are very toxic to gram-positive bacteria (57, 230, 242). In enteric gram-negative bacteria, which live in the intestinal tract of animals, the outer membrane has developed into a very effective barrier, giving protection to cells from the detergent action of bile salts and degradation by digestive enzymes (207). At the same time the outer membrane of enteric and some other gram-negative bacteria acts as a strong permeability barrier to many antibiotics that are effective against other bacteria (e.g., macrolides, novobiocin, rifamycins, lincomycin, clindamycin, and fusidic acid; see reference 207). Even when the diffusion of antibiotic is merely slowed down by the presence of outer membrane, the bacteria can then inactivate the small amount of penetrating antibiotic rather than try to inactivate the almost infinite amount of antibiotic present in the medium, and thus very high levels of resistance are easily established in 1

No abstract

The outer membrane of gram-negative bacteria provides the cell with an effective permeability barrier against external noxious agents, including antibiotics, but is itself a target for antibacterial agents such as polycations and chelators. Both groups of agents weaken the molecular interactions of the lipopolysaccharide constituent of the outer membrane. Various polycations are able, at least under certain conditions, to bind to the anionic sites of lipopolysaccharide. Many of these disorganize and cross the outer membrane and render it permeable to drugs which permeate the intact membrane very poorly. These polycations include polymyxins and their derivatives, protamine, polymers of basic amino acids, compound 48/80, insect cecropins, reptilian magainins, various cationic leukocyte peptides (defensins, bactenecins, bactericidal/permeability-increasing protein, and others), aminoglycosides, and many more. However, the cationic character is not the sole determinant required for the permeabilizing activity, and therefore some of the agents are much more effective permeabilizers than others. They are useful tools in studies in which the poor permeability of the outer membrane poses problems. Some of them undoubtedly have a role as natural antibiotic substances, and they or their derivatives might have some potential as pharmaceutical agents in antibacterial therapy as well. Also, chelators (such as EDTA, nitrilotriacetic acid, and sodium hexametaphosphate), which disintegrate the outer membrane by removing Mg2+ and Ca2+, are effective and valuable permeabilizers.

No abstract

Lactobacilli and bifidobacteria are extremely rare causes of infection in humans, as are probiotics based on these organisms. This lack of pathogenicity extends across all age groups and to immunocompromised individuals. Strains used for new probiotics should be chosen from the commensal flora of humans and should not carry intrinsic resistance to antibiotics that would prevent treatment of a rare probiotic infection. Vigilance regarding the detection of possible rare cases of infection due to probiotics should be maintained, and isolates should be sent to reference centers for molecular characterization and confirmation.