A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance

Abstract

Biofilms are surface-attached microbial communities with characteristic architecture and phenotypic and biochemical properties distinct from their free-swimming, planktonic counterparts. One of the best-known of these biofilm-specific properties is the development of antibiotic resistance that can be up to 1,000-fold greater than planktonic cells. We report a genetic determinant of this high-level resistance in the Gram-negative opportunistic pathogen, Pseudomonas aeruginosa. We have identified a mutant of P. aeruginosa that, while still capable of forming biofilms with the characteristic P. aeruginosa architecture, does not develop high-level biofilm-specific resistance to three different classes of antibiotics. The locus identified in our screen, ndvB, is required for the synthesis of periplasmic glucans. Our discovery that these periplasmic glucans interact physically with tobramycin suggests that these glucose polymers may prevent antibiotics from reaching their sites of action by sequestering these antimicrobial agents in the periplasm. Our results indicate that biofilms themselves are not simply a diffusion barrier to these antibiotics, but rather that bacteria within these microbial communities employ distinct mechanisms to resist the action of antimicrobial agents.

Study of free oligosaccharides derived from the bacterial N -glycosylation pathway

“…(37,38), reduce flagella assembly, and increase sensitivity to antibiotics and detergents (in Rhizobium and Agrobacterium sp and P. aeruginosa) (4,39,40), and to have pleiotropic effects on polysaccharide biosynthesis, protein folding and degradation, and carbohydrate catabolism (in Erwinia chrysanthemi) (41). Loss of periplasmic glucan production in R. meliloti and Bradyrhizobium japonicum affected growth in various hypoosmotic environments (42,43), whereas the opposite effect, decreased growth rates in a hyperosmotic high sodium chloride environment was observed for the C. jejuni pglB, pglE, and pglF mutants where no detectable fOS was present.…”

Isolation and characterisation of silver(I) complexes of substituted coumarin-4-carboxylates which are effective against Pseudomonas aeruginosa biofilms

“…The antibacterial mechanism of silver ions has been well studied and it is possible that in these studies the silver complexes act by disrupting the signal processes associated with biofilm formation as the mechanisms involved in biofilm resistance to antimicrobials may differ from those responsible for antimicrobial resistance in planktonic bacteria. Biofilm resistance is multifactorial and includes a diffusion barrier, sequestration of antibiotics within the glucan polymers, slower growth, reduced oxygen concentrations at the base of the biofilm [52,53]. As such only a combination of different mechanisms could account for the levels of resistance seen in biofilm communities [54].…”

Biofilm streamers cause catastrophic disruption of flow with consequences for environmental and medical systems

“…Although biofilms are desirable in waste-water treatment (6), biofilms primarily cause undesirable effects such as chronic infections or clogging of industrial flow systems (1-3). Cells in biofilms display many behavioral differences from planktonic cells, such as a 1,000-fold increase in tolerance to antibiotics (7,8), an altered transcriptome (9-11), and spatially heterogeneous metabolic activity (12, 13). Some of these physiological peculiarities of biofilm-dwelling cells may be due to strong gradients of nutrients and metabolites, which also affect biofilm morphology and composition (14, 15).…”