Abstract
Antibiotics taken up into gram-negative bacteria face two major diffusion barriers, the outer and cytoplasmic membranes. Of these, the former has been most studied and is discussed in detail here. Evidence from antibiotic MIC studies on porin-deficient mutants compared with their porin-sufficient parent strains has provided strong support for the proposal that some antibiotics, particularly β-lactams, pass across the outer membrane through the water-filled channels of a class of proteins called porins. Nevertheless substantial evidence has accumulated for the importance of non-porin pathways of antibiotic uptake across the outer membranes of gram-negative bacteria. Examples discussed include the uptake of polycationic antibiotics via the self-promoted pathway, the uptake of hydrophobic antibiotics in some bacterial species and in mutants of others via the hydrophobic pathway, and the possible importance of poorly understood non-porin pathways of uptake of a variety of antibiotics. Other potential barriers to diffusion, including the cytoplasmic membrane, are briefly discussed.
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References
Hancock, R. E. W.: Aminoglycoside uptake and mode of action — with special reference to streptomycin and gentamicin. Journal of Antimicrobial Chemotherapy 1981, 8: 249–276.
Hancock, R. E. W.: Aminoglycoside uptake and mode of action — with special reference to streptomycin and gentamicin. Journal of Antimicrobial Chemotherapy 1981, 8: 429–445.
Nikaido, H., Vaara, M.: Molecular basis of bacterial outer membrane permeability. Microbiological Reviews 1985, 49:1–32.
Nikaido, H., Hancock, R. E. W.: Outer membrane permeability of Pseudomonas aeruginosa. In: Sokatch, J.R. (ed.): The bacteria: a treatise on structure and function, Volume 10. Academic Press, New York, 1985, p. 145 – 193.
Leive, L.: The barrier function of the gram-negative cell envelope. Annals of the New York Academy of Sciences 1974, 235: 109–127.
Hancock, R. E. W.: Model membrane studies of porin function. In: Inouye, M. (ed.): Bacterial outer membranes as model systems. John Wiley, New York, 1986, p. 187–225.
Nakae, T.: Identification of the major outer membrane protein of Escherichia coli that produces transmembrane channels in reconstituted vesicle membranes. Bio-chimica et Biophysica Acta 1976, 71: 877–884.
Zimmermann, W., Rosselet, A.: Function of the outer membrane of Escherichia coli as a permeability barrier to β-lactam antibiotics. Antimicrobial Agents and Chemotherapy 1977, 12: 368–372.
Nicas, T. I., Hancock, R. E. W.: Pseudomonas aeruginosa outer membrane permeability: isolation of a porin protein F-deficient mutant. Journal of Bacteriology 1983, 153: 281–285.
Mitsuyama, J., Hiruma, R., Yamaguchi, A., Sawai, T.: Identification of porins in outer membrane of Proteus, Morganella and Providencia spp. and their role in outer membrane permeation of β-lactams. Antimicrobial. Agents and Chemotherapy 1987, 31: 379–384.
Harder, K. J., Nikaido, H., Matsuhashi, M.: Mutants of Escherichia coli that are resistant to certain β-lactam compounds lack the OmpF porin. Antimicrobial Agents and Chemotherapy 1981, 20: 549–552.
Then, R. L., Angehrn, P.: Multiply resistant mutants of Enterobacter cloacae selected by β-lactam antibiotics. Antimicrobial Agents and Chemotherapy 1986, 30: 684–688.
Woodruff, W. A., Hancock, R. E. W.: Construction and characterization of Pseudomonas aeruginosa protein F-deficient mutants after in vitro and in vivo insertion mutagenesis of the cloned gene. Journal of Bacteriology 1988, 170: 2592–2598.
Godfrey, A. J., Bryan, L. E.: Penetration of β-lactams through Pseudomonas aeruginosa porin channels. Antimicrobial Agents and Chemotherapy 1987, 31: 1216 – 1221.
Hancock, R. E. W.: Role of porins in outer membrane permeability. Journal of Bacteriology 1987, 169: 929–933.
Siden, I., Boman, H.: Escherichia coli mutants with altered sensitivity to cecropin D. Journal of Bacteriology 1983, 154: 170–176.
