title: Outer membrane proteins responsible for the penetration of beta-lactams and quinolones in Pseudomonas aeruginosa.
abstract: Porin-deficient mutants of Pseudomonas aeruginosa PAO1 were selected by isolating latamoxef-resistant mutants following chemical mutagenesis. Highly latamoxef-resistant mutants had alterations in both the outer membrane proteins and penicillin-binding protein 3, a lethal target of latamoxef. Both of these alterations may be essential for cells to acquire high resistance to latamoxef. Many of the latamoxef-resistant mutants were also resistant to new quinolones and chloramphenicol. Resistance to these compounds was simultaneously co-transduced from one mutant into strain PAO1 when selection was made for transduction of ofloxacin resistance. Study of these transductants indicated that decreased amounts of outer membrane proteins C, D2, E1, and E2 lowered the outer membrane permeability and resulted in resistance. Three of these proteins were apparently identical to proteins previously reported to function as small pores. The results suggested that at least one of the four proteins was functioning as a porin for the antibacterial agents studied.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamano
authors.forename: T
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Komatsu
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D006602:Hexosyltransferases / Q000378:metabolism; D006801:Humans; D009070:Moxalactam / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism; D002267:Muramoylpentapeptide Carboxypeptidase; D009154:Mutation / Q000235:genetics; D015242:Ofloxacin / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D015242:Ofloxacin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D009070:Moxalactam