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Molecular mechanisms involved in the transport of antibiotics into bacteria

Published online by Cambridge University Press:  23 August 2011

I. Chopra
I. Chopra
Affiliation:
Department of Microbiology, The Medical School, University of Bristol, Bristol BS8 1TD
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Summary

Many clinically useful antibacterial drugs have intracellular target sites. Therefore, in order to reach their targets, these compounds must be able to cross bacterial outer and cytoplasmic membranes. Considerable information is available on the mechanisms by which antibiotics cross bacterial membranes and, in many cases, it is now possible to define the molecular basis of their uptake. Passage of drugs across the outer membrane of Gram-negative bacteria can occur by diffusion through porin channels (e.g. β-lactams and tetracyclines), by facilitated diffusion using specific carriers (e.g. albomycin), or by self-promoted uptake (e.g. aminoglycosides and polymyxins). Transfer of antibiotics across the bacterial cytoplasmic membrane is usually mediated by active, carrier-mediated, transport systems normally operating to transport essential solutes into the cell. For example, the antibiotic streptozotocin bears sufficient structural resemblance to N-acetyl-D-glucosamine to be transported by the phosphoenolpyruvate : phosphotransferase system, and D-cycloserine is recognized by the D-alanine, proton motive force dependent transport system. However, in some cases (e.g. tetracycline) although carrier-mediated transport is implied by the observation that drug uptake is energy dependent, the nature of the membrane carrier(s) responsible is unknown. Knowledge acquired from studies on bacterial peptide transport has been successfully used to deliver (or smuggle) amino acid mimetics disguised as peptides into the bacterial cell. These amino acid mimetics, although often poorly transported in their own right, are frequently potent inhibitors of bacterial peptidoglycan or lipopolysaccharide synthesis once they have gained access to the interior of the cell.

Type
Research Article
Information
Parasitology , Volume 96 , supplement S1: Symposia of the British Society for Parasitology Volume 25 Molecular transfer across parasite membranes , January 1988 , pp. S25 - S44
Copyright
Copyright © Cambridge University Press 1988

