title: Hcp family proteins secreted via the type VI secretion system coordinately regulate Escherichia coli K1 interaction with human brain microvascular endothelial cells.
abstract: Type VI secretion systems (T6SSs) are involved in the pathogenicity of several gram-negative bacteria. Based on sequence analysis, we found that a cluster of Escherichia coli virulence factors (EVF) encoding a putative T6SS exists in the genome of the meningitis-causing E. coli K1 strain RS218. The T6SS-associated deletion mutants exhibited significant defects in binding to and invasion of human brain microvascular endothelial cells (HBMEC) compared with the parent strain. Hcp family proteins (the hallmark of T6SS), including Hcp1 and Hcp2, were localized in the bacterial outer membrane, but the involvements of Hcp1 and Hcp2 have been shown to differ in E. coli-HBMEC interaction. The deletion mutant of hcp2 showed defects in the bacterial binding to and invasion of HBMEC, while Hcp1 was secreted in a T6SS-dependent manner and induced actin cytoskeleton rearrangement, apoptosis, and the release of interleukin-6 (IL-6) and IL-8 in HBMEC. These findings demonstrate that the T6SS is functional in E. coli K1, and two Hcp family proteins participate in different steps of E. coli interaction with HBMEC in a coordinate manner, e.g., binding to and invasion of HBMEC, the cytokine and chemokine release followed by cytoskeleton rearrangement, and apoptosis in HBMEC. This is the first demonstration of the role of T6SS in meningitis-causing E. coli K1, and T6SS-associated Hcp family proteins are likely to contribute to the pathogenesis of E. coli meningitis.
authors.affiliation: Laboratory of Bacterial Pathogenesis, Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Jinjing
authors.initials: J
authors.lastname: Ni
authors.forename: Lingbing
authors.initials: L
authors.lastname: Zeng
authors.forename: Qihui
authors.initials: Q
authors.lastname: Teng
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhao
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Guo
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000942:Antigens, Bacterial; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000032:analysis; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000382:microbiology*; D004926:Escherichia coli / Q000145:classification / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D011135:Polysaccharides, Bacterial; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D029968:Escherichia coli Proteins; C571202:HCP-2 protein, E coli; C571201:HCP1 protein, E coli; D026901:Membrane Transport Proteins; D011135:Polysaccharides, Bacterial; D037521:Virulence Factors; C036962:capsular polysaccharide K1