Biofilm Disruption and increased sensitivity to Colistin?

A new study demonstrates two enzymes that are capable of disrupting Pseudomonas biofilm and increasing sensitivity to colistin

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Lynne Howell and colleagues at UCLA are "weaponising bacteria against themselves". They took glycoside hydrolases from Pseudomonas and used them to disrupt their own biofilms.

There are several interesting findings to this paper:

- The glycoside hydrolases can prevent biofilm formation but also disrupt pre-existing biofilms

- The use of glycoside hydrolases increased the sensitivity of the bacterial cells to colistin, the last resort antibiotic that has been the cause of may "antibiotic apocalypse" headlines over the last few weeks.

- Glycoside hydrolases also increased neutrophil killing of the bacterial cells.

While the use of biofilm disrupting compounds in clinical use is far from straight forward and can often make infections worse, the potential use in conjunction with antibiotics is attractive in the light of growing levels of multiresistant bacteria.

Article Details:

Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms

Perrin Baker, Preston J. Hill, Brendan D. Snarr, Noor Alnabelseya, Matthew J. Pestrak, Mark J. Lee, Laura K. Jennings, John Tam, Roman A. Melnyk, Matthew R. Parsek, Donald C. Sheppard, Daniel J. Wozniak and P. Lynne Howell


Bacterial biofilms present a significant medical challenge because they are recalcitrant to current therapeutic regimes. A key component of biofilm formation in the opportunistic human pathogen Pseudomonas aeruginosa is the biosynthesis of the exopolysaccharides Pel and Psl, which are involved in the formation and maintenance of the structural biofilm scaffold and protection against antimicrobials and host defenses. Given that the glycoside hydrolases PelAh and PslGh encoded in the pel and psl biosynthetic operons, respectively, are utilized for in vivo exopolysaccharide processing, we reasoned that these would provide specificity to target P. aeruginosa biofilms. Evaluating these enzymes as potential therapeutics, we demonstrate that these glycoside hydrolases selectively target and degrade the exopolysaccharide component of the biofilm matrix. PelAh and PslGh inhibit biofilm formation over a 24-hour period with a half maximal effective concentration (EC50) of 69.3 ± 1.2 and 4.1 ± 1.1 nM, respectively, and are capable of disrupting preexisting biofilms in 1 hour with EC50 of 35.7 ± 1.1 and 12.9 ± 1.1 nM, respectively. This treatment was effective against clinical and environmental P. aeruginosa isolates and reduced biofilm biomass by 58 to 94%. These noncytotoxic enzymes potentiated antibiotics because the addition of either enzyme to a sublethal concentration of colistin reduced viable bacterial counts by 2.5 orders of magnitude when used either prophylactically or on established 24-hour biofilms. In addition, PelAh was able to increase neutrophil killing by ~50%. This work illustrates the feasibility and benefits of using bacterial exopolysaccharide biosynthetic glycoside hydrolases to develop novel antibiofilm therapeutics.

Science Advances 20 May 2016:
Vol. 2, no. 5, e1501632
DOI: 10.1126/sciadv.1501632

Ben Libberton

Science Communicator, Freelance

I'm a freelance science communicator, formerly a Postdoc in the biofilm field. I'm interested in how bacteria cause disease and look to technology to produce novel tools to study and ultimately prevent infection.