Effects of Carbon Sources on Antibiotic Resistance in
            <i>Pseudomonas aeruginosa</i>

Conrad, Robert; Wulf, R. Gary; Clay, Damonda L.

doi:10.1128/aac.15.1.59

Cited by 27 publications

(21 citation statements)

References 15 publications

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“…Alteration of outer membrane permeability leading to drug resistance has sometimes been associated with modification of phospholipid composition, in particular for antibiotics interacting with components of the outer membrane, such as polymyxin B and aminoglycosides (7,8). No such changes were identified in this study (Fig.…”

Section: Discussioncontrasting

confidence: 39%

“…Bacterial cells were grown in nutrient broth to early stationary phase, harvested by centrifugation, washed twice with saline, suspended in water, and freezedried. The readily extractable lipid fraction was obtained by chloroform-methanol (2:1) extraction by the method of Folch et al (11), as modified by Conrad et al (8). The phosphate content of the readily extractable lipid fraction was determined by the method of Ames and Dubin (1).…”

Section: Methodsmentioning

confidence: 99%

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Characterization of mechanisms of quinolone resistance in Pseudomonas aeruginosa strains isolated in vitro and in vivo during experimental endocarditis

Chamberland

Bayer

Schollaardt

et al. 1989

Antimicrob Agents Chemother

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Mechanisms of resistance to quinolones were characterized in Pseudomonas aeruginosa strains isolated after Tn5 insertional mutagenesis and in resistant strains that emerged during pefloxacin therapy of experimental aortic endocarditis. Quinolone resistance achieved in in vitro-selected mutants Qr_1 and Qr-2 was associated with cross-resistance to several groups of antimicrobial agents, including ,-lactams, tetracycline, and chloramphenicol. A significant reduction of norfloxacin uptake was also observed. After ether permeabilization of the cells, DNA synthesis of these two isolates was as susceptible to norfloxacin as DNA synthesis of the parent strain (PAO1). These results indicate that alteration of outer membrane permeability is the primary determinant of resistance in these isolates. This altered cell permeability was correlated with reduction of outer membrane protein G (25.5 kilodaltons) and loss of a 40-kilodalton outer membrane protein in strain Qr_l. Resistance to quinolones that emerged during experimental endocarditis therapy was associated with both modification of outer membrane permeability (decreased uptake of norfloxacin) and decreased susceptibility of DNA synthesis to norfloxacin. Resistance was limited to quinolones and chloramphenicol. For these strains, norfloxacin inhibitory doses (50%) for DNA synthesis were identical to the drug MICs, suggesting that despite the identification of a permeability change, perhaps due to changes of lipopolysaccharide, the alteration of the quinolone intracellular target(s) susceptibility constitutes the primary determinant of resistance. Also, two distinct levels of norfloxacin resistance of DNA synthesis were found in these isolates, indicating that at least two distinct alterations of the drug target(s) are possible in P. aeruginosa.New fluoroquinolones, such as ciprofloxacin and norfloxacin, have potent antimicrobial activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa (48). Biochemical and genetic evidence has designated the DNA gyrase (subunit A) as the intracellular target of these drugs. Bacterial DNA gyrase is a tetramer of two of each of the subunits, A and B, encoded by the gyrA and gyrB genes, respectively. DNA gyrase catalyzes DNA supercoiling, which serves important functions in DNA replication, recombination, and repair (12). Inhibition of DNA gyrase activities by quinolones leads to inhibition of DNA synthesis, but the mechanisms by which quinolones induce cell death and the exact molecular interactions existing between quinolones, DNA gyrase, and DNA are not clear (24).Mutational resistance to fluoroquinolones in gram-negative bacteria such as Escherichia coli and P. aeruginosa has been associated with modification of the intracellular target of the drug (DNA gyrase) or alteration of outer membrane permeability (21,25,42,48).In E. coli, mutations that affect both gyrase subunits, leading to various levels of resistance to fluoroquinolones and nalidixic acid, have been described (24), while in P. aeruginos...

