The Inside Story of Shigella Invasion of Intestinal Epithelial Cells

Carayol, Nathalie; Nhieu, Guy Tran Van

doi:10.1101/cshperspect.a016717

Cited by 60 publications

(65 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Shigella spp. rely on a T3SS to promote uptake by the epithelial cells lining the large intestine of their human hosts, initiate apoptosis of resident macrophages, escape endocytic vacuoles, and provide actin‐based motility . Providing these critical roles at the correct point during infection requires that the T3SS is under strict control at many levels including transcriptional and translational regulation as well as control over the maturation and activation of the injectosome itself .…”

Section: Discussionmentioning

confidence: 99%

Spa47 is an oligomerization‐activated type three secretion system (T3SS) ATPase from Shigella flexneri

et al. 2016

View full text Add to dashboard Cite

Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents.

show abstract

Section: Discussionmentioning

confidence: 99%

Spa47 is an oligomerization‐activated type three secretion system (T3SS) ATPase from Shigella flexneri

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Shigellosis or bacillary dysentery is typically characterized by bacterial invasion and multiplication within intestinal epithelial cells (680). Shigella invades cells through a type III secretion apparatus, in which contact with the host cell initiates bacterial secretion of Ipa and other proteins (681).…”

Section: Shigellamentioning

confidence: 99%

Blood Groups in Infection and Host Susceptibility

2015

View full text Add to dashboard Cite

SUMMARY Blood group antigens represent polymorphic traits inherited among individuals and populations. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Several blood groups can modify the innate immune response to infection. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome.

show abstract

“…Shigella species are closely related to E. coli and cause invasive, localized diarrheal disease. Infection by Shigella involves entry of the bacterium into host M cells of the colon and rectum, destruction of the phagosomal membrane and release into the cytoplasm, intracellular motility via the host actin system, and lysis of host cells and infection of neighboring cells during repeated cycles of reinfection (327). Pathogenicity is dependent upon the presence of a 220-kb virulence plasmid and the T3SS that it encodes (328).…”

mentioning

confidence: 99%

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Vakulskas

Potts

Babitzke

et al. 2015

Microbiol Mol Biol Rev

302

400

View full text Add to dashboard Cite

SUMMARY Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5′ untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens.

show abstract

The Inside Story of Shigella Invasion of Intestinal Epithelial Cells

Cited by 60 publications

References 85 publications

Spa47 is an oligomerization‐activated type three secretion system (T3SS) ATPase from Shigella flexneri

Spa47 is an oligomerization‐activated type three secretion system (T3SS) ATPase from Shigella flexneri

Blood Groups in Infection and Host Susceptibility

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Contact Info

Product

Resources

About