RESUMO
Inhibition of apoptotic response of host cells during an early phase of infection is a strategy used by many enteroinvasive bacterial pathogens to enhance their survival. Here, we report the identification of a soluble form of the pilus protein FimA from the culture supernatants of E. coli K1, Salmonella, and Shigella that can potently inhibit Bax-mediated release of cytochrome c from isolated mitochondria. Similar to the infected cells, HCT116 cells stably expressing FimA display a delay in the integration of Bax into outer mitochondrial membrane induced by apoptotic stimuli. FimA targets to mitochondria through binding to VDAC1, which is a prerequisite step for E. coli K1 to render the short-term blockade of apoptotic death in the host cells. Interestingly, FimA strengthens the VDAC1-hexokinase interaction and prevents dissociation of hexokinase from VDAC1 triggered by apoptotic stimuli. Together, these data thus reveal a paradigm of antiapoptosis mechanism undertaken by the enteroinvasive bacteria.
Assuntos
Apoptose , Enterobacteriaceae/metabolismo , Proteínas de Fímbrias/metabolismo , Hexoquinase/metabolismo , Mitocôndrias/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Sequência de Aminoácidos , Citocromos c/metabolismo , Enterobacteriaceae/química , Enterobacteriaceae/genética , Escherichia coli/química , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Fímbrias/química , Células HCT116 , Hexoquinase/genética , Humanos , Dados de Sequência Molecular , Pili Sexual/química , Pili Sexual/metabolismo , Ligação Proteica , Salmonella enterica/metabolismo , Alinhamento de Sequência , Shigella flexneri/metabolismo , Transdução de Sinais , Solubilidade , Canal de Ânion 1 Dependente de Voltagem/genéticaRESUMO
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