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Section: Discussioncontrasting

confidence: 39%

Section: Methodsmentioning

confidence: 99%

Characterization of mechanisms of quinolone resistance in Pseudomonas aeruginosa strains isolated in vitro and in vivo during experimental endocarditis

Chamberland

Bayer

Schollaardt

et al. 1989

Antimicrob Agents Chemother

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“…Each nutrient is often consumed through a dedicated utilization pathway that imports the nutrient into the cytoplasm and then shunts the nutrient into cellular metabolism. Utilization pathways in bacteria have been extensively studied for over 60 years to understand the molecular basis of gene regulation (1), although nutrient utilization has received renewed interest because of its impact on how probiotics and pathogens colonize the human gut, how antibiotic resistance genes are spread through horizontal gene transfer, and how these properties can be used in engineering microbial chemical factories (2)(3)(4)(5).…”

mentioning

confidence: 99%

Rethinking the Hierarchy of Sugar Utilization in Bacteria

Beisel

Afroz

2016

J Bacteriol

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“…We planned the present study to create modifications in the cell surface of E. coli by using various growth media to investigate the role of yet uncharacterized components in ceftazidime susceptibility. This work was based on a previous study that showed that bacterial growth in various media results in changes in lipid composition (7) and that studies with bacteria with mutations that affect the structure of the LPS-phospholipid bilayer showed changes in bacterial susceptibility to hydrophobic or membrane-interacting antibiotics (20). The hope was to change E. coli surface properties (hydrophobicity and phospholipid content) to investigate a possible nonspecific lipophilic diffusion pathway for ceftazidime.…”

Section: Discussionmentioning

confidence: 99%

Influence of growth media on Escherichia coli cell composition and ceftazidime susceptibility

Malouin

Chamberland

Brochu

et al. 1991

Antimicrob Agents Chemother

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Cell composition and surface properties of Escherichia coli were modified by using various growth media to investigate the role of yet uncharacterized components in ceftazidime susceptibility. An eightfold dilution of Luria broth was used as the basic growth medium and was supplemented with up to 4% phosphate, 5% glucose, or 12% L-glutamate. Decreases in cephaloridine and ceftazidime susceptibility, of two-and eightfold, respectively, were observed only in the glucose-enriched medium. The outer membrane permeability to ceftazidime and cephaloridine was evaluated by crypticity indices. Indices were unchanged under all growth conditions. Fluorometry of whole cells with 1-N-phenylnaphthylamine showed that glucose does not affect the interaction of this hydrophobic probe with the membranes but showed that elevated concentrations of phosphate or glutamate cause a marked increase in cell hydrophobicity, which, in turn, correlates with an increase in the susceptibility of E. coli to nalidixic acid. Growth in phosphate-or glutamate-enriched media caused an augmentation in major phospholipid species and may explain the increased hydrophobicity and susceptibility of E. coli to nalidixic acid. These data showed that E. coli susceptibility to ceftazidime is not influenced by cell surface hydrophobicity and suggested that the contribution of a nonspecific lipophilic diffusion route for entry of ceftazidime into cells is not likely to occur or is distinct from that of more hydrophobic molecules such as nalidixic acid. Finally, the penicillin-binding proteins of the E. coli cells were also investigated. Penicillin-binding protein 8 was only markedly labeled with 125I-penicillin V in inner membranes extracted from cells grown with glucose. Results of this study suggest that the unexpected change in penicillin-binding protein 8 observed in the presence of glucose may be responsible for the increase in MICs of cephaloridine and ceftazidime.In general, the susceptibility of gram-negative bacteria to ,B-lactam antibiotics results from the relative effect of the outer membrane permeability and the periplasmic ,-lactamase on the P-lactam periplasmic concentration. In turn, the periplasmic antibiotic concentration needed to affect the antibiotic inner membrane cell targets (the penicillin-binding proteins [PBPs]) depends on the affinities of these PBPs for the P-lactam (33).Ceftazidime is a very potent broad-spectrum cephalosporin against members of the family Enterobacteriaceae and Pseudomonas spp. (9, 25), although it has been reported to have an unusually slow diffusion rate through the outer membrane of gram-negative bacteria (34). Recently, Nikaido and Normark (21) constructed a mathematical model to predict 3-lactam MICs from the antibiotic penetration rate through the outer membrane and the P-lactamase hydrolysis rate in the periplasm. In the case of ceftazidime,'the observed MIC was significantly different from the predicted value, and it was suggested that ceftazidime penetrates the outer membrane by an additional non-porin p...

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Effects of Carbon Sources on Antibiotic Resistance in Pseudomonas aeruginosa

Cited by 27 publications

References 15 publications

Characterization of mechanisms of quinolone resistance in Pseudomonas aeruginosa strains isolated in vitro and in vivo during experimental endocarditis

Characterization of mechanisms of quinolone resistance in Pseudomonas aeruginosa strains isolated in vitro and in vivo during experimental endocarditis

Rethinking the Hierarchy of Sugar Utilization in Bacteria

Influence of growth media on Escherichia coli cell composition and ceftazidime susceptibility

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