Combating virulence of Gram-negative bacilli by OmpA inhibition.
Xavier Vila-FarrésRaquel Parra-MillánViviana Sánchez-EncinalesMonica VareseRafael Ayerbe-AlgabaNuria BayóSalvador GuardiolaMaría Eugenia Pachón-IbáñezMartin KotevJesús GarcíaMeritxell TeixidóJordi VilaJerónimo PachónErnest GiraltYounes SmaniPublished in: Scientific reports (2017)
Preventing the adhesion of pathogens to host cells provides an innovative approach to tackling multidrug-resistant bacteria. In this regard, the identification of outer membrane protein A (OmpA) as a key bacterial virulence factor has been a major breakthrough. The use of virtual screening helped us to identify a cyclic hexapeptide AOA-2 that inhibits the adhesion of Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli to host cells and the formation of biofilm, thereby preventing the development of infection in vitro and in a murine sepsis peritoneal model. Inhibition of OmpA offers a strategy as monotherapy to address the urgent need for treatments for infections caused by Gram-negative bacilli.
Keyphrases
- gram negative
- multidrug resistant
- acinetobacter baumannii
- pseudomonas aeruginosa
- biofilm formation
- escherichia coli
- drug resistant
- induced apoptosis
- klebsiella pneumoniae
- staphylococcus aureus
- cystic fibrosis
- cell cycle arrest
- candida albicans
- intensive care unit
- endoplasmic reticulum stress
- signaling pathway
- oxidative stress
- antimicrobial resistance
- cell death
- acute kidney injury
- cell proliferation
- clinical trial