Role of permeability barriers in resistance to β-lactam antibiotics

Nikaido, Hiroshi

doi:10.1016/0163-7258(85)90069-5

Cited by 127 publications

(102 citation statements)

References 110 publications

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“…This hypothesis is consistent with the fact that the hydrophilic /?-lactams are known to cross the outer membrane of Gram-negative bacteria mainly through the non-specific porin channels (Hancock, 1985 ;Nikaido, 1985), but also through the lipid bilayer according to their degree of hydrophobicity (Nikaido, 1985(Nikaido, , 1990). …”

Section: Discussionsupporting

confidence: 64%

“…In contrast, E. coli is thought to have as many as 60000 functional channels per cell. The low permeability of the P. aerzlginosa outer membrane was also confirmed by Yoshimura & Nikaido (1985) with other permeation measurements. N. O R A N G E saturated fatty acids increases when the growth temperature decreases to maintain membrane fluidity (Bha koo & Herbert, 1780;Russell, 1770;Russell & Fukunaga, 1770).…”

Section: Introductionsupporting

confidence: 65%

“…Numerous studies have shown that in all Gramnegative bacteria, transmembraneous protein channels, called porins, allow the penetration of hydrophilic solutes by passive diffusion, the rate of which depends, at least in the case of the major non-specific porins on the size and other physicochemical properties of the solute (Hancock, 1987;Nikaido, 1985). In contrast, hydrophobic molecules penetrate by diffusion through the lipid bilayer, although the presence of lipopolysaccharides (LPS) as a major constituent of the outer layer, strongly decreases this type of permeability (Hancock, 1985 ;Nikaido, 1985Nikaido, , 1990). …”

Section: Introductionmentioning

confidence: 99%

“…O R A N G E mezlocillin have a much lower permeability rate than that expected from their hydrophobicity. These molecules may, at least partly, also follow the penetration route of hydrophobic molecules through the lipid bilayer (Nikaido, 1985(Nikaido, ,1990. To increase the permeability to the antibiotic of the outer membrane lipid bilayer, the lipopolysaccharide (LPS) must be altered by a permeabilizer such as Na-EDTA Vaara, 1990).…”

mentioning

confidence: 99%

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Growth temperature regulates the induction of -lactamase in Pseudomonas fluorescens through modulation of the outer membrane permeation of a -lactam-inducing antibiotic

Orange¹

1994

Microbiology

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The psychrotrophic bacterium, Pseudomonas fluorescens strain MFO, is more sensitive t o the p-lactam mezlocillin at a low growth temperature (i.e. 8 "C) than at a higher growth temperature (28 "C). An early effect of this antibiotic at all temperatures is bacterial filamentation, but this occurs later at 8 "C than at 28 "C, which suggests a lower permeability of the cell envelopes to mezlocillin at low growth temperature. /3-Lactamase production is later induced by mezlocillin, but the level of this induction also depends on the growth temperature, the overall induction being much less efficient at 8 "C. It is hypothesized that the periplasmic concentration of the drug might be too low at 8 "C to allow efficient 8-lactamase induction; this hypothesis was confirmed by the demonstration that p-lactamase production is drastically enhanced in cells cultivated at 8 "C permeabilized for 10 min by Na-EDTA. In addition, induction kinetic curves display a marked dependence upon growth temperature. A rapid saturation was evident when mezlocillin concentrations were increased at 8 "C; this was not seen at 28 "C at up to 1000 pg mezlocillin ml-l. The results are discussed in terms of two different routes of drug permeation, depending on the growth temperature.Keywords : Pseudomonas fluorescens, /3-lactamase induction, outer membrane permeability, growth temperature regulation, psychrophile INTRODUCTIONPsetrdomonas flzlorescens, a Gram-negative bacterium, is surrounded by an outer membrane that acts as the first permeability barrier to the entrance of molecules into the cell. Numerous studies have shown that in all Gramnegative bacteria, transmembraneous protein channels, called porins, allow the penetration of hydrophilic solutes by passive diffusion, the rate of which depends, at least in the case of the major non-specific porins on the size and other physicochemical properties of the solute (Hancock, 1987;Nikaido, 1985). In contrast, hydrophobic molecules penetrate by diffusion through the lipid bilayer, although the presence of lipopolysaccharides (LPS) as a major constituent of the outer layer, strongly decreases this type of permeability (Hancock, 1985 ;Nikaido, 1985Nikaido, , 1990).The permeability of Psezldomonas aerzlginosa, a species belonging like P. flzlorescens to the fluorescent pseudomonads, has been much studied (Hancock, 1987(Hancock, , 1991 Hancock e t al., 1990). This species is highly impermeable (thus resistant) to most P-lactams, so the P-lactams that are able to penetrate have often been used to analyse the routes of molecule permeation in P. aerzlginosa. This occurs mainly through non-specific porins, as shown with porin-deficient mutants (Nicas & Hancock, 1983). The diffusion rate depends on hydrophobicity of the molecules (Nikaido e t al., 1979; Bavoil e t al., 1977). In addition, Hancock (1985) has shown by measurement of nitrocefin permeation that the permeability of the P. aerzrgilzosa outer membrane is 12-fold lower than that of the Escbericbia coli outer membrane and has demonstrated that onl...

