Milestone in eradicating Pseudomonas biofilms

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An important piece of research was published this week about fighting Pseudomonas biofilms. Specifically, a team built a small molecule that disrupts such biofilms, returning bacteria to their free-floating (=planktonic) state. When this compound is used in combination with the usual anti-Pseudomonas antibiotics, such as Ciprofloxacin + Gentamycin combined, a Pseudomonas biofilm may be entirely eradicated. Now, the next step is to see if mice can tolerate it.-------------Antimicrob Agents Chemother. 2011 Mar 28. [Epub ahead of print]Novel Inhibitors Of The Pseudomonas aeruginosa Virulence Factor Pseudolysin/LasB: A Potential Therapeutic Approach For The Attenuation Of Virulence Mechanisms In Pseudomonal Infection.Cathcart GR, Quinn D, Greer B, Harriott P, Lynas JF, Gilmore BF, B.School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast. BT9 7BL; and Department of Biological Sciences, Medical Biology Centre, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL.AbstractPseudomonas elastase (LasB), a metalloprotease virulence factor, is known to play a pivotal role in pseudomonal infection. LasB is secreted at the site of infection where it exerts a proteolytic action that spans from broad tissue destruction to subtle action on components of the host immune system. The former enhances invasiveness by liberating nutrients for continued growth, while the latter exerts an immunomodulatory effect, manipulating the normal immune response. In addition to the extracellular effects of secreted LasB, it also acts within the bacterial cell to trigger the intracellular pathway that initiates growth as a bacterial biofilm. The key role of LasB in pseudomonal virulence makes it a potential target for the development of an inhibitor as an antimicrobial agent. The concept of inhibition of virulence is a recently established antimicrobial strategy, and such agents have been termed 'second-generation' antibiotics. This approach holds promise in that it seeks to attenuate virulence processes without bactericidal action, and hence without selection pressure for the emergence of resistant strains. A potent inhibitor of LasB, N-mercaptoacetyl-Phe-Tyr-amide (Ki = 41 nM) has been developed, and its ability to block these virulence processes has been assessed. It has been demonstrated that this compound can completely block the action of LasB on protein targets that are instrumental in biofilm formation and immunomodulation. The novel LasB inhibitor has also been employed in bacterial cell-based assays, to reduce the growth of pseudomonal biofilms, and to eradicate biofilm completely, when used in combination with conventional antibiotics.