Role of
            <i>Klebsiella pneumoniae</i>
            OmpK35 Porin in Antimicrobial Resistance

Doménech-Sánchez, Antonio; Martı́nez-Martı́nez, Luis; Hernández-Allés, Santiago; Conejo, M. Carmen; Pascual, Álvaro; Tomás, Juan M.; Albertí, Sebastián; Benedí, Vicente J.

doi:10.1128/aac.47.10.3332-3335.2003

Cited by 142 publications

(121 citation statements)

References 18 publications

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“…Similar observations have been previously reported in K. pneumoniae isolates and generated an interesting debate concerning the selectivity of OmpK35 (10,25,27). We show here that in E. aerogenes, the activities of imipenem and cefepime, two zwitterionic molecules, are only weakly affected compared to large negatively charged drugs, and similar observations were reported with OmpK35 and OmpK36 (12,20,25). Interestingly, an S residue is located in the PhoE eyelet and has been reported to be involved in the rate of uptake of large negatively charged cephalosporins (29).…”

Section: Discussionsupporting

confidence: 76%

“…aerogenes ATCC 15038 displays a marked difference in cephalosporin susceptibility when osmolarity conditions are modified. Interestingly, a recent study reported by Doménech-Sanchez et al (12) described the incidence of OmpK35 and OmpK36 expression on the K. pneumoniae susceptibility towards various antibiotics. Similar observations have been previously reported in K. pneumoniae isolates and generated an interesting debate concerning the selectivity of OmpK35 (10,25,27).…”

Section: Discussionmentioning

confidence: 99%

“…1). The sorbitol has been reported to efficiently downregulate OmpK35 porin expression in K. pneumoniae (12). In Fig.…”

Section: ␤-Lactammentioning

confidence: 99%

“…For the determination of MICs, NB broth was prepared according to Difco recommendations using an NB preparation containing Bacto beef extract (3 g/liter) and Bacto Peptone (5 g/liter) (Difco Laboratories, Detroit, Mich.). E. aerogenes cells were grown in NB broth (51 mOsm/kg) or in NB broth containing 20% sorbitol (1.5 Osm/kg) as previously reported (12,13). The MICs were determined with twofold serial dilutions in adequate broth.…”

Section: Methodsmentioning

confidence: 99%

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Omp35, a New Enterobacter aerogenes Porin Involved in Selective Susceptibility to Cephalosporins

Bornet

Saint

Fetnaci

et al. 2004

Antimicrob Agents Chemother

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In Enterobacter aerogenes, ␤-lactam resistance often involves a decrease in outer membrane permeability induced by modifications of porin synthesis. In ATCC 15038 strain, we observed a different pattern of porin production associated with a variable antibiotic susceptibility. We purified Omp35, which is expressed under conditions of low osmolality and analyzed its pore-forming properties in artificial membranes. This porin was found to be an OmpF-like protein with high conductance values. It showed a noticeably higher conductance compared to Omp36 and a specific location of WNYT residues in the L3 loop. The importance of the constriction region in the porin function suggests that this organization is involved in the level of susceptibility to negative large cephalosporins such as ceftriaxone by bacteria producing the Omp35 porin subfamily.The bacterial porins are major outer membrane proteins that form water-filled channels, allowing the diffusion across the outer membrane of small polar molecules, amino acids, and nutrients (14,18,23). General nonspecific porins, such as OmpF and OmpC from Escherichia coli, form homotrimers in the outer membrane. These porin trimers are constituted by large ␤-barrel monomer subunits which are constricted about halfway through the membrane by an internal loop, loop 3 (L3) (18). Resolution of the three-dimensional structure of the E. coli OmpF and Klebsiella pneumoniae OmpK36 has led to identification of the functional domains of the enterobacterial channels (5,8,13,17).Enterobacter aerogenes is one of the most frequently described gram-negative pathogens responsible for nosocomial respiratory tract infections in France and Belgium (2, 6, 10). This bacterial pathogen harbors a variety of antibiotic resistance mechanisms (7,9,19,24,30). Among them, the modification of outer membrane permeability, a porin deficiency associated with the expression of cephalosporinase activity, is frequently detected in clinical resistant isolates (7,19). We recently isolated a strain with an unusual porin phenotype: this EA3 strain synthesized a mutated Omp36 porin containing a G112D substitution in the L3 domain (19). Despite this prominent role of porins in drug susceptibility, only one porin, Omp36, is today functionally characterized in E. aerogenes (19).The aim of this work was to investigate the structural and functional properties of the second major pore-forming protein produced by the E. aerogenes strain. The sequence and the channel properties of the new porin Omp35 were determined and agree with the biological differences concerning the ␤-lactam susceptibility, observed between the bacteria producing either Omp35 or Omp36. MATERIALS AND METHODSBacterial strains, growth conditions, and antibiotic susceptibility tests. The E. aerogenes ATCC 15038 strain was used as the standard strain. E. aerogenes EAEP289 is a Kan s derivative of the previously described clinical strain EA27 (24). Bacteria were routinely grown in Luria-Bertani (LB) medium or nutrient broth (NB). For the determination of MI...

