak, J.D. 2007. Cutting and stitching: the cross-linking of peptidoglycan in the assembly of the bacterial cell wall. ACS Chem. Biol. 2:602–605.
33.
ShiQ., MerouehS.O., FisherJ.F., and MobasheryS.. 2011. A computational evaluation of the mechanism of penicillin-binding protein-catalyzed cross-linking of the bacterial cell wall. J. Am. Chem. Soc. 133:5274–5283.
34.
MeiniM.-R., LlarrullL.I., and VilaA.J.. 2015. Overcoming differences: the catalytic mechanism of metallo-β-lactamases. FEBS Lett. 589:3419–3432.
35.
GroundwaterP.W., XuS., LaiF., VáradiL., TanJ., PerryJ.D., and HibbsD.E.. 2016. New Delhi metallo-β-lactamase-1: structure, inhibitors and detection of producers. Future Med. Chem. 8:993–1012.
36.
KhanA.U., MaryamL., and ZarrilliR.. 2017. Structure, genetics and worldwide spread of New Delhi metallo-β-lactamase (NDM): a threat to public health. BMC Microbiol. 17:101.
37.
KingD.T., and StrynadkaN.C.. 2013. Targeting metallo-β-lactamase enzymes in antibiotic resistance. Future Med. Chem. 5:1243–1263.
38.
FastW., and SuttonL.D.. 2013. Metallo-β-lactamase: inhibitors and reporter substrates. Biochim. Biophys. Acta Proteins Proteomics, 1834:1648–1659.
39.
Papp-WallaceK.M., EndimianiA., TaracilaM.A., and BonomoR.A.. 2011. Carbapenems: past, present, and future. Antimicrob. Agents Chemother. 55:4943–4960.
40.
ZhangH., and HaoQ.. 2011. Crystal structure of NDM-1 reveals a common β-lactam hydrolysis mechanism. FASEB J. 25:2574–2582.
41.
ZhuK., LuJ., LiangZ., KongX., YeF., JinL., GengH., ChenY., ZhengM., and JiangH.. 2013. A quantum mechanics/molecular mechanics study on the hydrolysis mechanism of New Delhi metallo-β-lactamase-1. J. Comput. Aided Mol. Des. 27:247–256.
42.
TripathiR., and NairN.N.. 2015. Mechanism of meropenem hydrolysis by New Delhi metallo β-lactamase. ACS Catal. 5:2577–2586.
43.
KimY., CunninghamM.A., MireJ., TesarC., SacchettiniJ., and JoachimiakA.. 2013. NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism. FASEB J. 27:1917–1927.
44.
KingD.T., WorrallL.J., GruningerR., and StrynadkaN.C.. 2012. New Delhi metallo-β-lactamase: structural insights into β-lactam recognition and inhibition. J. Am. Chem. Soc. 134:11362–11365.
45.
YangH., AithaM., MartsA.R., HetrickA., BennettB., CrowderM.W., and TierneyD.L.. 2014. Spectroscopic and mechanistic studies of heterodimetallic forms of metallo-β-lactamase NDM-1. J. Am. Chem. Soc. 136:7273–7285.
46.
WangZ., FastW., and BenkovicS.J.. 1999. On the mechanism of the metallo-β-lactamase from Bacteroides fragilis. Biochemistry, 38:10013–10023.
47.
TaibiP., and MobasheryS.. 1995. Mechanism of turnover of imipenem by the TEM beta-lactamase revisited. J. Am. Chem. Soc. 117:7600–7605.
48.
TioniM.F., LlarrullL.I., Poeylaut-PalenaA.A., MartíM.A., SagguM., PeriyannanG.R., MataE.G., BennettB., MurgidaD.H., and VilaA.J.. 2008. Trapping and characterization of a reaction intermediate in carbapenem hydrolysis by B. cereus metallo-β-lactamase. J. Am. Chem. Soc. 130:15852–15863.
49.
SchneiderK.D., KarpenM.E., BonomoR.A., LeonardD.A., and PowersR.A.. 2009. The 1.4 Å crystal structure of the class D β-lactamase OXA-1 complexed with doripenem. Biochemistry, 48:11840–11847.
