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dc.contributor.author
Fernández Brando, Romina Jimena
dc.contributor.author
Yamaguchi, Nao
dc.contributor.author
Tahoun, Amin
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McAteer, Sean P.
dc.contributor.author
Gillespie, Trudi
dc.contributor.author
Wang, Dai
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Argyle, Sally A.
dc.contributor.author
Palermo, Marina Sandra
dc.contributor.author
Gally, David L.
dc.date.available
2018-04-19T20:00:33Z
dc.date.issued
2015-12
dc.identifier.citation
Fernández Brando, Romina Jimena; Yamaguchi, Nao; Tahoun, Amin; McAteer, Sean P.; Gillespie, Trudi; et al.; Type III secretion-dependent sensitivity of Escherichia coli O157 to specific ketolides; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 60; 1; 12-2015; 459-470
dc.identifier.issn
0066-4804
dc.identifier.uri
http://hdl.handle.net/11336/42742
dc.description.abstract
A subset of Gram negative bacterial pathogens use a type 3 secretion system (T3SS) to open up a conduit into eukaryotic cells in order to inject effector proteins. These modulate pathways to enhance bacterial colonization. In this study we screened established bioactive compounds for any that could repress T3SS expression in enterohemorrhagic Escherichia coli (EHEC) O157. The ketolides, telithromycin and subsequently solithromycin both demonstrated repressive effects on expression of the bacterial T3SS at sub-minimum inhibitory (sub-MIC) concentrations, leading to significant reductions in bacterial binding and actin-rich pedestal formation on epithelial cells. Pre-incubation of epithelial cells with solithromycin resulted in significantly less attachment of E. coli O157. Moreover, bacteria expressing the T3SS were more susceptible to solithromycin and there was significant preferential killing of E. coli O157 when added to epithelial cells pre-exposed to the ketolide. This killing was dependent on expression of the T3SS. Taken together, this research indicates that the ketolide may traffic back into the bacteria via the T3SS from accumulated levels in epithelial cells. Considering that neither ketolide induces the SOS response, non-toxic members of this class of antibiotic, such as solithromycin, should be considered for future testing and trials in relation to EHEC infections. These antibiotics may also have broader significance for treating other pathogenic bacteria, including intracellular bacteria, that express a T3SS.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society for Microbiology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Escherichia Coli,
dc.subject
Ketolide
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Sos Response,
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Shiga Toxin
dc.subject.classification
Inmunología
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Type III secretion-dependent sensitivity of Escherichia coli O157 to specific ketolides
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-04-09T19:05:15Z
dc.journal.volume
60
dc.journal.number
1
dc.journal.pagination
459-470
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Fernández Brando, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Yamaguchi, Nao. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Tahoun, Amin. University of Edinburgh; Reino Unido. Kafrelsheikh University; Egipto
dc.description.fil
Fil: McAteer, Sean P.. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Gillespie, Trudi. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Wang, Dai. University of Edinburgh; Reino Unido. Xiamen University; China
dc.description.fil
Fil: Argyle, Sally A.. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Gally, David L.. University of Edinburgh; Reino Unido
dc.journal.title
Antimicrobial Agents and Chemotherapy
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/60/1/459.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/AAC.02085-15
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704242/
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