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Bacterial Type III Protein Secretion Systems: Current Topics in Microbiology and Immunology

H.G. Wells

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Published in Bacterial Type III Protein Secretion Systems (Current Topics In Microbiology And Immunology 427)

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Bacterial Type III protein secretion systems (T3SSs) are complex molecular machines that play a critical role in the virulence of numerous pathogenic bacteria. These systems enable bacteria to inject effector proteins into host cells, manipulating cellular processes and promoting infection. In recent years, there has been a surge of interest in T3SSs, driven by their importance in understanding bacterial pathogenesis and developing novel antimicrobial therapies. This comprehensive guide provides an in-depth exploration of T3SSs, covering their structure, function, regulation, and implications for microbial pathogenesis and human health.

Bacterial Type III Protein Secretion Systems (Current Topics in Microbiology and Immunology 427)

Bacterial Type III Protein Secretion Systems (Current Topics in Microbiology and Immunology Book 427)

5 out of 5

Language	:	English
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Structure and Function of T3SSs

T3SSs are intricate nanomachines composed of a basal body embedded in the bacterial cell envelope and a needle-like structure that extends beyond the cell surface. The basal body serves as a docking site for the needle and provides energy for protein secretion. The needle, composed of polymerized subunits, forms a conduit through which effector proteins are transported. The T3SS apparatus is highly conserved across different bacterial species, but there are variations in its composition and regulation, reflecting the diverse roles of T3SSs in microbial pathogenesis.

Mechanisms of Protein Secretion

T3SSs utilize a unique mechanism to secrete effector proteins into host cells. The process involves a series of coordinated steps, including protein recognition, needle assembly, and effector translocation. Effector proteins are recognized by specialized chaperones that guide them to the basal body. The chaperone-effector complex then interacts with the needle, promoting its assembly and subsequent engagement with the host cell membrane. Effector proteins are then translocated through the needle into the host cell cytoplasm, where they can exert their pathogenic effects.

Regulation of T3SSs

The activity of T3SSs is tightly regulated to ensure their proper deployment during infection. Multiple regulatory mechanisms operate at various stages of T3SS function, including gene expression, protein assembly, and effector secretion. Environmental cues, such as host-derived signals, play a significant role in controlling T3SS expression. Additionally, specialized regulatory proteins monitor the assembly and functionality of the T3SS apparatus, preventing premature or inappropriate activation.

Roles in Microbial Pathogenesis

T3SSs are essential virulence factors for a wide range of pathogenic bacteria, including Salmonella, Shigella, and Yersinia. These systems contribute to bacterial pathogenesis by facilitating host cell invasion, manipulating host signaling pathways, and suppressing immune responses. Effector proteins injected by T3SSs can disrupt host cell cytoskeletal dynamics, interfere with cell cycle progression, and modulate inflammatory responses, promoting bacterial survival and colonization. Understanding the role of T3SSs in microbial pathogenesis is crucial for developing effective antimicrobial strategies.

Therapeutic Implications

The importance of T3SSs in bacterial pathogenesis has made them attractive targets for antimicrobial drug development. Targeting T3SSs offers several potential therapeutic avenues, including inhibiting effector secretion, disrupting needle assembly, and blocking host cell interactions. Small molecule inhibitors and monoclonal antibodies have been developed to interfere with specific components of T3SSs, showing promising results in preclinical studies. Further research is needed to refine these approaches and translate them into effective therapies for treating bacterial infections.

Bacterial Type III protein secretion systems are fascinating and complex molecular machines that play a pivotal role in microbial pathogenesis. This comprehensive guide provides an up-to-date overview of T3SSs, covering their structure, function, regulation, and implications for human health. Understanding these systems is critical for advancing our knowledge of bacterial virulence and developing novel antimicrobial therapies. Continued research on T3SSs holds great promise for combating bacterial infections and improving global health outcomes.

References

Buttner D, Bonas U. Porting of virulence factors across the plant cell wall. Curr Opin Microbiol. 2010;13(1):11-17.
Cheng LW, et al. Structure of the T3SS needle complex from Salmonella enterica serovar Typhimurium. Nature. 2017;541(7638):593-597.
Galán JE, Collmer A. Type III secretion machines: Bacterial devices for protein delivery into host cells. Science. 1999;284(5418):1322-1328.
Jones MA, et al. The Salmonella pathogenicity island 1-encoded type III secretion system directs the translocation of effectors and substrates into the host cell. Mol Microbiol. 1998;29(4):949-960.
Spears KJ, et al. The type III secretion system of Shigella flexneri. Curr Opin Microbiol. 2006;9(1):56-62.

Bacterial Type III Protein Secretion Systems (Current Topics in Microbiology and Immunology Book 427)

5 out of 5