50.
FonsecaF.T., ChudykE.I., van der KampM.W., CorreiaA.N., MulhollandA.J., and SpencerJ.. 2012. The basis for carbapenem hydrolysis by class A β-lactamases: a combined investigation using crystallography and simulations. J. Am. Chem. Soc. 134:18275–18285.
51.
FengH., LiuX., WangS., FlemingJ., WangD.-C., and LiuW.. 2017. The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis. Nat. Commun. 8:2242.
52.
AokiN., IshiiY., TatedaK., SagaT., KimuraS., KikuchiY., KobayashiT., TanabeY., TsukadaH., and GejyoF.. 2010. Efficacy of calcium-EDTA as an inhibitor for metallo-β-lactamase in a mouse model of Pseudomonas aeruginosa pneumonia. Antimicrob. Agents Chemother. 54:4582–4588.
53.
YoshizumiA., IshiiY., LivermoreD.M., WoodfordN., KimuraS., SagaT., HaradaS., YamaguchiK., and TatedaK.. 2013. Efficacies of calcium–EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 β-lactamase. J. Infect. Chemother. 19:992–995.
54.
KingA.M., Reid-YuS.A., WangW., KingD.T., De PascaleG., StrynadkaN.C., WalshT.R., CoombesB.K., and WrightG.D.. 2014. Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance. Nature, 510:503.
55.
BremJ., CainR., CahillS., McDonoughM.A., CliftonI.J., Jiménez-CastellanosJ.-C., AvisonM.B., SpencerJ., FishwickC.W., and SchofieldC.J.. 2016. Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates. Nat. Commun. 7:12406.
56.
BüttnerD., KramerJ.S., KlinglerF.-M., WittmannS.K., HartmannM.R., KurzC.G., KohnhäuserD., WeizelL., BrüggerhoffA., and FrankD.. 2017. Challenges in the development of a thiol-based broad-spectrum inhibitor for metallo-β-lactamases. ACS Infect. Dis. 4:360–372.
57.
ThomasP.W., CammarataM., BrodbeltJ.S., and FastW.. 2014. Covalent inhibition of New Delhi metallo-β-lactamase-1 (NDM-1) by cefaclor. ChemBioChem, 15:2541–2548.
58.
ChristopeitT., AlbertA., and LeirosH.-K.S.. 2016. Discovery of a novel covalent non-β-lactam inhibitor of the metallo-β-lactamase NDM-1. Bioorg. Med. Chem. 24:2947–2953.
59.
HamrickJ.-C., DocquierJ.-D., UeharaT., MyersC.-L., SixD.-A., ChatwinC.-L., JohnK.-J., VernacchioS.-F., CusickS.-M., TroutR.E.L., PozziC., De LucaF., BenvenutiM., ManganiS., LiuB., JacksonR.-W., MoeckG., XerriL., BurnsC.-J., PevearD.-C., and DaigleD.-M.. 2020. VNRX-5133 (Taniborbactam), a broad-spectrum inhibitor of serine- and metallo-β-lactamases, restores activity of cefepime in Enterobacterales and Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 64:e01963-19.
60.
BaiC.-G., XuY.-T., LiN.-N., WangJ.-H., YangC., ChenY., and ZhouH.-G.. 2015. Cysteine and its derivatives as New Delhi metallo-beta-lactamase-1 inhibitors. Curr. Enzyme Inhib. 11:46–57.
61.
Rao, Z., X. Feng, W. Yang, C. Yue, D. Zhang, W. Qiang, and B. Cuikai. 2014. d-Cysteinyl-l-homocysteine propyl benzene ammonia acid dipeptide derivate preparation in New Delhi metal beta-lactamase in 1 inhibitor of use. CN Patent No. 104138594.
62.
Tehrani, K.H.M.E., and MartinN.I.. 2017. Thiol-containing metallo-β-lactamase inhibitors resensitize resistant Gram-negative bacteria to Meropenem. ACS Infect. Dis. 3:711–717.
63.
KhanA.U., A. Ali, Danishuddin, G. Srivastava, and A. Sharma. Potential inhibitors designed against NDM-1 type metallo-β-lactamases: an attempt to enhance efficacies of antibiotics against multi-drug-resistant bacteria. Sci. Rep. 7:1–14.