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Section: Discussionsupporting

confidence: 64%

Section: Introductionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Growth temperature regulates the induction of -lactamase in Pseudomonas fluorescens through modulation of the outer membrane permeation of a -lactam-inducing antibiotic

Orange¹

1994

Microbiology

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“…Indeed, the broad-spectrum resistance of this organism is largely due to a low outer-membrane permeability (32,33) and to multidrug resistance (MDR) efflux systems (25,26,32,35). Moreover, P. aeruginosa possesses an inducible chromosomally encoded AmpC cephalosporinase belonging to Ambler class C (6).…”

mentioning

confidence: 99%

Nosocomial Outbreak Due to a Multiresistant Strain of Pseudomonas aeruginosa P12: Efficacy of Cefepime-Amikacin Therapy and Analysis of β-Lactam Resistance

et al. 2001

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Over a 3-year period, 67 patients of the Hospital of Pau (Pau, France), including 64 patients hospitalized in the adult intensive care unit (ICU), were colonized and/or infected by strains of Pseudomonas aeruginosa P12, resistant to all potentially active antibiotics except colistin. Most patients were mechanically ventilated and presented respiratory tract infections. Since cefepime and amikacin were the least inactive antibiotics by MIC determination, all ICU patients were treated with this combination, and most of them benefited. Cefepimeamikacin was found highly synergistic in vitro. Ribotyping and arbitrary primer-PCR analysis confirmed the presence of a single clonal isolate. Isoelectrofocusing revealed that the epidemic strain produced large amounts of the chromosomal cephalosporinase and an additional enzyme with a pI of 5.7, corresponding to PSE-1, as demonstrated by PCR and sequencing. Outer membrane protein profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the absence of a ca. 46-kDa protein, likely to be OprD, and increased production of two ca. 49-and 50-kDa proteins, consistent with the outer membrane components of the efflux systems, MexAB-OprM and MexEF-OprN. Thus, we report here a nosocomial outbreak due to multiresistant P. aeruginosa P12 exhibiting at least four mechanisms of ␤-lactam resistance, i.e., production of the penicillinase PSE-1, overproduction of the chromosomal cephalosporinase, loss of OprD, and overexpression of efflux systems, associated with a better activity of cefepime than ceftazidime.Pseudomonas aeruginosa, like many other nonfermenting gram-negative rods, is a saprophytic organism widespread in nature, particularly in moist environments (water, soil, plants, and sewage), and endowed with only weak pathogenic potential. However, because of its ability to survive on inert materials and its resistance to most antiseptics and antibiotics, P. aeruginosa has become an important and frequent nosocomial pathogen. Indeed, in hospitals, sinks, respiratory therapy equipment, and antiseptic or detergent solutions can act as reservoirs of P. aeruginosa. This organism is responsible for a wide range of hospital-acquired infections such as pneumonia, urinary tract infections, or bacteremia. Patients with impaired specific or nonspecific defense systems particularly tend to suffer from severe and even fatal infections caused by P. aeruginosa (9,11,23,24). Cross-transmission from patient to patient may occur via the hands of the health care staff or through contaminated materials or reagents (2, 18, 21, 24). Thus, a number of outbreaks of nosocomial infections due to P. aeruginosa have been reported, especially in intensive care units (ICUs) (2, 11, 18, 24), burn wound units (21), and cancer centers (23).One feature of P. aeruginosa is its high level of intrinsic resistance to a number of structurally unrelated antimicrobial agents. Indeed, the broad-spectrum resistance of this organism is largely due to a low outer-membrane permeability (32,33) and to multidrug...

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Antibacterial Therapy

Gould¹

2010

Topley &Amp; Wilson's Microbiology and Microbial Infections

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Role of permeability barriers in resistance to β-lactam antibiotics

Cited by 127 publications

References 110 publications

Growth temperature regulates the induction of -lactamase in Pseudomonas fluorescens through modulation of the outer membrane permeation of a -lactam-inducing antibiotic

Growth temperature regulates the induction of -lactamase in Pseudomonas fluorescens through modulation of the outer membrane permeation of a -lactam-inducing antibiotic

Nosocomial Outbreak Due to a Multiresistant Strain of Pseudomonas aeruginosa P12: Efficacy of Cefepime-Amikacin Therapy and Analysis of β-Lactam Resistance

Antibacterial Therapy

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