Combating virulence of Gram-negative bacilli by OmpA inhibition

• Published in: Scientific reports Vol. 7; no. 1; pp. 14683 - 11
• Main Authors: Vila-Farrés, Xavier, Parra-Millán, Raquel, Sánchez-Encinales, Viviana, Varese, Monica, Ayerbe-Algaba, Rafael, Bayó, Nuria, Guardiola, Salvador, Pachón-Ibáñez, María Eugenia, Kotev, Martin, García, Jesús, Teixidó, Meritxell, Vila, Jordi, Pachón, Jerónimo, Giralt, Ernest, Smani, Younes
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31-10-2017; Nature Publishing Group; Macmillan Publishers
• Subjects: 631/154/309/2144; 631/326/421; Acinetobacter baumannii - physiology; Acinetobacter Infections - drug therapy; Acinetobacter Infections - immunology; Adhesion; Alveolar Epithelial Cells - physiology; Animals; Anti-Bacterial Agents - therapeutic use; Bacilli; Bacterial Adhesion - drug effects; Bacterial Outer Membrane Proteins - antagonists & inhibitors; Biofilms; Cell Line; Desenvolupament de medicaments; Disease Models, Animal; Drug development; E coli; Escherichia coli - physiology; Escherichia coli Infections - drug therapy; Escherichia coli Infections - immunology; Female; Gram-negative bacilli; Humanities and Social Sciences; Humans; Membrane proteins; Mice; Mice, Inbred C57BL; Microorganismes patògens; multidisciplinary; Multidrug resistance; Pathogenic microorganisms; Pathogens; Peptides - genetics; Peptides - metabolism; Peptides - therapeutic use; Peritoneum; Pseudomonas aeruginosa - physiology; Pseudomonas Infections - drug therapy; Pseudomonas Infections - immunology; RNA Helicases - genetics; RNA Helicases - metabolism; RNA Helicases - therapeutic use; Science; Science (multidisciplinary); Sepsis; Sepsis - immunology; Virulence factors; Virulence Factors - antagonists & inhibitors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-14972-y

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.