Outer membrane permeation of beta-lactam antibiotics in Escherichia coli, Proteus mirabilis, and Enterobacter cloacae.
Mutant strains lacking outer membrane protein(s) were isolated from Escherichia coli, Proteus mirabilis, and Enterobacter cloacae. The outer membrane protein(s) of P. mirabilis and E. cloacae corresponding to E. coli porin were identified on the basis of their function, namely, their ability to allow the permeation of glucose as demonstrated by [14C]glucose uptake by intact cells. P. mirabilis has only one outer membrane pore protein (molecular weight, 40,000), but E. cloacae has at least two such proteins (molecular weights, 37,000 and 39,000 to 40,000). When the bacteria lost these proteins or porin, the outer membrane permeation of cefazolin was found to be greatly reduced in these three species. Such a change in the outer membrane permeation closely correlated with a significant decrease in the bacterial susceptibility to cephalosporins, including cefoxitin. These results suggested that the main pathway for cephalosporin permeation is the pore made up of these proteins. The 39,000- to 40,000-molecular-weight protein in E. cloacae was also assumed to play an important role in the outer membrane permeation of tetracycline and chloramphenicol. On the other hand, the permeation route of penicillins was obscure. The susceptibility to penicillins, except in some cases, was little influenced by the absence of the proteins. Ampicillin was found to pass through the outer membrane via the same route as the cephalosporins, but the possibility that ampicillin and other penicillins possess another unknown route for outer membrane permeation could not be ruled out.
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000302:isolation & purification; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D002511:Cephalosporins / Q000378:metabolism; D004754:Enterobacter / Q000378:metabolism*; D004755:Enterobacteriaceae / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D009154:Mutation; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010458:Peptidyl Transferases; D011513:Proteus mirabilis / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase