DHA-1 plasmid-mediated AmpC β-lactamase expression and regulation of Klebsiella pnuemoniae isolates

Luan,Ying; Li,Gui-Ling; Duo,Li-Bo; Wang,Wei-Ping; Wang,Cheng-Ying; Zhang,He-Guang; He,Fei; He,Xin; Chen,Shu-Juan; Luo,Dan-Ting

doi:10.3892/mmr.2014.3054

DHA-1 plasmid-mediated AmpC β-lactamase expression and regulation of Klebsiella pnuemoniae isolates

Authors:
- Ying Luan
- Gui-Ling Li
- Li-Bo Duo
- Wei-Ping Wang
- Cheng-Ying Wang
- He-Guang Zhang
- Fei He
- Xin He
- Shu-Juan Chen
- Dan-Ting Luo
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Affiliations: Department of Medicine Laboratory, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Medicine Laboratory, Department of Urology Surgery, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163001, P.R. China, Department of Medicine Laboratory, Hospital of Harbin Institute of Technology, Harbin, Heilongjiang 150001, P.R. China, Department of Medicine Laboratory, The Fourth People's Hospital of Shenyang, Shenyang, Liaoning 110031, P.R. China
Published online on: December 5, 2014 https://doi.org/10.3892/mmr.2014.3054
Pages: 3069-3077

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Abstract

The present study aimed to investigate the regulatory mechanism of the AmpC enzyme by analyzing the construction and function of AmpCR, AmpE and AmpG genes in the Dhahran (DHA)‑1 plasmid of Klebsiella pneumoniae (K. pneumoniae). The production of AmpC and extended‑spectrum β‑lactamase (ESBL) were determined following the cefoxitin (FOX) inducing test for AmpC, preliminary screening and confirmation tests for ESBL in 10 DHA‑1 plasmid AmpC enzymes of K. pneumoniae strains. AmpCR, AmpD, AmpE and AmpG sequences were analyzed by polymerase chain reaction. The pACYC184‑X plasmid analysis system was established and examined by regulating the pAmpC enzyme expression. The electrophoretic bands of AmpCR, AmpD, AmpE and AmpG were expressed. Numerous mutations in AmpC + AmpR (AmpCR) and in the intergenic region cistron of AmpC‑AmpR, AmpD, AmpE and AmpG were observed. The homology of AmpC and AmpR, in relation to the Morganella morganii strain, was 99%, which was determined by comparing the gene sequences of Kp1 with those of Kp17 AmpCR. The specific combination of AmpR and labeled probe demonstrated a band retarded phenomenon and established a spatial model of AmpR. All the enzyme production strains demonstrated Val93→Ala in AmpG; six transmembrane domains were found in AmpE in all strains, with the exception of Kp1 and Kp4, which had only three transmembrane segments that were caused by mutation. The DHA‑1 plasmid AmpC enzymes encoded by plasmid are similar to the inducible chromosomal AmpC enzymes, which are also regulated by AmpD, AmpE, AmpR and AmpG.