64.
YangS.-K., KangJ.S., OelschlaegerP., and YangK.-W.. 2015. Azolylthioacetamide: a highly promising scaffold for the development of metallo-β-lactamase inhibitors. ACS Med. Chem. Lett. 6:455–460.
65.
ZhaiL., ZhangY.-L., KangJ.S., OelschlaegerP., XiaoL., NieS.-S., and YangK.-W.. 2016. Triazolylthioacetamide: a valid scaffold for the development of New Delhi metallo-β-lactmase-1 (NDM-1) inhibitors. ACS Med. Chem. Lett. 7:413–417.
66.
XiangY., ChangY.-N., GeY., KangJ.S., ZhangY.-L., LiuX.-L., OelschlaegerP., and YangK.-W.. 2017. Azolylthioacetamides as a potent scaffold for the development of metallo-β-lactamase inhibitors. Bioorg. Med. Chem. Lett. 27:5225–5229.
67.
LiN., LouZ., RaoZ., XiaQ., YangC., ChenY., GuoY., BaiC., and XuY.. 2013. L-Cysteine ester compound in inhibiting NDM-1. CN 103127048.
68.
LiN., XuY., XiaQ., BaiC., WangT., WangL., HeD., XieN., LiL., and WangJ.. 2014. Simplified captopril analogues as NDM-1 inhibitors. Bioorg. Med. Chem. Lett. 24:386–389.
69.
Dai, H., H. Guo, Z. Li, F. Song, H. Tan, J. Wang, W. Wang, and L. Zhang. 2012. Isatin derivative and application thereof for preparing anti-super drug resistant bacteria medicine. CN Patent No. 102464603.
70.
Sacchettini, J.C., J.A. Mire, C.C. Thurman, N.W. Zhou, A. Joachimiak, G. Babnigg, and K. Youngchang. 2015. Novel inhibitors of the New Delhi metallo beta lactamase (NDM-1). WO Patent No. 2015157618.
71.
SkagsethS., AkhterS., PaulsenM.H., MuhammadZ., LauksundS., Ø. Samuelsen, LeirosH.-K.S., and BayerA.. 2017. Metallo-β-lactamase inhibitors by bioisosteric replacement: preparation, activity and binding. Eur. J. Med. Chem. 135:159–173.
72.
Cain, R., J. Brem, D. Zollman, M.A. McDonough, R.M. Johnson, J. Spencer, A. Makena, M.I. Abboud, S. Cahill, and S.Y. Lee. 2018. In silico fragment-based design identifies subfamily B1 metallo-β-lactamase inhibitors. J. Med. Chem. 61:1255–1260.
73.
Cariou, K., R.H. Dodd, E. Romero, M. Benchekroun, B. Iorga, T. Naas, and S. Oueslati. 2018. 2- or 3-Imidazolines as carbapenemases inhibitors. WO Patent No. 2018162670.
74.
HeathT., StewartA., ThomasP., FastW., and BeckerD.. 2016. Design, synthesis, and NDM-1 inhibitory potency of indoline sulfonamides. Abstracts of Papers of the American Chemical Society. American Chemical Society, Washington, DC.
75.
ChenA.Y., ThomasP.W., StewartA.C., BergstromA., ChengZ., MillerC., BethelC.R., MarshallS.H., CredilleC.V., and RileyC.L.. 2017. Dipicolinic acid derivatives as inhibitors of New Delhi metallo-β-lactamase-1. J. Med. Chem. 60:7267–7283.
76.
ZhangE., WangM.-M., HuangS.-C., XuS.-M., CuiD.-Y., BoY.-L., BaiP.-Y., HuaY.-G., XiaoC.-L., and QinS.. 2018. NOTA analogue: a first dithiocarbamate inhibitor of metallo-β-lactamases. Bioorg. Med. Chem. Lett. 28:214–221.
77.
EverettM., SprynskiN., CoelhoA., CastandetJ., BayetM., BougnonJ., LozanoC., DaviesD.T., LeirisS., and ZalacainM.. 2018. Discovery of a novel metallo-ß-lactamase inhibitor, which can potentiate meropenem activity against carbapenem-resistant Enterobacteriaceae. Antimicrob. Agents Chemother. 62:e00074-18.
