Alginate lyase exhibits catalysis-independent biofilm dispersion and antibiotic synergy.
More than 2 decades of study support the hypothesis that alginate lyases are promising therapeutic candidates for treating mucoid Pseudomonas aeruginosa infections. In particular, the enzymes' ability to degrade alginate, a key component of mucoid biofilm matrix, has been the presumed mechanism by which they disrupt biofilms and enhance antibiotic efficacy. The systematic studies reported here show that, in an in vitro model, alginate lyase dispersion of P. aeruginosa biofilms and enzyme synergy with tobramycin are completely decoupled from catalytic activity. In fact, equivalent antibiofilm effects can be achieved with bovine serum albumin or simple amino acids. These results provide new insights into potential mechanisms of alginate lyase therapeutic activity, and they should motivate a careful reexamination of the fundamental assumptions underlying interest in enzymatic biofilm dispersion.
Thayer School of Engineering, Dartmouth, Hanover, New Hampshire, USA.
John W
JW
Lamppa
Karl E
KE
Griswold
D000464:Alginates / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D004338:Drug Combinations; D004357:Drug Synergism; D004926:Escherichia coli / Q000235:genetics; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D011133:Polysaccharide-Lyases / Q000235:genetics / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014031:Tobramycin / Q000494:pharmacology*
D000464:Alginates; D000596:Amino Acids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004338:Drug Combinations; D006603:Hexuronic Acids; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine; D020723:Glucuronic Acid; D011133:Polysaccharide-Lyases; C016158:poly(beta-D-mannuronate) lyase; D014031:Tobramycin