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1	Ehrmann E, Handal T, Tamanai-Shacoori Z, Bonnaure-Mallet M and Fosse T: High prevalence of β-lactam and macrolide resistance genes in human oral Capnocytophaga species. J Antimicrob Chemother. 69:381–384. 2014. View Article : Google Scholar
2	Raji MA, Jamal W, Ojemhen O and Rotimi VO: Point-surveillance of antibiotic resistance in Enterobacteriaceae isolates from patients in a Lagos Teaching Hospital, Nigeria. J Infect Public Health. 6:431–437. 2013. View Article : Google Scholar : PubMed/NCBI
3	Bush K, Jacoby GA and Medeiros AA: A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. 39:1211–1233. 1995. View Article : Google Scholar : PubMed/NCBI
4	Ambler RP, Coulson AF, Frère JM, et al: A standard numbering scheme for the class A beta-lactamases. Biochem J. 15:269–270. 1991.
5	Philippon A, Arlet G and Jacoby GA: Plasmid-determined AmpC-type beta-lactamases. Antimicrob Agents Chemother. 46:1–11. 2002. View Article : Google Scholar
6	Garcia DL and Dillard JP: Mutations in ampG or ampD affect peptidoglycan fragment release from Neisseria gonorrhoeae. J Bacteriol. 190:3799–3807. 2008. View Article : Google Scholar : PubMed/NCBI
7	Jacobs C: Pharmacia Biotech & Science prize. 1997 grand prize winner Life in the balance: cell walls and antibiotic resistance. Science. 278:1731–1732. 1997. View Article : Google Scholar : PubMed/NCBI
8	Wiedemann B, Pfeifle D, Wiegand I and Janas E: beta-Lactamase induction and cell wall recycling in gram-negative bacteria. Drug Resist Updat. 1:223–226. 1998. View Article : Google Scholar
9	Jacobs C, Joris B, Jamin M, et al: AmpD, essential for both β-lactamase regulation and cell wall recycling, is a novel cytosolic N-acetylmuramyl-L-alanine amidase. Mol Microbiol. 15:553–559. 1995. View Article : Google Scholar : PubMed/NCBI
10	Yu WL, Ko WC, Cheng KC, et al: Institutional spread of clonally related Serratia marcescens isolates with a novel AmpC cephalosporinase (S4): a 4-year experience in Taiwan. Diagn Microbiol Infect Dis. 61:460–467. 2008. View Article : Google Scholar : PubMed/NCBI
11	Roh IK, Kim IJ, Chung JH and Byun SM: Affinity purification and binding characteristics of Citrobacter freundii AmpR, the transcriptional regulator of the ampC beta-lactamase gene. Biotechnol Appl Biochem. 23:149–154. 1996.PubMed/NCBI
12	Jacobs C, Huang LJ, Bartowsky E, Normark S and Park JT: Bacterial cell wall recycling provides cytosolic muropeptides as effectors for beta-lactamase induction. EMBO J. 13:4684–4694. 1994.PubMed/NCBI
13	Li JB, Cheng J, Yin J, et al: Progress on AmpC beta-lactamases. Curr Bioinform. 4:218–225. 2009. View Article : Google Scholar
14	Jacoby GA: AmpC beta-lactamases. Clin Microbiol Rev. 22:161–182. 2009. View Article : Google Scholar : PubMed/NCBI
15	Schmidtke AJ and Hanson ND: Model system to evaluate the effect of ampD mutations on AmpC-mediated beta-lactam resistance. Antimicrob Agents Chemother. 50:2030–2037. 2006. View Article : Google Scholar : PubMed/NCBI
16	Khanal S, Joshi DR, Bhatta DR, Devkota U and Pokhrel BM: β-lactamase-producing multidrug-resistant bacterial pathogens from tracheal aspirates of intensive care unit patients at National Institute of Neurological and Allied Sciences, Nepal. ISRN Microbiol. 2013:8475692013. View Article : Google Scholar
17	Pai H, Kang CI, Byeon JH, et al: Epidemiology and cahnical features of blood stream infections caused by AmpC-type-beta-lactamase-producing Klebsiella pneumoniae. Antimiciob Agents Chemother. 48:3720–3728. 2004. View Article : Google Scholar
18	Moland ES: Newer β-Lactamases: clinical and laboratory implications, Part II. Clinical Microbiology Newsletter. 30:79–85. 2008. View Article : Google Scholar
19	Moland ES: Newer β-Lactamases: clinical and laboratory implications, Part I. Clinical Microbiology Newsletter. 30:71–77. 2008. View Article : Google Scholar
20	Gniadkowski M: Evolution and epidemiology of extended-spectrum beta-lactamases (ESBLs) and ESBL-producing microorganisms. Clin Microbiol Infect. 7:597–608. 2001. View Article : Google Scholar : PubMed/NCBI