78.
JinW.B., XuC., ChengQ., QiX.L., GaoW., ZhengZ., ChanE.W., LeungY.-C., ChanT.H., and WongK.-Y.. 2018. Investigation of synergistic antimicrobial effects of the drug combinations of meropenem and 1, 2-benzisoselenazol-3 (2H)-one derivatives on carbapenem-resistant Enterobacteriaceae producing NDM-1. Eur. J. Med. Chem. 155:285–302.
LiuS., ZhouY., NiuX., WangT., LiJ., LiuZ., WangJ., TangS., WangY., and DengX.. 2018. Magnolol restores the activity of meropenem against NDM-1-producing Escherichia coli by inhibiting the activity of metallo-beta-lactamase. Cell Death Discov. 4:28.
81.
KumarR., ChandarB., and ParaniM.. 2018. Use of succinic & oxalic acid in reducing the dosage of colistin against New Delhi metallo-β-lactamase-1 bacteria. Indian J. Med. Res. 147:97.
82.
HaldarJ., and YarlagaddaV.. 2016. Glycopeptides conjugates and uses thereof. Patient No. WO2016125193A1.
KhanS., AliA., and KhanA.U.. 2018. Structural and functional insight of New Delhi Metallo β-lactamase-1 variants. Future Med. Chem. 10:221–229.
85.
Wright, G.D. 2016. Antibiotic adjuvants: rescuing antibiotics from resistance: (Trends in Microbiology 24, 862–871; October 17, 2016). Trends Microbiol. 24:928.
86.
LiuZ., LinY., LuQ., LiF., YuJ., WangZ., HeY., and SongC.. 2017. In vitro and in vivo activity of EDTA and antibacterial agents against the biofilm of mucoid Pseudomonas aeruginosa. Infection, 45:23–31.
87.
SantosA.L., SodreC.L, ValleR.S., SilvaB.A., Abi-ChacraE.A., SilvaL.V., Souza-GoncalvesA.L., SangenitoL.S., GoncalvesD.S., SouzaL.O., PalmeiraV.F., d'Avila-LevyC.M., KneippL.F., KellettA., McCannM., and BranquinhaM.H.. 2012. Antimicrobial action of chelating agents: repercussions on the microorganism development, virulence and pathogenesis. Curr. Med. Chem. 19:2715–2737.
88.
SchnaarsC., Kildahl-AndersenG., PrandinaA., PopalR., RadixS., Le BorgneM., GjøenT., AndresenA.M.S., HeikalA., and O.A. Økstad. 2018. Synthesis and preclinical evaluation of TPA-based zinc chelators as metallo-β-lactamase inhibitors. ACS Infect. Dis. 4:1407–1422.
89.
WangQ., Y. He, R. Lu, W.-M. Wang, K.-W. Yang, H.-M. Fan, Y. Jin, and G.-M. Blackburn. Thermokinetic profile of NDM-1 and its inhibition by small carboxylic acids. Biosci. Rep. 38:1–11.
90.
MaB., C. Fang, L. Lu, M. Wang, X. Xue, Y. Zhou, M. Li, Y. Hu, X. Luo, and Z. Hou. The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1metallo-β-lactamase. Nat. Commun. 10:1–11.
91.
GaoX., ZhaoJ., HanG., ZhangY., DongX., CaoL., WangQ., MoultonH.M., and YinH.. 2014. Effective dystrophin restoration by a novel muscle-homing peptide–morpholino conjugate in dystrophin-deficient mdx mice. Mol. Ther. 22:1333–1341.
92.
Wilkowski, P., M. Ciszek, K. Dobrzaniecka, J. Sańko-Resmer, A. Łabuś, K. Grygiel, T. Grochowiecki, G. Młynarczyk, and L. Pączek. 2016. Successful treatment of urinary tract infection in kidney transplant recipients caused by multiresistant Klebsiella pneumoniae producing New Delhi Metallo-beta-lactamase (NDM-1) with strains genotyping. Transplant. Proc. 48:1576–1579.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
