Bacteriolytic effect of membrane vesicles from Pseudomonas aeruginosa on other bacteria including pathogens: conceptually new antibiotics

Abstract

Pseudomonas aeruginosa releases membrane vesicles (MVs) filled with periplasmic components during normal growth, and the quantity of these vesicles can be increased by brief exposure to gentamicin. Natural and gentamicin-induced membrane vesicles (n-MVs and g-MVs, respectively) are subtly different from one another, but both contain several important virulence factors, including hydrolytic enzyme factors (J. L. Kadurugamuwa and T. J. Beveridge, J. Bacteriol. 177:3998-4008, 1995). Peptidoglycan hydrolases (autolysins) were detected in both MV types, especially a periplasmic 26-kDa autolysin whose expression has been related to growth phase (Z. Li, A. J. Clarke, and T. J. Beveridge, J. Bacteriol. 178:2479-2488, 1996). g-MVs possessed slightly higher autolysin activity and, at the same time, small quantities of gentamicin. Both MV types hydrolyzed isolated gram-positive and gram-negative murein sacculi and were also capable of hydrolyzing several glycyl peptides. Because the MVs were bilayered, they readily fused with the outer membrane of gram-negative bacteria. They also adhered to the cell wall of gram-positive bacteria. g-MVs were more effective in lysing other bacteria because, in addition to the autolysins, they also contained small amounts of gentamicin. The bactericidal activity was 2.5 times the MIC of gentamicin, which demonstrates the synergistic effect of the antibiotic with the autolysins. n-MVs were capable of killing cultures of P. aeruginosa with permeability resistance against gentamicin, indicating that the fusion of n-MV to the outer membrane liberated autolysins into the periplasm, where they degraded the peptidoglycan and lysed the cells. g-MVs had even greater killing power since they liberated both gentamicin and autolysins into these resistant cells. These findings may help develop a conceptually new group of antibiotics designed to be effective against hard-to-kill bacteria.

Predatory activity of Myxococcus xanthus outer-membrane vesicles and properties of their hydrolase cargo

“…The addition of GAPDH stimulated killing of E. coli by mxOMVs, suggesting that predatory activity was mediated by fusion with the E. coli membrane, as suggested for OMVs of Pseudomonas aeruginosa (Kadurugamuwa & Beveridge, 1996). The lytic activity of mxOMVs is lost upon French-pressing (and French-pressed cells also have no lytic activity), indicating that lytic activity is not just a consequence of being 'membranous' but also requires an enclosed, intact membrane.…”

The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureus

“…In P. aeruginosa, eDNA release depends on quorum sensing (35), and there is evidence to suggest that cell lysis itself may be achieved by prophage induction within a biofilm (38,50), or alternatively, as a consequence of the release of membrane vesicles that contain bacteriolytic activity (51,52) as well as DNA (53). In Streptococcus mutans and Streptococcus pneumoniae, DNA is released from a lysing subfraction of the bacterial population in response to competence development, a physiological process that also depends on quorum sensing (54)(55)(56)(57)(58)(59).…”

Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins

“…Recently, eukaryotic pathogens, such as Cryptococcus neoformans, have been found to release virulence factors in vesicles, suggesting that this is a widely used strategy for pathogenic microbes to deliver a noxious cargo to target immune cells (12,13). Many Gram-negative pathogenic bacterial species, including Pseudomonas aeruginosa, produce vesicles that contain toxins or other virulence factors and, in several cases, vesicles have been proposed to be vehicles for toxin delivery to eukaryotic cells (14)(15)(16)(17). Significantly less is known about the role of vesicular formation for Gram-positive bacteria.…”