Alginate Lyase Exhibits Catalysis-Independent Biofilm Dispersion and Antibiotic Synergy

Abstract

ABSTRACTMore than 2 decades of study support the hypothesis that alginate lyases are promising therapeutic candidates for treating mucoidPseudomonas aeruginosainfections. 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 anin vitromodel, alginate lyase dispersion ofP. aeruginosabiofilms 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.