Antibiotic uptake and transport by bacteria.
A few antibiotics, e.g. polymyxins, disorganize the bacterial wall. For most, however, the wall is an obstacle to be crossed. The extent of this barrier varies with the target to be reached, the drug and the bacterial species. Staphylococci and streptococci have only capsular material and peptidoglycan external to the cytoplasmic membrane (CM). These components afford little shielding and agents with targets on the outer surface of the CM (e.g. vancomycin and beta-lactams) have unhindered target access. Antibiotics with cytoplasmic or ribosomal targets must however cross the CM, usually by active transport. Mycobacteria have outer barriers beyond the CM, as do Gram-negative species. The latter organisms have an outer membrane (OM) located externally to the peptidoglycan and CM. Being hydrophilic, most antibiotics cross the OM by passive diffusion through pores composed of 'porin' proteins. Uptake varies with the drug's charge, size and hydrophilicity, also with the number of pores. Antibiotics larger than 800 D are excluded. Once across the OM, the antibiotics have access to the CM, which must be crossed by those with ribosomal or cytoplasmic targets. Resistance can arise by porin loss, or by loss of an active uptake pathway in the CM. Often the barrier is not absolute: rather uptake is reduced relative to drug removal or detoxification. Occasionally, e.g. with tetracyclines, resistance entails drug excretion or 'coating' of the ribosome.
Livermore
D M
DM
Department of Medical Microbiology, London Hospital Medical College, UK.
D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D002473:Cell Wall / Q000378:metabolism; D004058:Diffusion
D000900:Anti-Bacterial Agents