Correlation of porin genes loss with resistance to carbapenems in Klebsiella pneumoniae

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LI Kun(Department of Clinical Laboratory, the First People's Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China)
SHI Wei-feng(Department of Clinical Laboratory, the First People's Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China)
JI Yun(Department of Clinical Laboratory, the First People's Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China)
WANG Yu-yue(Department of Clinical Laboratory, the First People's Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China)
MI Zu-huang()
Journal Title:
Volume 04, Issue 03, 2011
Key Word:
Klebsiella pneumoniae;Carbapenem;β-lactamase;Porin

Abstract: Objective To investigate the molecular mechanism of Klebsiella pneumoniae resistant to carbapenem. Methods The minimal inhibitory concentrations ( MICs) of the antimicrobial agents were determined by E-test. The 23 β-lactamase genes and 2 porin genes were amplified by polymerase chain reaction (PCR) , then the products were purified and their sequences were analyzed. Results The MICs of piperacillin, piperacillin/sulbactam, amoxicillin/clavulanic acid, cefoperazone/sulbactam, cefotaxime, cefepime and aztreonam to 5 strains of Klebsiella pneumoniae were all higher than 128 μg/mL, and those of imipenem or meropenem were higher than 32 μg/mL. All isolates carried blaTEM-1 and blaDHA-1 genes. Deletion of ompK35 and ompK36 were observed in Kp01 and Kp03, and the deletion of ompK35 was also observed in Kp02 and Kp05. Base insertion of ompK36 occurred in Kp02, Kp04 and Kp05. Compared with GenBank (GU945384) , ompK35 gene mutations of G→C at base 465 and T → C at base 466 in Kp04 lead to Gln to His substitution at position 155 and Tyr to its substitution at position 156, and it might be a new subtype. Conclusion The production of DHA-1 β-lactamase combined with the loss of OmpK36 or OmpK35 in porin genes may contribute to high-level carbapenem resistance in Klebsiella pneumoniae.

  • [1]Gasink LB,Edelstein PH,Lautenbach E,et al.Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase-producing K.pneumoniae.Infect Control Hosp Epidemiol,2009,30(12):1180-1185.
  • [2]Giamarellou H,Poulakou G.Multidrug-resistant gram-negative infections:what are the treatment options? Drugs,2009,69 (14):1879-1901.
  • [3]Villegas MV,Lolans K,Correa A,et al.First detection of the plasmid-mediated class A carbapenemase KPC-2 in clinical isolates of Klebsiella pneumoniae from South America.Antimicrob Agents Chemother,2006,50(8):2880-2882.
  • [4]Ke W,Bethel CR,Thomson JM,et al.Crystal structure of KPC2:insights into carbapenemase activity in class A beta-laetamases.Biochemistry,2007,46(19):5732-5740.
  • [5]Wei ZQ,Du XX,Yu YS,et al.Plasmid-mediated KPC-2 in a Klebsiella pneumoniae isolate from China.Antimicrob Agents Chemother,2007,51 (2):763-765.
  • [6]Clímaco EC,Minarini LA,da Costa Darini AL.CTX-M-producing Klebsiella a Brazilian hospital:what has changed in 6 years? Diagn Microbiol Infect Dis,2010,68(2):186-189.
  • [7]Sturenburg E,Sobottka I,Mack D,et al.Cloning and sequencing of Enterobacter aerogenes OmpC-type osmoporin linked to carbapenem resistance.Int J Med Microbiol,2002,291 (8):649-654.
  • [8]Achouak W,Pages JM,De Mot R,et al.A major outer membrane protein of Rahnella aquatilis functions as a porin and root adhesin.J Bacteriol,1998,180(4):909-913.
  • [9]Song W,Suh B,Choi JY,et al.In vivo selection of carbapenemresistant Klebsiella pneumoniae by OmpK36 loss during meropenem treatment.Diagn Microbiol Infect Dis,2009,65(4):447-449.
  • [10]Hernández-Allés S,Albertí S,Alvarez D,et al.Porin expression in clinical isolates of Klebsiella pneumoniae.Microbiol,1999,145 (pt3):673-679.
  • [11]Palasubramaniam S,Muniandy S,Navaratnam P,et al.Resistance to extended-spectrum beta-lactams by the emergence of SHV-12 and the loss of OmpK35 in Klebsiella pneumoniae and Escherichia coli in Malaysia.J Microbiol Immunol Infect,2009,42(2):129-133.
  • [12]Yang D,Guo Y,Zhang Z,et al.Combined porin loss and extended spectrum beta-lactamase production is associated with an increasing imipenem minimal inhibitory concentration in clinical Klebsiella pneumoniae strains.Curr Microbiol,2009,58 (4):366-370.
  • [13]Kaczmarek FM,Dib-Hajj F,Shang W,et al.High-level carbapenem resistance in a Klebsiella pneumoniae clinical isolate is due to the combination of bla(ACT-1) beta-lactamase production,porin OmpK35/36 insertional inactivation,and down-regulation of the phosphate transport porin phoe.Antimicrob Agents Chemother,2006,50(10):3396-3406.
  • [14]Pournaras S,Poulou A,Voulgari E,et al.Detection of the new metallo-beta-lactamase VIM-19 along with KPC-2,CMY-2 and CTX-M-15 in Klebsiella pneumoniae.J Antimicrob Chemother,2010,65(8):1604-1607.
  • [15]Leavitt A,Navon-Venezia S,Chmelnitsky I,et al.Emergence of KPC-2 and KPC-3 in carbapenem-resistant Klebsiella pneumoniae strains in an Israeli hospital.Antimicrob Agents and Chemother,2007,51(8):3026-3029.
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