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Combating virulence of Gram-negative bacilli by OmpA inhibition.

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dc.contributor.authorVila-Farres, Xavier
dc.contributor.authorParra-Millan, Raquel
dc.contributor.authorSanchez-Encinales, Viviana
dc.contributor.authorVarese, Monica
dc.contributor.authorAyerbe-Algaba, Rafael
dc.contributor.authorBayo, Nuria
dc.contributor.authorGuardiola, Salvador
dc.contributor.authorPachon-Ibañez, María Eugenia
dc.contributor.authorKotev, Martin
dc.contributor.authorGarcia, Jesus
dc.contributor.authorTeixido, Meritxell
dc.contributor.authorVila, Jordi
dc.contributor.authorPachon, Jeronimo
dc.contributor.authorGiralt, Ernest
dc.contributor.authorSmani, Younes
dc.contributor.funderConsejería de Salud y Bienestar of Andalusia
dc.contributor.funderConsejería de Economia, Innovación, Ciencia y Empleo of Andalusia
dc.contributor.funderMinisterio de Economía y Competitividad of Spain
dc.date.accessioned2023-01-25T10:01:12Z
dc.date.available2023-01-25T10:01:12Z
dc.date.issued2017-10-31
dc.description.abstractPreventing 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.
dc.description.sponsorshipWe thank V. López Casado, A. Gardel, C. Tomi, and C. Garcia for technical help, and J. Sánchez Céspedes for critical review of this manuscript. We also acknowledge the NMR facility of the University of Barcelona (CCiT UB). This study was supported by the Consejería de Salud y Bienestar (grant PI12–0069), the Consejería de Economia, Innovación, Ciencia y Empleo (grants CTS-6173/12, and 2014LLAV-00064) of Andalusia, Spain, and by Plan Nacional de I + D + i 2008–2011 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015/0001) co-financed by European Development Regional Fund “A way to achieve Europe”. This work led to the provisional patent application ES P201431400. Y. Smani is supported by the Subprograma Miguel Servet Tipo I from the Ministerio de Economía y Competitividad of Spain [CP15/01358]. IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain).
dc.description.versionSi
dc.identifier.citationVila-Farrés X, Parra-Millán R, Sánchez-Encinales V, Varese M, Ayerbe-Algaba R, Bayó N, et al. Combating virulence of Gram-negative bacilli by OmpA inhibition. Sci Rep. 2017 Oct 31;7(1):1-11.
dc.identifier.doi10.1038/s41598-017-14972-y
dc.identifier.essn2045-2322
dc.identifier.pmcPMC5666006
dc.identifier.pmid29089624
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666006/pdf
dc.identifier.unpaywallURLhttps://www.nature.com/articles/s41598-017-14972-y.pdf
dc.identifier.urihttp://hdl.handle.net/10668/11756
dc.issue.number1
dc.journal.titleScientific reports
dc.journal.titleabbreviationSci Rep
dc.language.isoen
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number11
dc.provenanceRealizada la curación de contenido 03/04/2025
dc.publisherNature Publishing Group
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDPI12–0069
dc.relation.projectIDCTS-6173/12
dc.relation.projectID2014LLAV-00064
dc.relation.projectIDCP15/01358
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-017-14972-y
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectDrug discovery and development
dc.subjectPathogens
dc.subject.decsCélulas
dc.subject.decsInfecciones
dc.subject.decsBiopelículas
dc.subject.decsAcinetobacter baumannii
dc.subject.decsBacterias
dc.subject.decsSepsis
dc.subject.decsTerapéutica
dc.subject.decsTécnicas In Vitro
dc.subject.decsTamizaje masivo
dc.subject.decsEscherichia coli
dc.subject.decsPseudomonas aeruginosa
dc.subject.meshAcinetobacter Infections
dc.subject.meshAcinetobacter baumannii
dc.subject.meshAlveolar Epithelial Cells
dc.subject.meshAnimals
dc.subject.meshAnti-Bacterial Agents
dc.subject.meshBacterial Adhesion
dc.subject.meshBacterial Outer Membrane Proteins
dc.subject.meshBiofilms
dc.subject.meshCell Line
dc.subject.meshDNA Helicases
dc.subject.meshDisease Models, Animal
dc.subject.meshEscherichia coli
dc.subject.meshEscherichia coli Infections
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMultifunctional Enzymes
dc.subject.meshPeptides
dc.subject.meshPseudomonas Infections
dc.subject.meshPseudomonas aeruginosa
dc.subject.meshRNA Helicases
dc.subject.meshSepsis
dc.subject.meshVirulence Factors
dc.titleCombating virulence of Gram-negative bacilli by OmpA inhibition.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number7
dspace.entity.typePublication

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