Bacterial antibiotic efflux systems of medical importance

Abstract

Multidrug efflux systems endow on bacterial cells the ability to limit the access of antimicrobial agents to their targets. By actively pumping out antibiotic molecules, these systems prevent the intracellular accumulation necessary for antibiotics to exert their lethal activity. Drug efflux appears to be one of the most widespread antibiotic resistance mechanisms among microorganisms, since it has been demonstrated to occur in many Gram-positive and Gram-negative bacteria including medically important species like staphylococci, streptococci, enterobacteria and opportunistic pathogens like Pseudomonas aeruginosa. Efflux pumps can be specific for only one substrate or accommodate a more or less wide range of noxious products. Export of structurally unrelated compounds confers a multidrug-resistance phenotype on bacterial cells. Therapeutically critical levels of resistance can be achieved by overexpression of efflux systems, especially in those species such as P. aeruginosa which possess a low outer membrane permeability. It is suspected that the dual physiological function of active efflux systems is both the secretion of intracellular metabolites and the protection against a variety of harmful substances that the microorganism may encounter in its natural environment.

Characterization of Inhibitor-Resistant Histone Deacetylase Activity in Plant-Pathogenic Fungi

“…Two fungi that produce other HDAC inhibitors were also tested. A. brassicicola, a pathogen of Brassica species, produces depudecin (32). D. chlamydosporia, a soil saprophyte and pathogen of nematode eggs, produces a cyclic peptide, chlamydocin, related to HC-toxin (13,48).…”

“…Known self-protection mechanisms of microorganisms include intracellular modification of the compound to a less toxic form, posttranslational modification of the enzyme target site, synthesis of a novel insensitive form of the target site, and secretion pumps and carriers for removing the compound from the cell (10,17,21,25,32,42). Plant-pathogenic microorganisms produce toxic secondary metabolites, and a number of these are phytotoxins with established roles in determining host range, virulence, and symptom development (8,20,29,46,51).…”

Inhibition of Antibiotic Efflux in Bacteria by the Novel Multidrug Resistance Inhibitors Biricodar (VX-710) and Timcodar (VX-853)

“…While permeability is a significant barrier to antibiotics in gram-negative bacteria due to the presence of an outer membrane, it is an unlikely mechanism of resistance for grampositive bacteria, since they lack an outer membrane. Efflux of antibiotics is a clinically significant general resistance mechanism for bacteria, often endowing organisms with multipledrug-resistant (MDR) phenotypes (14). Gram-positive and gram-negative bacteria can possess multiple chromosomal and plasmid-encoded efflux pumps with broad substrate specificities, including both naturally and synthetically produced antibiotics (2,24,30).…”

Pseudomonas and Proteus: Partial Purification and Characterization of Antibacterial Protein: A Review

“…Furthermore, along with the deep studies of marine natural products biosynthesis, some evidence indicates that many bioactive compounds previously found in marine animals and plants were produced or metabolized by associated microorganisms (Carte et al, 1996;Kohler et al, 1999;Osinga et al, 2001;Rinehart, 2000;Sponga et al, 1999).…”