Acceleration of protease effect on Staphylococcus aureus biofilm dispersal

Abstract

Bacterial biofilms are associated with the persistent infections because of their high tolerance to antimicrobial agents. Hence, controlling pathogenic biofilm formation is important in bacteria‐related diseases. Staphylococcus aureus is a versatile human pathogen that readily forms biofilms on human tissues and diverse medical devices. As S. aureus can be naturally found in multi‐species communities, the supernatants of 28 bacteria were screened to identify new biofilm inhibitory components against S. aureus. The culture supernatant (1%, v/v) of Pseudomonas aeruginosa PAO1 inhibited S. aureus biofilm formation more than 90% without affecting its planktonic cell growth. The P. aeruginosa supernatant contained a high protease activity, which both inhibited S. aureus biofilm formation and detached pre‐existing biofilms. An examination of 13 protease‐deficient P. aeruginosa mutants identified that LasB elastase is a major antibiofilm protease in P. aeruginosa against S. aureus. Transcriptional analyses showed that P. aeruginosa supernatant induced the expression of endogenous protease genes (aur, clp, scpA, splA, and sspA) and other regulatory genes (agrA, hla, and saeS). Additionally, exogenous proteinase K clearly enhanced the protease activity of S. aureus. Hence, S. aureus accelerated the expression of its own protease genes in the presence of exogenous protease, leading to the rapid dispersal of its biofilm.

Coculture of Staphylococcus aureus with Pseudomonas aeruginosa Drives S. aureus towards Fermentative Metabolism and Reduced Viability in a Cystic Fibrosis Model

“…Less dramatic biofilm dispersion similarly occurs on CFBE monolayers prior to the second medium change in the airway cell coculture system. This S. aureus biofilm dispersion phenomenon was previously reported by Park et al to be mediated by P. aeruginosa proteases (42). While the described S. aureus biofilm dispersion phenotype is consistent with the observations in our coculture model on plastic, other mechanisms leading to an increased planktonic population are possible.…”

“…This striking negative clinical correlation between S. aureus and P. aeruginosa during teenage years and young adulthood has driven several in vitro and in vivo studies geared toward characterizing the interbacterial interactions of these two organisms (36)(37)(38)(39)(40)(41)(42)(43)(44). These previous studies have found that P. aeruginosa secretes various antistaphylococcal products and proteases, such as LasA, that can cause both biofilm dispersion and cell lysis of S. aureus (42,45).…”

“…These previous studies have found that P. aeruginosa secretes various antistaphylococcal products and proteases, such as LasA, that can cause both biofilm dispersion and cell lysis of S. aureus (42,45). Further, P. aeruginosa produces several inhibitors of S. aureus respiration, including hydrogen cyanide, quinoline N-oxides, and the phenazine pyocyanin (41,(46)(47)(48).…”

Role of Extracellular Proteases in Biofilm Disruption of Gram Positive Bacteria with Special Emphasis on Staphylococcus aureus Biofilms

“…Park et al [36] also tested the supernatants of 28 bacteria to identify new anti-biofilm molecules against S. aureus. The culture supernatant (1% v/v) of Pseudomonas aeruginosa PAO1 inhibited biofilm formation by the test organism by more than 90% without affecting its planktonic cell growth.…”

“…The P. aeruginosa supernatant containing protease activity inhibited both biofilm formation and detached existing biofilms. Investigation using 13 protease-deficient P. aeruginosa mutants by Park et al helped showed that LasB elastase was the enzyme responsible for the anti-biofilm activity [36].…”