21	Lodge J, Busby S and Piddock L: Investigation of the Pseudomonas aeruginosa ampR gene and its role at the chromosomal ampC beta-lactamase promoter. FEMS Microbiol Lett. 111:315–320. 1993.PubMed/NCBI
22	Campbell JI, Ciofu O and Høiby N: Pseudomonas aeruginosa isolates from patients with cystic fibrosis have different beta-lactamase expression phenotypes but are homogeneous in the ampC-ampR genetic region. Antimicrob Agents Chemother. 41:1380–1384. 1997.PubMed/NCBI
23	Poirel L, Guibert M, Girlich D, Naas T and Nordmann P: Cloning, sequence analyses, expression, and distribution of ampC-ampR from Morganella morganii clinical isolates. Antimicrob Agents Chemother. 43:769–776. 1999.PubMed/NCBI
24	Balasubramanian D, Schneper L, Merighi M, et al: The regulatory repertoire of Pseudomonas aeruginosa AmpC ß-lactamase regulator AmpR includes virulence genes. PLoS One. 7:e340672012. View Article : Google Scholar
25	Balcewich MD, Reeve TM, Orlikow EA, et al: Crystal structure of the AmpR effector binding domain provides insight into the molecular regulation of inducible ampc beta-lactamase. J Mol Biol. 400:998–1010. 2010. View Article : Google Scholar : PubMed/NCBI
26	Nakano R, Okamoto R, Nakano Y, et al: CFE-1, a novel plasmid-encoded AmpC beta-lactamase with an ampR gene originating from Citrobacter freundii. Antimicrob Agents Chemother. 48:1151–1158. 2004. View Article : Google Scholar : PubMed/NCBI
27	Lee Y, Choi H, Yum JH, et al: Molecular mechanisms of carbapenem resistance in Enterobacter cloacae clinical isolates from Korea and clinical outcome. Ann Clin Lab Sci. 42:281–286. 2012.PubMed/NCBI
28	Fortineau N, Poirel L and Nordmann P: Plasmid-mediated and inducible cephalosporinase DHA-2 from Klebsiella pneumoniae. J Antimicrob Chemother. 47:207–210. 2001. View Article : Google Scholar : PubMed/NCBI
29	Decré D, Verdet C, Raskine L, et al: Characterization of CMY-type beta-lactamases in clinical strains of Proteus mirabilis and Klebsiella pneumoniae isolated in four hospitals in the Paris area. J Antimicrob Chemother. 50:681–688. 2002. View Article : Google Scholar : PubMed/NCBI
30	Carrasco-López C, Rojas-Altuve A, Zhang W, et al: Crystal structures of bacterial peptidoglycan amidase AmpD and an unprecedented activation mechanism. J Biol Chem. 286:31714–31722. 2011. View Article : Google Scholar : PubMed/NCBI
31	Lee M, Zhang W, Hesek D, et al: Bacterial AmpD at the crossroads of peptidoglycan recycling and manifestation of antibiotic resistance. J Am Chem Soc. 131:8742–8743. 2009. View Article : Google Scholar : PubMed/NCBI
32	Bauvois B: Transmembrane proteases in focus: diversity and redundancy? J Leukoc Biol. 70:11–17. 2001.PubMed/NCBI
33	Lindquist S, Galleni M, Lindberg F and Normark S: Signalling proteins in enterobacterial AmpC β-lactamase regulation. Mol Microbiol. 3:1091–1102. 1989. View Article : Google Scholar : PubMed/NCBI
34	Honoré N, Nicolas MH and Cole ST: Regulation of enterobacterial cephalosporinase production: the role of a membrane-bound sensory transducer. Mol Microbiol. 3:1121–1130. 1989. View Article : Google Scholar : PubMed/NCBI
35	Zhang Y, Bao Q, Gagnon LA, et al: ampG gene of Pseudomonas aeruginosa and its role in β-Lactamase expression. Antimicrob Agents Chemother. 54:4772–4779. 2010. View Article : Google Scholar : PubMed/NCBI
36	Chahboune A, Decaffmeyer M, Brasseur R and Joris B: Membrane topology of the Escherichia coli AmpG permease required for recycling of cell wall anhydromuropeptides and AmpC beta-lactamase induction. Antimicrob Agents Chemother. 49:1145–1149. 2005. View Article : Google Scholar : PubMed/NCBI
37	Schmidt H, Korfmann G, Barth H and Martin HH: The signal transducer encoded by ampG is essential for induction of chromosomal AmpC β-lactamase in Escherichia coli by beta-lactam antibiotics and ‘unspecific’ inducers. Microbiology. 141:1085–1092. 1995. View Article : Google Scholar
38	Korfmann G and Sanders CC: ampG is essential for high level expression of AmpC β-lactamase in Enterobacter cloacae. Antimicrob Agents Chemother. 33:1946–1951. 1989. View Article : Google Scholar : PubMed/NCBI