Pseudomonas aeruginosa (PA14) infections lead to a high mortality rate for immunocompromised and cystic fibrosis patients due to their ability to form biofilms (BF). These BFs can survive against host immune systems and are difficult to eradicate with antibiotics due to high tolerance to antibiotics. The resilient alginate-based EPS matrix and the rhamnolipid interior shield are the key factors which disable the immune therapy and antibiotic treatments. The alginate and the rhamnolipid shield together with quorum sensing (QS) systems, protect the internal colonies of PA bacteria. Therefore, synergistic therapy with a QS inhibitor (QSI) which interferes with the BF forming bacteria can thus complement antibiotics. A mesoporous nanoassembly loaded with an antibiotic (Tobramycin) and QSI (Cinnamaldehyde) is coated with a rhamnolipid (Rh) liposome layer and tagged with the enzyme alginate lyase (AL) ((MSN@Q@Tob)Rh-AL) to degrade the alginate outer layer and migrate through the rhamnolipid shield to the interior BF core to deliver antibiotic and quorum sensing inhibitor to eradicate BF forming bacteria. The mesoporous silica core facilitated the loading of QSI and the negatively charged surface supported the interaction with cationic antibiotic. The nanoparticles coated with Rh liposomes and tagged with AL showed increased penetration (89%) through the depth of the BF. In the vicinity of the BF bacteria the Rh liposome layer has been degraded due to the bacteria secreted lipases and released around 75% of Tob and 52% of QSI in about 24 hours. Furthermore, the final nanoassembly showed higher BF formation inhibitory effects and higher BF degradation effects (68% ± 0.6 and 51% ± 0.8 respectively) compared to free antibiotic. This synthesized novel nanoassembly was succeeded in eradicating P. aeruginosa BFs grown in mammalian cells without causing any cytotoxic damage to the cells. This study offers a viable combinational therapy platform to be used in eradication other similar BFs.

Alginate lyase guided rhamnolipid coated mesoporous nanoassembly for synergistic delivery of an antibiotic and a quorum sensing inhibitor for the eradication of <i>Pseudomonas aeruginosa</i> biofilms

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Alginate lyase guided rhamnolipid coated mesoporous nanoassembly for synergistic delivery of an antibiotic and a quorum sensing inhibitor for the eradication of Pseudomonas aeruginosa biofilms