Combating virulence of Gram-negative bacilli by OmpA inhibition

通过抑制OmpA来抵抗革兰氏阴性杆菌的毒性

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作者:Xavier Vila-Farrés, Raquel Parra-Millán, Viviana Sánchez-Encinales, Monica Varese, Rafael Ayerbe-Algaba, Nuria Bayó, Salvador Guardiola, María Eugenia Pachón-Ibáñez, Martin Kotev, Jesús García, Meritxell Teixidó, Jordi Vila, Jerónimo Pachón, Ernest Giralt, Younes Smani

Abstract

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.

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