Selective inhibition of the amyloid matrix of Escherichia coli biofilms by a bifunctional microbial metabolite

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dc.citation.titlenpj Biofilms and Microbiomes
dc.citation.volume1-7
dc.citation.volume9
dc.contributor.orcidhttps://orcid.org/0000-0002-6574-1702
dc.contributor.orcidhttps://orcid.org/0000-0002-8903-0673
dc.contributor.orcidhttps://orcid.org/0000-0001-5493-8537
dc.contributor.orcidhttps://orcid.org/0000-0002-3926-384X
dc.creatorCordisco, Estefanía
dc.creatorZanor, María Inés
dc.creatorMoreno, Diego M.
dc.creatorSerra, Diego Omar
dc.date.accessioned2024-02-19T14:11:41Z
dc.date.available2024-02-19T14:11:41Z
dc.date.issued2023-10-19
dc.description.abstractThe propensity of bacteria to grow collectively in communities known as biofilms and their ability to overcome clinical treatments in this condition has become a major medical problem, emphasizing the need for anti-biofilm strategies. Antagonistic microbial interactions have extensively served as searching platforms for antibiotics, but their potential as sources for anti-biofilm compounds has barely been exploited. By screening for microorganisms that in agar-set pairwise interactions could antagonize Escherichia coli’s ability to form macrocolony biofilms, we found that the soil bacterium Bacillus subtilis strongly inhibits the synthesis of amyloid fibers –known as curli-, which are the primary extracellular matrix (ECM) components of E. coli biofilms. We identified bacillaene, a B. subtilis hybrid non-ribosomal peptide/polyketide metabolite, previously described as a bacteriostatic antibiotic, as the effector molecule. We found that bacillaene combines both antibiotic and anti-curli functions in a concentration-dependent order that potentiates the ecological competitiveness of B. subtilis, highlighting bacillaene as a metabolite naturally optimized for microbial inhibition. Our studies revealed that bacillaene inhibits curli by directly impeding the assembly of the CsgB and CsgA curli subunits into amyloid fibers. Moreover, we found that curli inhibition occurs despite E. coli attempts to reinforce its protective ECM by inducing curli genes via a RpoS-mediated competition sensing response trigged by the threatening presence of B. subtilis. Overall, our findings illustrate the relevance of exploring microbial interactions not only for finding compounds with unknown and unique activities, but for uncovering additional functions of compounds previously categorized as antibiotics.
dc.description.filFil: Cordisco, Estefanía. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Estructura y Fisiología de Biofilms Microbianos. Consejo Nacional de Investigaciones Científicas y Técnicas (IBR-CONICET); Argentina.
dc.description.filFil: Zanor, María Inés. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Metabolismo y Señalización en Plantas. Consejo Nacional de Investigaciones Científicas y Técnicas (IBR-CONICET); Argentina.
dc.description.filFil: Moreno, Diego M. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET-UNR); Argentina.
dc.description.filFil: Serra, Diego Omar. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Estructura y Fisiología de Biofilms Microbianos. Consejo Nacional de Investigaciones Científicas y Técnicas (IBR-CONICET); Argentina.
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica
dc.description.sponsorshipAgencia Santafesina de Ciencia, Tecnología e Innovación (ASaCTeI): PEICID-2021-045, PICT-2020-SERIEA-00534
dc.description.sponsorshipAlexander von Humboldt-Stiftung (AvH): Ref 3.4 – 8151/20 005
dc.identifier.issn2055-5008
dc.identifier.urihttps://hdl.handle.net/2133/26700
dc.language.isoen
dc.publisherNature Research
dc.relation.publisherversionhttps://www.nature.com/articles/s41522-023-00449-6#rightslink
dc.relation.publisherversionhttps://doi.org/10.1038/s41522-023-00449-6
dc.rightsopenAccess
dc.rights.holderCordisco, Estefanía
dc.rights.holderZanor, María Inés
dc.rights.holderMoreno, Diego M.
dc.rights.holderSerra, Diego Omar
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textCC BY 4.0 DEED Attribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAmyloid
dc.subjectAmyloidogenic proteins
dc.subjectAnti-bacterial agents
dc.subjectBacteria
dc.subjectBiofilms
dc.subjectEscherichia coli
dc.subjectPolyenes
dc.titleSelective inhibition of the amyloid matrix of Escherichia coli biofilms by a bifunctional microbial metabolite
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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