Mónica A. Delgado, Ph.D.

Title
Researcher and Assistant Professor
Department
Department of Nutrition Biochemistry
Institution
National University of Tucuman
Address
Chacabuco 461
City
San Miguel de Tucuman
Country
Argentina
E-mail
monicad[at]fbqf.unt.edu.ar
Website
http://www.insibio.unt.edu.ar/investigacion.html
Research Field
Microbiology
Award Year
2003
Country Of Origin
Argentina
Mentor Name
Eduardo A. Groisman, Ph.D.

Research

Our laboratory focuses on the study of the signal transduction mechanism of RcsCDB system and in the signal that induces this activation, in S. Typhimurium. Moreover, we are searching for new RcsB-regulated genes that can help us to determine metabolic pathways affected by system activation. RcsCDB system is unusual in that it consists of three proteins, RcsC sensor that resembles a hybrid sensor domain of TCS that lacks of PTH domain; the RcsB response regulator, and the protein RcsD domain containing a pseudo-HK, the ATP binding and Hpt domains. Although many factors have been reported to induce Rcs system, the physiological signal that leads to this activation remains unknown. Our results showed that the system has a negative feedback mechanism caused by high levels of the regulator. This is because the rcsB gene is controlled by activity of two promoters. Furthermore, we demonstrated that constitutive activation of RcsC, rcsC11 mutant, dramatically attenuates virulence and a null rcsB mutant fully restored this phenotype, indicating that the attenuation is caused by an elevated expression of RcsB-regulated genes. Thus we have shown that many genes, involved in virulence, are controlled in a specific time and place by the RcsB regulator, thus concluding that the rcsC11 mutant is able to survive within the host without causing disease, and induce the host immunity to a second challenge with the virulent wild-type S. Typhimurium strain. These results place to the rcsC11 mutant as a good candidate for the vaccine development with live organisms attenuated in their virulence.

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