The Multivalent Adhesion Molecule SSO1327 plays a key role in Shigella sonnei pathogenesis.
Shigella sonnei is a bacterial pathogen and causative agent of bacillary dysentery. It deploys a type III secretion system to inject effector proteins into host epithelial cells and macrophages, an essential step for tissue invasion and immune evasion. Although the arsenal of bacterial effectors and their cellular targets have been studied extensively, little is known about the prerequisites for deployment of type III secreted proteins during infection. Here, we describe a novel S. sonnei adhesin, SSO1327 which is a multivalent adhesion molecule (MAM) required for invasion of epithelial cells and macrophages and for infection in vivo. The S. sonnei MAM mediates intimate attachment to host cells, which is required for efficient translocation of type III effectors into host cells. SSO1327 is non-redundant to IcsA; its activity is independent of type III secretion. In contrast to the up-regulation of IcsA-dependent and independent attachment and invasion by deoxycholate in Shigella flexneri, deoxycholate negatively regulates IcsA and MAM in S. sonnei resulting in reduction in attachment and invasion and virulence attenuation in vivo. A strain deficient for SSO1327 is avirulent in vivo, but still elicits a host immune response.
Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, Glasgow, UK.|Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
Rasha Y
RY
Mahmoud
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Daniel Henry
DH
Stones
Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, Glasgow, UK.
Wenqin
W
Li
Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
Mohamed
M
Emara
Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
Ramadan A
RA
El-Domany
The center of Translational Medicine, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, China.
Depu
D
Wang
Institute for Cancer Research, School of Basic Medical Science, Health Science Center, Xi'an Jiao Tong University, Xi'an, China.
Yili
Y
Wang
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Anne Marie
AM
Krachler
Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, Glasgow, UK.
Jun
J
Yu
D018829:Adhesins, Bacterial / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D003840:Deoxycholic Acid / Q000378:metabolism; D004195:Disease Models, Animal; D004405:Dysentery, Bacillary / Q000382:microbiology* / Q000503:physiopathology; D004847:Epithelial Cells / Q000382:microbiology; D006168:Guinea Pigs; D006367:HeLa Cells; D006801:Humans; D007637:Keratoconjunctivitis / Q000382:microbiology; D007814:Larva / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D009036:Moths; D012763:Shigella flexneri / Q000378:metabolism; D012764:Shigella sonnei / Q000235:genetics* / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics; D000069296:Type III Secretion Systems / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014774:Virulence
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000069296:Type III Secretion Systems; C058483:virG protein, Shigella flexneri; D003840:Deoxycholic Acid