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Molecular and cell biology aspects of plague
1Microbial Pathogenesis Unit, Christian de Duve Institute of Cellular Pathology, and Faculté de Médecine, Université Catholique de Louvain, Avenue Hippocrate, 74, UCL 74.49, B-1200 Brussels, Belgium. cornelis@mipa.ucl.ac.be
Abstract:
A 70-kb virulence plasmid (sometimes called pYV) enables Yersinia spp. to survive and multiply in the lymphoid tissues of their host. It encodes the Yop virulon, a system consisting of secreted proteins called Yops and their dedicated type III secretion apparatus called Ysc. The Ysc apparatus forms a channel composed of 29 proteins. Of these, 10 have counterparts in almost every type III system. Secretion of some Yops requires the assistance, in the bacterial cytosol, of small individual chaperones called the Syc proteins. These chaperones act as bodyguards or secretion pilots for their partner Yop. Yop proteins fall into two categories. Some are intracellular effectors, whereas the others are "translocators" needed to deliver the effectors across the eukaryotic plasma membrane, into eukaryotic cells. The translocators (YopB, YopD, LcrV) form a pore of 16-23 A in the eukaryotic cell plasma membrane. The effector Yops are YopE, YopH, YpkA/YopO, YopP/YopJ, YopM, and YopT. YopH is a powerful phosphotyrosine phosphatase playing an antiphagocytic role by dephosphorylating several focal adhesion proteins. YopE and YopT contribute to antiphagocytic effects by inactivating GTPases controlling cytoskeleton dynamics. YopP/YopJ plays an anti-inflammatory role by preventing the activation of the transcription factor NF-kappaB. It also induces rapid apoptosis of macrophages. Less is known about the role of the phosphoserine kinase YopO/YpkA and YopM.
Insights
The Yersinia virulence plasmid (pYV) uses the Ysc secretion system to deliver Yop proteins into host cells. These Yops, aided by Syc chaperones, disrupt host functions to promote bacterial survival.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- The 70-kb virulence plasmid (pYV) in Yersinia spp. is crucial for host survival and multiplication in lymphoid tissues.
- This plasmid encodes the Yop virulon, a type III secretion system (T3SS) comprising Yop proteins and the Ysc secretion apparatus.
Purpose of the Study:
- To elucidate the mechanisms by which Yersinia spp. utilize the Yop virulon and Ysc apparatus for pathogenesis.
- To categorize and describe the functions of various Yop effector proteins and their roles in host manipulation.
Main Methods:
- The study focuses on the molecular components of the Ysc apparatus and the Yop proteins.
- Analysis of Yop protein functions, including effector and translocator roles, and their interactions with host cells.
Main Results:
- The Ysc apparatus, composed of 29 proteins, facilitates the secretion of Yops, with 10 components conserved across most T3SS.
- Syc proteins act as chaperones, assisting in the secretion of specific Yops.
- Yop proteins function as intracellular effectors or translocators; translocators (YopB, YopD, LcrV) form a pore in the host cell membrane, while effectors (YopE, YopH, YpkA/YopO, YopP/YopJ, YopM, YopT) manipulate host processes.
Conclusions:
- YopH dephosphorylates focal adhesion proteins, contributing to antiphagocytosis.
- YopE and YopT inactivate GTPases, disrupting the cytoskeleton and aiding immune evasion.
- YopP/YopJ inhibits NF-kappaB activation and induces macrophage apoptosis, suppressing inflammation and innate immunity.