Antibacterial activity of alkyl gallates is a combination of direct targeting of FtsZ and permeabilization of bacterial membranes

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dc.contributor.authorKról, Ewa
dc.contributor.authorBorges, Anabela de Sousa
dc.contributor.authorSilva, Isabel da [UNESP]
dc.contributor.authorPolaquini, Carlos R. [UNESP]
dc.contributor.authorRegasini, Luis O. [UNESP]
dc.contributor.authorFerreira, Henrique [UNESP]
dc.contributor.authorScheffers, Dirk-Jan
dc.contributor.institutionUniversity of Groningen
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2015-10-21T13:14:52Z
dc.date.available2015-10-21T13:14:52Z
dc.date.issued2015-04-29
dc.description.abstractAlkyl gallates are compounds with reported antibacterial activity. One of the modes of action is binding of the alkyl gallates to the bacterial membrane and interference with membrane integrity. However, alkyl gallates also cause cell elongation and disruption of cell division in the important plant pathogen Xanthomonas citri subsp. citri, suggesting that cell division proteins may be targeted by alkyl gallates. Here, we use Bacillus subtilis and purified B. subtilis FtsZ to demonstrate that FtsZ is a direct target of alkyl gallates. Alkyl gallates disrupt the FtsZ-ring in vivo, and cause cell elongation. In vitro, alkyl gallates bind with high affinity to FtsZ, causing it to cluster and lose its capacity to polymerize. The activities of a homologous series of alkyl gallates with alkyl side chain lengths ranging from five to eight carbons (C5-C8) were compared and heptyl gallate was found to be the most potent FtsZ inhibitor. Next to the direct effect on FtsZ, alkyl gallates also target B. subtilis membrane integrity-however the observed anti-FtsZ activity is not a secondary effect of the disruption of membrane integrity. We propose that both modes of action, membrane disruption and anti-FtsZ activity, contribute to the antibacterial activity of the alkyl gallates. We propose that heptyl gallate is a promising hit for the further development of antibacterials that specifically target FtsZ.en
dc.description.affiliationDepartment of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands
dc.description.affiliationUnespDepartamento de Química e Ciências Ambientais, Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, Brazil
dc.description.affiliationUnespDepartamento de Bioquímica e Microbiologia, Instituto de Biociências, Universidade Estadual Paulista, Rio Claro, Brazil
dc.description.sponsorshipNetherlands Organisation for Scientific research (NWO)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipNWO Vidi grant
dc.description.sponsorshipPOPH/FSE and FCT (Fundacao para a Ciência e Tecnologia) from Portugal
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 2013/50367-8
dc.description.sponsorshipIdPOPH/FSE and FCT: SFRH/BD/78061/2011
dc.description.sponsorshipIdCNPq: 201196/2012-3
dc.format.extent1-12
dc.identifierhttp://journal.frontiersin.org/article/10.3389/fmicb.2015.00390/abstract
dc.identifier.citationFrontiers In Microbiology. Lausanne: Frontiers Research Foundation, v. 6, p. 1-12, 2015.
dc.identifier.doi10.3389/fmicb.2015.00390
dc.identifier.fileWOS000354966900001.pdf
dc.identifier.issn1664-302X
dc.identifier.urihttp://hdl.handle.net/11449/128875
dc.identifier.wosWOS:000354966900001
dc.language.isoeng
dc.publisherFrontiers Research Foundation
dc.relation.ispartofFrontiers In Microbiology
dc.relation.ispartofjcr4.019
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectAntibioticsen
dc.subjectNatural productsen
dc.subjectCell divisionen
dc.subjectCitrus cankeren
dc.subjectXanthomonas citrien
dc.subjectBacillus subtilisen
dc.titleAntibacterial activity of alkyl gallates is a combination of direct targeting of FtsZ and permeabilization of bacterial membranesen
dc.typeArtigo
dcterms.rightsHolderFrontiers Research Foundation
unesp.author.orcid0000-0002-9439-9168[7]
unesp.author.orcid0000-0001-5913-0246[4]
unesp.author.orcid0000-0001-9617-9858[3]
unesp.author.orcid0000-0002-9183-9420[6]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Rio Claropt
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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Artigos - Química e Ciências Ambientais - IBILCE
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