Extended-spectrum β-lactamases and the permeability barrier

The outer membrane of Gram-negative bacteria represents a barrier for penetration of hydrophilic compounds. Loss of porins (water-filled protein channels) contributes to antimicrobial resistance, particularly when additional mechanisms of resistance are expressed. Many studies on the structure and regulation of porins in Escherichia coli K-12 are available, but there is little information concerning clinical isolates of this species. In Klebsiella pneumoniae, two major porins, OmpK35 and OmpK36, are produced, but many extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolates do not express OmpK35. Loss of both OmpK35 and OmpK36 in ESBL-producing K. pneumoniae causes resistance to cefoxitin, increased resistance to expanded-spectrum cephalosporins, and decreased susceptibility to carbapenems, particularly ertapenem. Porin loss also decreases the susceptibility to other non-beta-lactam compounds, such as fluoroquinolones, of ESBL-producing organisms.

[1]  Jordi Vila,et al.  Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii. , 2007, The Journal of antimicrobial chemotherapy.

[2]  T. Gootz,et al.  High-Level Carbapenem Resistance in a Klebsiella pneumoniae Clinical Isolate Is Due to the Combination of blaACT-1 β-Lactamase Production, Porin OmpK35/36 Insertional Inactivation, and Down-Regulation of the Phosphate Transport Porin PhoE , 2006, Antimicrobial Agents and Chemotherapy.

[3]  A. Robicsek,et al.  The worldwide emergence of plasmid-mediated quinolone resistance. , 2006, The Lancet. Infectious diseases.

[4]  A. Oliver,et al.  Characterization of a Large Outbreak by CTX-M-1-Producing Klebsiella pneumoniae and Mechanisms Leading to In Vivo Carbapenem Resistance Development , 2006, Journal of Clinical Microbiology.

[5]  N. Woodford,et al.  In vivo development of ertapenem resistance in a patient with pneumonia caused by Klebsiella pneumoniae with an extended-spectrum beta-lactamase. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  G. Jacoby,et al.  Role of β-Lactamases and Porins in Resistance to Ertapenem and Other β-Lactams in Klebsiella pneumoniae , 2004, Antimicrobial Agents and Chemotherapy.

[7]  J. Pagés,et al.  Omp35, a New Enterobacter aerogenes Porin Involved in Selective Susceptibility to Cephalosporins , 2004, Antimicrobial Agents and Chemotherapy.

[8]  H. Nikaido.  Molecular Basis of Bacterial Outer Membrane Permeability Revisited , 2003, Microbiology and Molecular Biology Reviews.

[9]  L. Martínez-Martínez,et al.  Role of Klebsiella pneumoniae OmpK35 Porin in Antimicrobial Resistance , 2003, Antimicrobial Agents and Chemotherapy.

[10]  L. Martínez-Martínez,et al.  Energy-Dependent Accumulation of Norfloxacin and Porin Expression in Clinical Isolates of Klebsiella pneumoniae and Relationship to Extended-Spectrum β-Lactamase Production , 2002, Antimicrobial Agents and Chemotherapy.

[11]  V. Benedí,et al.  Expression of SHV-2 β-Lactamase and of Reduced Amounts of OmpK36 Porin in Klebsiella pneumoniae Results in Increased Resistance to Cephalosporins and Carbapenems , 2002, Antimicrobial Agents and Chemotherapy.

[12]  G. Schulz.  The structure of bacterial outer membrane proteins. , 2002, Biochimica et biophysica acta.

[13]  M. Jaquinod,et al.  A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a structural modification of the major porin , 2001, Molecular microbiology.

[14]  G. Mora,et al.  A chromosomal region surrounding the ompD porin gene marks a genetic difference between Salmonella typhi and the majority of Salmonella serovars. , 2001, Microbiology.

[15]  L. Martínez-Martínez,et al.  Activity of nine antimicrobial agents against clinical isolates of Klebsiella pneumoniae producing extended-spectrum beta-lactamases and deficient or not in porins. , 2000, The Journal of antimicrobial chemotherapy.

[16]  L. Martínez-Martínez,et al.  Relationship between outer membrane alterations and susceptibility to antimicrobial agents in isogenic strains of Klebsiella pneumoniae. , 2000, The Journal of antimicrobial chemotherapy.

[17]  J. Pagés,et al.  Comparative aspects of the diffusion of norfloxacin, cefepime and spermine through the F porin channel of Enterobacter cloacae. , 2000, The Biochemical journal.