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References

REFERENCES

Abdel-Sayed, S. (1987). Transport of chloramphenicol into sensitive strains of Escherichia coli and Pseudomonas aeruginosa. Journal of Antimicrobial Chemotherapy 19, 7–20.CrossRefGoogle ScholarPubMed
Ames, G. F-L. (1986). Bacterial periplasmic transport systems: structure, mechanism, and evolution. Annual Review of Biochemistry 55, 397–425.CrossRefGoogle ScholarPubMed
Argast, M. & Beck, C. F. (1984). Tetracycline diffuses through phospholipid bilayers and binds to phospholipids. Antimicrobial Agents and Chemotherapy 26, 263–5.CrossRefGoogle ScholarPubMed
Ashby, J., Piddock, L. J. V. & Wise, R. (1985). An investigation of the hydrophobicity of the quinolones. Journal of Antimicrobial Chemotherapy 16, 805–10.CrossRefGoogle ScholarPubMed
Brown, A. G. (1982). Beta-lactam nomenclature. Journal of Antimicrobial Chemotherapy 10, 365–8.CrossRefGoogle ScholarPubMed
Bryan, L. E. (1984). Aminoglycoside resistance. In Antimicrobial Drug Resistance (ed. Bryan, L. E.), pp. 241–277. New York: Academic Press.CrossRefGoogle Scholar
Bryan, L. E. & Van Den Elzen, H. M. (1977). Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria. Antimicrobial Agents and Chemotherapy 12, 163–77.CrossRefGoogle Scholar
Burns, J. L. & Smith, A. L. (1987). Chloramphenicol accumulation by Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 31, 686–90.CrossRefGoogle ScholarPubMed
Chopra, I. (1985). Mode of action of the tetracyclines and the nature of bacterial resistance to them. In Handbook of Experimental Pharmacology, vol. 78, (ed. Hlavka, J. J. and Boothe, J. H.), pp. 317–392. Berlin: Springer-Verlag.Google Scholar
Chopra, I. (1986). Transport of tetracyclines into E. coli requires a carboxamide group at the C2 position of the molecule. Journal of Antimicrobial Chemotherapy 18, 661–6.CrossRefGoogle ScholarPubMed
Chopra, I. & Ball, P. R. (1982). Transport of antibiotics into bacteria. Advances in Microbial Physiology 23, 183–240.CrossRefGoogle ScholarPubMed
Davies, J. E. (1986). Aminoglycoside–aminocyclitol antibiotics and their modifying enzymes. In Antibiotics in Laboratory Medicine, 2nd edn (ed. Lorian, V.), pp. 790–809. Baltimore: Williams and Wilkins.Google Scholar
Davis, B. D., Chen, L. & Tai, P. C. (1986). Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides. Proceedings of the National Academy of Sciences, USA 83, 6164–8.CrossRefGoogle ScholarPubMed
Dixon, R. A. & Chopra, I. (1986 a). Leakage of periplasmic proteins from Escherichia coli mediated by polymyxin B nonapeptide. Antimicrobial Agents and Chemotherapy 29, 781–8.CrossRefGoogle ScholarPubMed
Dixon, R. A. & Chopra, I. (1986 b). Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli. Journal of Antimicrobial Chemotherapy 18, 557–63.CrossRefGoogle ScholarPubMed
Gale, E. F., Cundliffe, E., Reynolds, P. E., Richmond, M. H. & Waring, M. J. (1981). The Molecular Basis of Antibiotic Action. London: Wiley Interscience.Google Scholar
Goldman, R., Kohlbrenner, W., Lartey, P. & Pernet, A. (1987). Antibacterial agents specifically inhibiting lipopolysaccharide synthesis. Nature, London 329, 162–4.CrossRefGoogle ScholarPubMed
Hammond, S. M., Lambert, P. A. & Rycroft, A. N. (1984). The Bacterial Cell Surface. London: Croom Helm.Google Scholar
Hammond, S. M., Claesson, A., Jansson, A. M., Larsson, L-G., Pring, B. G., Town, C. M. & Ekstrom, B. (1987). A new class of synthetic antibacterials acting on lipopolysaccharide biosynthesis. Nature, London 327, 730–2.CrossRefGoogle ScholarPubMed
Hancock, R. E. W. (1981 a). Aminoglycoside uptake and mode of action – with special reference to streptomycin and gentamicin. I. Antagonists and mutants. Journal of Antimicrobial Chemotherapy 8, 249–76.CrossRefGoogle ScholarPubMed
Hancock, R. E. W. (1981 b). Aminoglycoside uptake and mode of action – with special reference to streptomycin and gentamicin. II. Effects of aminoglycosides on cells. Journal of Antimicrobial Chemotherapy 8, 429–45.CrossRefGoogle ScholarPubMed
Hancock, R. E. W. (1984). Alterations in outer membrane permeability. Annual Review of Microbiology 38, 237–64.CrossRefGoogle ScholarPubMed
Hancock, R. E. W. (1987). Role of porins in outer membrane permeability. Journal of Bacteriology 169, 929–33.CrossRefGoogle ScholarPubMed
Henge, R. & Boos, W. (1983). Maltose and lactose transport in Escherichia coli. Examples of two different types of concentrative transport systems. Biochimica et Biophysica Acta 737, 443–78.CrossRefGoogle Scholar
Hirai, K., Aoyama, H., Irikura, T., Iyobe, S. & Mitsuhashi, S. (1986 a). Differences in susceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli. Antimicrobial Agents and Chemotherapy 29, 535–8.CrossRefGoogle ScholarPubMed
Hirai, K., Aoyama, H., Suzue, S., Irikura, T., Iyobe, S. & Mitsuhashi, S. (1986). Isolation and characterisation of norfloxacin-resistant mutants of Escherichia coli K-12. Antimicrobial Agents and Chemotherapy 30, 248–53.CrossRefGoogle ScholarPubMed
Lambert, M. P. & Neuhaus, F. C. (1972). Mechanism of D-cycloserine action: alanine racemase from Escherichia coli W. Journal of Bacteriology 110, 978–87.CrossRefGoogle ScholarPubMed
Levy, S. B. (1984). Resistance to the tetracyclines. In Antimicrobial Drug Resistance (ed. Bryan, L. E.), pp. 191–240. New York: Academic Press.CrossRefGoogle Scholar
McMurry, L. & Levy, S. B. (1978). Two transport systems for tetracycline in sensitive Escherichia coli: critical role for an initial rapid uptake system insensitive to energy inhibitors. Antimicrobial Agents and Chemotherapy 14, 201–9.CrossRefGoogle ScholarPubMed
