identification-host-pathways-targeted-bacterial-effector-proteins

Identification of Host Pathways Targeted by Bacterial Effector Proteins using Yeast Toxicity and Suppressor Screens

Intracellular bacteria secrete virulence factors called effector proteins into the host cytosol that act to subvert host proteins and/or their associated ...

University of Iowa

Intracellular bacteria have developed numerous strategies to hijack host vesicular trafficking pathways to form their unique replicative niches. To promote intracellular replication, the bacteria must interact with host organelles and modulate host signaling pathways to acquire nutrients and membrane for the growing parasitophorous vacuole all while suppressing activation of the immune response. To facilitate host cell subversion, bacterial pathogens use specialized secretion systems to deliver bacterial virulence factors, termed effectors, into the host cell that mimic, agonize, and/or antagonize the function of host proteins. In this review we will discuss how bacterial effector proteins from  serovar Typhimurium, , and  manipulate the endocytic and secretory pathways. Understanding how bacterial effector proteins manipulate host processes not only gives us keen insight into bacterial pathogenesis, but also enhances our understanding of how eukaryotic membrane trafficking is regulated.

Subversion of the Endocytic and Secretory Pathways by Bacterial Effector Proteins.

Chlamydial infection requires the formation of a membrane-bound vacuole, termed the inclusion, that undergoes extensive interactions with select host organelles. The importance of the Inc protein CT229 in the formation and maintenance of the chlamydial inclusion was recently highlighted by studies demonstrating that its absence during infection results in reduced bacterial replication, premature inclusion lysis, and host cell death. Previous reports have indicated that CT229 binds Rab GTPases; however, the physiological implications of this interaction are unknown. Here, we show that CT229 regulates host multivesicular trafficking by recruiting multiple Rab GTPases and their cognate effectors to the inclusion. We demonstrate that CT229 specifically modulates clathrin-coated vesicle trafficking and regulates the trafficking of transferrin and the mannose-6-phosphate receptor, both of which are crucial for proper chlamydial development. This study highlights CT229 as a master regulator of multiple host vesicular trafficking pathways essential for chlamydial infection.

Chlamydia trachomatis CT229 Subverts Rab GTPase-Dependent CCV Trafficking Pathways to Promote Chlamydial Infection.

Chlamydia trachomatis is an important human pathogen that prior to 2011 was largely intractable to genetic manipulation. Here we describe the application of a group II intron, referred to as TargeTron, for site-specific insertional inactivation of target genetic loci in the obligate, intracellular bacteria C. trachomatis. In this chapter, we outline the methods for intron retargeting, chlamydia transformation, and mutant verification. We also outline a method for complementation of TargeTron mutants. Furthermore, we discuss potential pitfalls and alternative strategies for generating mutants with TargeTron technology.

Article	Year
Subversion of the Endocytic and Secretory Pathways by Bacterial Effector Proteins. Frontiers in cell and developmental biology\| PubMed ID: 29417046	2018
Chlamydia trachomatis CT229 Subverts Rab GTPase-Dependent CCV Trafficking Pathways to Promote Chlamydial Infection. Cell reports\| PubMed ID: 30893609	2019
Mutagenesis of Chlamydia trachomatis Using TargeTron. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 31385276	2019

Mary M. Weber

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