[18]  G. Jacoby,et al.  Roles of β-Lactamases and Porins in Activities of Carbapenems and Cephalosporins against Klebsiella pneumoniae , 1999, Antimicrobial Agents and Chemotherapy.

[19]  L. Martínez-Martínez,et al.  Identification and Characterization of a New Porin Gene of Klebsiella pneumoniae: Its Role in β-Lactam Antibiotic Resistance , 1999, Journal of bacteriology.

[20]  R. Dutzler,et al.  Crystal structure and functional characterization of OmpK36, the osmoporin of Klebsiella pneumoniae. , 1999, Structure.

[21]  L. Martínez-Martínez,et al.  Development of Resistance during Antimicrobial Therapy Caused by Insertion Sequence Interruption of Porin Genes , 1999, Antimicrobial Agents and Chemotherapy.

[22]  L. Martínez-Martínez,et al.  Porin expression in clinical isolates of Klebsiella pneumoniae. , 1999, Microbiology.

[23]  L. Martínez-Martínez,et al.  Outer Membrane Profiles of Clonally Related Klebsiella pneumoniae Isolates from Clinical Samples and Activities of Cephalosporins and Carbapenems , 1998, Antimicrobial Agents and Chemotherapy.

[24]  M. Viñas,et al.  The role of outer membrane in Serratia marcescens intrinsic resistance to antibiotics. , 1997, Microbiologia.

[25]  L. Pratt,et al.  From acids to osmZ: multiple factors influence synthesis of the OmpF and OmpC porins in Escherichia coli , 1996, Molecular microbiology.

[26]  G. Jacoby,et al.  In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum-cephalosporins , 1996, Antimicrobial agents and chemotherapy.

[27]  A. M. George,et al.  Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. , 1995, Microbiology.

[28]  S. Merino,et al.  Isolation of FC3-11, a bacteriophage specific for the Klebsiella pneumoniae porin OmpK36, and its use for the isolation of porin-deficient mutants , 1995 .

[29]  G. Rummel,et al.  A porin from Klebsiella pneumoniae: sequence homology, three-dimensional model, and complement binding , 1995, Infection and immunity.

[30]  J. Lakey,et al.  Chapter 17 The porin superfamily: diversity and common features , 1994 .

[31]  G. Cornaglia,et al.  Diffusion of meropenem and imipenem through the outer membrane of Escherichia coli K-12 and correlation with their antibacterial activities , 1992, Antimicrobial Agents and Chemotherapy.

[32]  J. Tommassen,et al.  Molecular characterization of an Enterobacter cloacae outer membrane protein (OmpX) , 1991, Journal of bacteriology.

[33]  G. Jacoby,et al.  Activities of beta-lactam antibiotics against Escherichia coli strains producing extended-spectrum beta-lactamases , 1990, Antimicrobial Agents and Chemotherapy.

[34]  H. Nikaido,et al.  Outer membrane protein D2 catalyzes facilitated diffusion of carbapenems and penems through the outer membrane of Pseudomonas aeruginosa , 1990, Antimicrobial Agents and Chemotherapy.

[35]  K. Towner,et al.  Enhanced resistance to cefotaxime and imipenem associated with outer membrane protein alterations in Enterobacter aerogenes. , 1990, The Journal of antimicrobial chemotherapy.

[36]  D. Hooper,et al.  Cross-resistance to fluoroquinolones in multiple-antibiotic-resistant (Mar) Escherichia coli selected by tetracycline or chloramphenicol: decreased drug accumulation associated with membrane changes in addition to OmpF reduction , 1989, Antimicrobial Agents and Chemotherapy.

[37]  S. Mitsuhashi,et al.  Effects of beta-lactamases and omp mutation on susceptibility to beta-lactam antibiotics in Escherichia coli , 1989, Antimicrobial Agents and Chemotherapy.

[38]  A. Medeiros,et al.  Loss of OmpC porin in a strain of Salmonella typhimurium causes increased resistance to cephalosporins during therapy. , 1987, The Journal of infectious diseases.

[39]  A. Yamaguchi,et al.  Identification of porins in outer membrane of Proteus, Morganella, and Providencia spp. and their role in outer membrane permeation of beta-lactams , 1987, Antimicrobial Agents and Chemotherapy.

[40]  H. Nikaido,et al.  Porin channels in Escherichia coli: studies with beta-lactams in intact cells , 1983, Journal of bacteriology.

[41]  H. Nikaido.  Proteins forming large channels from bacterial and mitochondrial outer membranes: porins and phage lambda receptor protein. , 1983, Methods in enzymology.