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Analysis of the molecular and cellular function of SteA, a Salmonella virulence protein

Instituto de Tecnologia Química e Biológica
Project classification

Scientific area

1.6 Biological sciences (Medical sciences go to scientific area 3.n; Agricultural sciences go to scientific area 4.n)

Discipline(s)

Other biological topics

Project description

Project title

Analysis of the molecular and cellular function of SteA, a Salmonella virulence protein

Scientific Coordinator's name:

Jaime Mota

Scientific Coordinator's e-mail:

jmota@itqb.unl.pt

Principal R&D Unit:

Instituto de Tecnologia Química e Biológica

Other R&D Units involved in the project:

Universidad Complutense de Madrid

Project keyword(s)

Salmonella Type III secretion Effectors Membrane traffic

Short abstract and comments

Salmonella enterica serovars are facultative intracellular bacteria causing typhoid fever and gastrointestinal diseases. These infections remain important causes of human morbidity and mortality. S. enterica serovar Typhimurium (S. Typhimurium) has been extensively used to study Salmonella biology and virulence, due to the availability of sophisticated genetic tools and of excellent tissue culture and animal models of infection. S. enterica encodes two distinct type III secretion systems (T3SSs) within its pathogenicity islands 1 and 2 (SPI1 and SPI2). T3SSs are multi-protein complex machines used by many Gram-negative bacteria to inject virulence proteins (effectors) into eukaryotic host cells. The effectors modulate a wide range of cellular pathways to promote bacterial proliferation. The SPI1-encoded T3SS (T3SS1) is activated extracellularly and translocates >15 effectors across the host cell plasma membrane. The SPI2-encoded T3SS (T3SS2) is activated within host cells and translocates >25 effectors across the membrane-bound compartment in which intracellular bacteria reside and replicate, the Salmonella-containing vacuole (SCV). In general, T3SS1 effectors promote invasion of gut epithelial cells and initiate intestinal inflammation. They modulate host cell actin dynamics and signaling pathways. A major virulence function of T3SS2 is to mediate bacterial intravacuolar replication. This is probably achieved through the action of T3SS2 effectors on host vesicular traffic. There is also overlap between the functions of T3SS1 and T3SS2: at least 9 effectors are secreted by both systems, T3SS1 effectors participate in SCV maturation, and T3SS2 plays a role in intestinal inflammation. Although the function of various Salmonella effectors has been studied in considerable detail, there are several others of which our knowledge is poor. SteA belongs to the group of the latter. Still, different studies indicate that SteA plays an important role in Salmonella virulence. First, a S. Typhimurium steA deletion mutant (?steA) displays virulence defects in mice infection models. Second, SteA is translocated into host cells during in vivo infection of mice. In this project, we will perform a thorough characterization of the role of SteA. To do this, our specific objectives are: • To characterize the interaction between SteA and its host cell target(s) • To characterize the phenotype(s) associated to S. Typhimurium ?steA during infection of tissue culture cells; • To characterize the effects of SteA ectopic expression both in mammalian cells and in the yeast Saccharomyces cerevisiae as a eukaryotic model system; • To characterize the regions and residues of SteA required for its function(s).

Potential uses/indications

This project has the fundamental importance of furthering our knowledge about the molecular and cellular mechanisms underlying bacterial pathogenesis. It could also lead to new ideas to develop vaccines or drug targets against bacterial infections and to novel insights into eukaryotic host cell processes.

Status

Ongoing

Partner Status: Seeking Partners?

No

Project weblink

http://n/a

Grant number (QREN, FP7, Eureka, etc)

PTDC/BIA-MIC/116780/2010

Last edited on

2012-12-05 17:05:15

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