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

“…1). The sorbitol has been reported to efficiently downregulate OmpK35 porin expression in K. pneumoniae (12). In Fig.…”

Section: ␤-Lactammentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Omp35, a New Enterobacter aerogenes Porin Involved in Selective Susceptibility to Cephalosporins

Bornet

Saint

Fetnaci

et al. 2004

Antimicrob Agents Chemother

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“…The level of susceptibility to β-lactams, including cefepime, cefotetan, cefotaxime and cefpirome, in strains expressing OmpK35 is 4-8 times higher than that conferred by OmpK36 (rEF. 23). …”

Section: Alterations In Porin Expressionmentioning

confidence: 99%

The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria

2008

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Antibiotic‐dependent perturbations of extended spectrum beta‐lactamase producing Klebsiella pneumoniae proteome

et al. 2017

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Extended spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) causes life-threatening infections in susceptible and immuno-compromised individuals. Because of the emergence of multidrug resistance and tolerance, it is crucial to better understand the mechanisms by which ESBL-KP can adapt to antibiotic stress. The aim of this study was to provide an overview of the global proteome changes occurring in ESBL-KP in response to sub-lethal concentrations of the antibiotics doxycycline (DC, bacteriostatic) and streptomycin (SM, bactericidal), which both impair ribosomal synthesis of bacterial proteins. These results represent the greatest experimental coverage of the ESBL-KP proteome yet described. The 1538 proteins, representing 30% of the 5126 predicted KP gene products were identified from the combined experimental groups. Antibiotic stress resulted in significantly elevated levels of 42 proteins for DC and 55 for SM treatments, whereas 53 proteins were reduced for DC- and six for SM-treated bacteria. Specifically, the ESBL-KP response to DC was accompanied by the reduced levels of the porins LamB, CirA, FepA, and OmpC. In contrast to DC, the stress response to SM demonstrated a dramatic increase in the peroxidase detoxification pathway proteins PutA, KatG, KatE, and Dps, which prevent harmful hydroxyl radical formation. The results from this proteomic study are important for understanding adaptive responses to antibiotics, and may provide novel targets for the development of new therapeutic strategies.

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Role of Klebsiella pneumoniae OmpK35 Porin in Antimicrobial Resistance

Cited by 142 publications

References 18 publications

Omp35, a New Enterobacter aerogenes Porin Involved in Selective Susceptibility to Cephalosporins

Omp35, a New Enterobacter aerogenes Porin Involved in Selective Susceptibility to Cephalosporins

The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria

Antibiotic‐dependent perturbations of extended spectrum beta‐lactamase producing Klebsiella pneumoniae proteome

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