A Soluble Form of the Pilus Protein FimA Targets the VDAC-Hexokinase Complex at Mitochondria to Suppress Host Cell Apoptosis

• Published in: Molecular cell Vol. 37; no. 6; pp. 768 - 783
• Main Authors: Sukumaran, Sunil K., Fu, Nai Yang, Tin, Chua Boon, Wan, Kah Fei, Lee, San San, Yu, Victor C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2010
• Subjects: Amino Acid Sequence; Apoptosis; CELLCYCLE; Cytochromes c - metabolism; Cytochromes c - secretion; Enterobacteriaceae - chemistry; Enterobacteriaceae - genetics; Enterobacteriaceae - metabolism; Escherichia coli; Escherichia coli - chemistry; Escherichia coli - genetics; Escherichia coli - metabolism; Fimbriae Proteins - chemistry; Fimbriae Proteins - metabolism; HCT116 Cells; Hexokinase - genetics; Hexokinase - metabolism; Humans; HUMDISEASE; Mitochondria - metabolism; Mitochondria - secretion; Molecular Sequence Data; Pili, Sex - chemistry; Pili, Sex - metabolism; Protein Binding; PROTEINS; Salmonella; Salmonella enterica - metabolism; Sequence Alignment; Shigella; Shigella flexneri - metabolism; Signal Transduction; Solubility; Voltage-Dependent Anion Channel 1 - genetics; Voltage-Dependent Anion Channel 1 - metabolism; PROTEINS; CELLCYCLE; HUMDISEASE
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2010.02.015

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. ► Enteroinvasive bacteria block Bax integration and cytochrome c release in host cells ► A soluble form of the pilus protein FimA is a potent suppressor of cytochrome c release ► FimA targets to mitochondria through binding to VDAC1 ► FimA stabilizes VDAC1-hexokinase complex to inhibit apoptosis of host cells