salicylates and Pseudomonas-Infections

Three types of multiple-drug-resistant mutants which were phenotypically similar to previously described nalB, nfxB, and nfxC mutants were isolated from Pseudomonas aeruginosa PAO1 and two clinical isolates. Type 1 (nalB-type) mutants showed cross-resistance to meropenem, cephems, and quinolones. They overproduced an outer membrane protein with an apparent molecular mass of 50 kDa (OprM). Type 2 (nfxB-type) mutants showed cross-resistance to quinolones and new cephems, i.e., cefpirome and cefozopran, concomitant with overproduction of an outer membrane protein with an apparent molecular mass of 54 kDa (OprJ). Type 3 (nfxC-type) mutants showed cross-resistance to carbapenems and quinolones. They produced decreased amounts of OprD and increased amounts of a 50-kDa protein (OprN), which was almost the same molecular weight as that of OprM, but it was distinguishable from OprM by its heat modifiability on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of salicylate, the parent strains showed an increased level of resistance to carbapenems and quinolones and produced decreased amounts of OprD and increased amounts of OprN. Salicylate caused the repression of OprJ production and the loss of resistance to cefpirome and cefozopran in two of the three OprJ-overproducing mutants, although salicylate slightly increased the level of resistance in the parent strains. The changes in susceptibilities were transient in the presence of salicylate. These data suggest that at least three different outer membrane proteins, OprM, OprJ, and OprN, are associated with multiple drug resistance in P. aeruginosa.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Carbapenems; Drug Resistance, Multiple; Electrophoresis, Polyacrylamide Gel; Humans; Microbial Sensitivity Tests; Molecular Weight; Phenotype; Pseudomonas aeruginosa; Pseudomonas Infections; Salicylates; Salicylic Acid

Various inflammatory agents, including Pseudomonas aeruginosa, bacterial filtrates, endotoxin, and phorbol myristate acetate were found to induce significant increases in corneal chemiluminescense (CLM). Disruption of polymorphonuclear leukocytes within corneas by sonication, freeze-thawing or cryotherapy, or reduction of corneal infiltration by induction of neutropenia resulted in marked decreases of CLM. Increased corneal CLM was associated with significant increases in corneal thickness and water content. Oxygen-free radical scavengers significantly inhibited CLM of experimentally infected corneas in vitro, as did the anti-inflammatory agents prednisolone acetate, indomethacin, and salicylic acid. In vivo therapy of infected corneas with prednisolone resulted in significant reductions in corneal CLM, thickness, and water content compared with saline-treated eyes. The CLM assay is a simple technique that allows quantitation of corneal inflammation and evaluation of the effect of therapeutic agents on corneal inflammation.

Topics: Animals; Cornea; Cryosurgery; Endotoxins; Escherichia coli; Guinea Pigs; Keratitis; Luminescent Measurements; Luminol; Mannitol; Neutrophils; Prednisolone; Pseudomonas aeruginosa; Pseudomonas Infections; Salicylates; Sodium Hydroxide; Tetradecanoylphorbol Acetate

Topics: Atropine; Benzalkonium Compounds; Biguanides; Chlorobutanol; Cresols; Hot Temperature; Mercury; Ophthalmic Solutions; Organometallic Compounds; Pharmaceutic Aids; Physostigmine; Pilocarpine; Pseudomonas aeruginosa; Pseudomonas Infections; Salicylates