Biomaterial Database

Roles of porin and beta-lactamase in beta-lactam resistance of Pseudomonas aeruginosa. 1988

R E Hancock, and W A Woodruff

Department of Microbiology, University of British Columbia, Vancouver, Canada.

Pseudomonas aeruginosa demonstrates high intrinsic resistance to most beta-lactam antibiotics. Two factors that are interrelated appear to be important in this intrinsic resistance: an inducible, chromosomally encoded type Id beta-lactamase and low outer-membrane permeability. beta-Lactamase-noninducible mutants are supersusceptible to many beta-lactam agents, whereas constitutively derepressed mutants are considerably more resistant even to so-called beta-lactamase-stable beta-lactams. For the latter mutants, by analysis of kinetics, it can be demonstrated that synergy between slow permeation across the outer membrane and slow hydrolysis of the beta-lactamase-stable beta-lactams can explain resistance. Wild-type P. aeruginosa allows outer membrane permeation of beta-lactam agents at rates 1%-8% of those measured for Escherichia coli. The majority of trans-outer-membrane channels formed by P. aeruginosa porin protein F are too small to allow passage of beta-lactam antibiotics. Nevertheless, this porin is apparently a conduit for beta-lactams, since protein F-deficient mutants have small changes in susceptibility to certain beta-lactam agents. This low outer-membrane permeability acting in synergy with beta-lactamase is probably responsible for intrinsic beta-lactam resistance in P. aeruginosa.

UI	MeSH Term	Description	Entries
D007473	Ion Channels	Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.	Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D011550	Pseudomonas aeruginosa	A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.	Bacillus aeruginosus,Bacillus pyocyaneus,Bacterium aeruginosum,Bacterium pyocyaneum,Micrococcus pyocyaneus,Pseudomonas polycolor,Pseudomonas pyocyanea
D002463	Cell Membrane Permeability	A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.	Permeability, Cell Membrane
D004352	Drug Resistance, Microbial	The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).	Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D000900	Anti-Bacterial Agents	Substances that inhibit the growth or reproduction of BACTERIA.	Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001425	Bacterial Outer Membrane Proteins	Proteins isolated from the outer membrane of Gram-negative bacteria.	OMP Proteins,Outer Membrane Proteins, Bacterial,Outer Membrane Lipoproteins, Bacterial
D001618	beta-Lactamases	Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins.	beta-Lactamase,beta Lactamase,beta Lactamases
D047090	beta-Lactams	Four-membered cyclic AMIDES, best known for the PENICILLINS based on a bicyclo-thiazolidine, as well as the CEPHALOSPORINS based on a bicyclo-thiazine, and including monocyclic MONOBACTAMS. The BETA-LACTAMASES hydrolyze the beta lactam ring, accounting for BETA-LACTAM RESISTANCE of infective bacteria.	beta-Lactam,4-Thia-1-Azabicyclo(3.2.0)Heptanes,4-Thia-1-Azabicyclo(4.2.0)Octanes,beta Lactam,beta Lactams
D018272	Porins	Porins are protein molecules that were originally found in the outer membrane of GRAM-NEGATIVE BACTERIA and that form multi-meric channels for the passive DIFFUSION of WATER; IONS; or other small molecules. Porins are present in bacterial CELL WALLS, as well as in plant, fungal, mammalian and other vertebrate CELL MEMBRANES and MITOCHONDRIAL MEMBRANES.	Pore Protein,Pore Proteins,Porin,Protein, Pore,Proteins, Pore