Browsing by Author "O'Toole, George A."

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Biofilms strike back
(2005-11) O'Toole, George A.; Stewart, Philip S.
Excessive use of antibiotics has increased resistance of many microbes to these drugs. In a recent issue of Nature, Hoffman et al.1 show that too little antibiotic can also be detrimental. They demonstrated that subinhibitory levels of the aminoglycoside-class antibiotic tobramycin increase biofilm formation by various isolates of the bacterial pathogen Pseudomonas aeruginosa. This finding may lead to new therapies against persistent infections stemming from biofilm formation.
A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance
(2003-11) Mah, Thien-Fah; Pitts, Betsey; Pellock, Brett; Walker, Graham C.; Stewart, Philip S.; O'Toole, George A.
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.
Micro-patterned surfaces reduce bacterial colonization and biofilm formation in vitro: Potential for enhancing endotracheal tube designs
(2014-04) May, Rhea M.; Hoffman, Matt G.; Sogo, M.; Parker, Albert E.; O'Toole, George A.; Brennan, Anthony B.; Reddy, Shravanthi T.
Ventilator-associated pneumonia (VAP) is a leading hospital acquired infection in intensive care units despite improved patient care practices and advancements in endotracheal tube (ETT) designs. The ETT provides a conduit for bacterial access to the lower respiratory tract and a substratum for biofilm formation, both of which lead to VAP. A novel microscopic ordered surface topography, the Sharklet micro-pattern, has been shown to decrease surface attachment of numerous microorganisms, and may provide an alternative strategy for VAP prevention if included on the surface of an ETT. To evaluate the feasibility of this micro-pattern for this application, the microbial range of performance was investigated in addition to biofilm studies with and without a mucin-rich medium to simulate the tracheal environment in vitro.