Mitscher, L. A. (1978). The Chemistry of the Tetracycline Antibiotics. New York and Basel: Marcel Dekker.Google Scholar
Muir, M. E., Ballesteros, M. & Wallace, B. J. (1985). Respiration rate, growth rate and the accumulation of streptomycin in Escherichia coli. Journal of General Microbiology 131, 2573–9.Google ScholarPubMed
Nayler, J. H. C. (1987). Resistance to β-lactams in Gram-negative bacteria: relative contributions of β-lactamase and permeability limitations. Journal of Antimicrobial Chemotherapy 19, 713–32.CrossRefGoogle ScholarPubMed
Neuman, M. (1984). Recent developments in the field of phosphonic acid antibiotics. Journal of Antimicrobial Chemotherapy 14, 309–11.CrossRefGoogle ScholarPubMed
Nichols, W. W. (1988). On the mechanism of translocation of dihydrostreptomycin across the bacterial cytoplasmic membrane. Biochimica et Biophysica Acta (in the Press).Google Scholar
Nichols, W. W. & Young, S. N. (1985). Respiration-dependent uptake of dihydrostreptomycin by Escherichia coli. Its irreversible nature and lack of evidence for a uniport process. Biochemical Journal 228, 505–12.CrossRefGoogle ScholarPubMed
Nikaido, H. (1985). Role of permeability barriers in resistance to beta-lactam antibiotics. Pharmacology and Therapeutics 27, 197–231.CrossRefGoogle ScholarPubMed
Nikaido, H. & Nakae, T. (1979). The outer membrane of Gram-negative bacteria. Advances in Microbial Physiology 20, 163–250.CrossRefGoogle ScholarPubMed
Nikaido, H. & Vaara, T. (1985). Molecular basis of bacterial outer membrane permeability. Microbiological Reviews 49, 1–32.CrossRefGoogle ScholarPubMed
Nuesch, J. & Knusel, F. (1967). Sideromycins. In Antibiotics, Mechanism of Action, vol. 1 (ed. Gottlieb, D. and Shaw, P. D.), pp. 499–541. Berlin: Springer-Verlag.Google Scholar
Piddock, L. J. V. & Wise, R. (1986). The effect of altered porin expression in Escherichia coli upon susceptibility to 4-quinolones. Journal of Antimicrobial Chemotherapy 18, 547–8.CrossRefGoogle ScholarPubMed
Postma, P. W. & Lengeler, J. W. (1985). Phosphoenolpyruvate: carbohydrate phosphotransferase system of bacteria. Microbiological Reviews 49, 232–69.CrossRefGoogle ScholarPubMed
Reusser, F. (1971). Mode of action of streptozotocin. Journal of Bacteriology 105, 580–8.CrossRefGoogle ScholarPubMed
Reynolds, P. E. (1985). Inhibitors of bacterial cell wall synthesis. In The Scientific Basis of Antimicrobial Chemotherapy, 38th Symposium of the Society for General Microbiology (ed. Greenwood, D. and O'Grady, F.), pp. 13–10. Cambridge: Cambridge University Press.Google Scholar
Rick, D. & Osborn, M. J. (1972). Isolation of a mutant of Salmonella typhimurium dependent on D-arabinose-5-phosphate for growth and synthesis of 3-deoxy-D-mannoctulosonate (ketodeoxyoctonate). Proceedings of the National Academy of Sciences, USA 69, 3756–60.CrossRefGoogle ScholarPubMed
Ringrose, P. S. (1980). Peptides as antimicrobial agents. In Micro-organisms and Nitrogen Sources (ed. Payne, J. W.), pp. 641–692. London: John Wiley and Sons.Google Scholar
Ringrose, P. S. (1985). Warhead delivery and suicide substrates as concepts in antimicrobial drug design. In The Scientific Basis of Antimicrobial Chemotherapy, 38th Symposium of the Society for General Microbiology (ed. Greenwood, D. and O'Grady, F.), pp. 219–66. Cambridge: Cambridge University Press.Google Scholar
Rogers, H. J.Perkins, H. R. & Ward, J. B. (1980). Microbial Cell Walls and Membranes. London: Chapman & Hall.CrossRefGoogle Scholar
Rosen, B. P. (1986). Recent advances in bacterial ion transport. Annual Review of Microbiology 40, 263–86.CrossRefGoogle ScholarPubMed
Rosen, B. P. & Kashket, E. R. (1978). Energetics of active transport. In Bacterial Transport (ed. Rosen, B. P.), pp. 559–620. New York, Basel: Marcel Dekker.Google Scholar
Smith, J. T. (1985). The 4-quinolone antibacterials. In The Scientific Basis of Antimicrobial Chemotherapy, 38th Symposium of the Society for General Microbiology (ed. Greenwood, D. and O'Grady, F.), pp. 69–94. Cambridge: Cambridge University Press.Google Scholar
Smith, M. C. M. & Chopra, I. (1984). Energetics of tetracycline transport into Escherichia coli. Antimicrobial Agents and Chemotherapy 25, 446–9.CrossRefGoogle ScholarPubMed
Spratt, B. G. (1983). Penicillin binding proteins and the future of β-lactam antibiotics. Journal of General Microbiology 129, 1247–60.Google ScholarPubMed
Storm, D. R., Rosenthal, K. S. & Swanson, P. E. (1977). Polymyxin and related peptide antibiotics. Annual Review of Biochemistry 46, 723–63.CrossRefGoogle ScholarPubMed
Tomasz, A. (1983). Mode of action of β-lactam antibiotics – a microbiologist's view. In Antibiotics Containing the β-lactam Structure, Handbook of Experimental Pharmacology, vol. 67 (ed. Demain, A. L. and Solomon, N. A.), pp. 15–97. Berlin: Springer-Verlag.Google Scholar
Watanabe, N-A., Nagasu, T., Katsu, K. & Kitoh, K. (1987). E-0702, a new cephalosporin, is incorporated into Escherichia coli cells via the tonB-dependent iron transport system. Antimicrobial Agents and Chemotherapy 31, 497–504.CrossRefGoogle ScholarPubMed
Zenilman, J. M., Miller, M. H. & Mandel, L. J. (1986). In vitro studies simultaneously examining effect of oxacillin on uptake of radiolabelled streptomycin and on associated bacterial lethality in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 30, 877–82.CrossRefGoogle ScholarPubMed