Bedard, J., Wong, S., Bryan, L. E.: Accumulation of enoxacin by Escherichia coli and Bacillus subtilis. Antimicrobial Agents and Chemotherapy 1987, 31: 1348 – 1354.
Watanabe, N.-A., Nagasu, T., Katsu, K., Kitoh, K.: E-0702, a new cephalosporin, is incorporated into Escherichia coli cells via the tonB-dependent iron transport system. Antimicrobial Agents and Chemotherapy 1987, 31:497–504.
Pugsley, A. P., Zimmermann, W., Wehri, W.: Highly efficient uptake of a rifampycin derivative via the FhuA-tonB-dependent uptake route in Escherichia coli. Journal of General Microbiology 1987, 133: 3505–3511.
Quinn, J. P., Dudek, E. J., DiVincenzo, C. A., Lucks, D. A., Lerner, S. A.: Emergence of resistance to imi-penem during therapy for Pseudomonas aeruginosa infections. Journal of Infectious Diseases 1986, 289–294.
Hancock, R. E.W.: Alterations in outer membrane permeability. Annual Reviews of Microbiology 1984, 38: 237–264.
Rivera, M., Hancock, R. E. W., Sawyer, J. G., Haug, A., McGroarty, G. J.: Enhanced binding of polycationic antibiotics to lipopolysaccharide from an aminoglyco-side-supersusceptible tolA mutant strain of Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 1988, 32: 649–655.
Moore, R. A., Hancock, R. E. W.: Involvement of outer membrane of Pseudomonas cepacia in aminoglycoside and polymyxin resistance. Antimicrobial Agents and Chemotherapy 1986, 30: 923–926.
Martin, N. L., Beveridge, T. J.: Gentamicin interaction with Pseudomonas aeruginosa cell envelope. Antimicrobial Agents and Chemotherapy 1986, 29: 1079–1087.
Garrod, L. P., Lambert H. P., O’Grady, F.: Antibiotic and chemotherapy. Churchill Livingstone, Edinburgh, 1981.
Angus, B. L., Fyfe, J. A. M., Hancock, R.E.W.: Mapping and characterization of two mutations to antibiotic supersusceptibility in Pseudomonas aeruginosa. Journal of General Microbiology 1987, 133: 2905–2914.
Hinma, R., Yamaguchi, A., Sawai, T.: The effect of lipopolysaccharide on lipid bilayer permeability of β-lactam antibiotics. FEBS Letters 1984, 170: 268–272.
Rocque, W. J., Fesik, S.W., Haug, A., McGroarty, E. J.: Polycation binding to isolated lipopolysaccharide from antibiotic-hypersusceptible mutant strains of Escherichia coli. Antimicrobial Agents and Chemotherapy 1988, 32: 308–313.
Bryan, L. E.: Bacterial resistance and susceptibility to chemotherapeutic agents. Cambridge University Press, Cambridge, 1982.
Nichols, W. W.: On the mechanism of translocation of dihydrostreptomycin across the bacterial cytoplasmic membrane. Biochimica et Biophysica Acta 1987, 895: 11–23.
Chopra, I., Ball, P.: Transport of antibiotics into bacteria. Advances in Microbial Physiology 1982, 23: 183 – 240.
Scherrer, R., Gerhardt, P.: Molecular sieving by the Bacillus megaterium cell wall and protoplast. Journal of Bacteriology 1971, 107: 718–735.
Slack, M. P. E., Nichols, W. W.: Antibiotic penetration through bacterial capsules and exopolysaccharides. Journal of Antimicrobial Chemotherapy 1982, 10: 368–372.
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© 1989 Springer Fachmedien Wiesbaden
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Hancock, R.E.W., Bell, A. (1989). Antibiotic Uptake into Gram-Negative Bacteria. In: Jackson, G.G., Schlumberger, H.D., Zeiler, H.J. (eds) Perspectives in Antiinfective Therapy. Vieweg+Teubner Verlag, Wiesbaden. https://doi.org/10.1007/978-3-322-86064-4_5
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DOI: https://doi.org/10.1007/978-3-322-86064-4_5
Publisher Name: Vieweg+Teubner Verlag, Wiesbaden
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