1. Study of the RcsB-dependent genes regulation involved in the Salmonella virulence.
The activation of the RcsCDB system is required to modulate a wide variety of genes involved in physiological processes such as motility, cell division, osmoregulation, and Salmonella virulence, among others.
This system activation is widely conserved, mainly in Salmonella enterica serovar Typhi, the agent of typhoid fever in humans, and in Salmonella enterica serovar Typhimurium, causative agent of gastroenteritis and systemic infections in humans and other animals.
2. Structural and functional study of the Salmonella Typhimurium RcsCDB system’s components.
The results of our group determined that the RcsCDB regulatory system has at least three activation pathways, indicating that there is more than one signal that produces it.
The aim of this project is to establish the mechanism and signaling conditions that lead to the system activation to control the gene expression during different stages and conditions of the bacterial growth.
In addition, we pretend to establish the structure of the system's Histidin-Kinase sensors in conditions of activation and non-activation, which will help us recognize the putative ligands that bind to the sensor and lead the signal transduction of this system. Thus we could to determine the molecule/s that is/are capable of activating it.
3. Vaccines development able to control the incidence of the main bacterial infections in the NWA population.
In our group we study the S. Typhimurium rcsC11 mutant, which produce the RcsCDB system's constitutive activation, and consequently producing a strong attenuation of this pathogen's virulence. In addition, we observed that this mutant triggers a strong immune response, protecting the host from the virulent strain’s attack.
To complete this project, an epidemiological study was carried out to isolate and characterize the main bacterial agents of these gastroenteric diseases, being Shigella fexneri 2 the pathogen with the highest incidence. Currently, our group has a large number of these pathogens, which were isolated from different hospitals of the NWA region.
Based on the results obtained, we direct this line of work to the development of attenuated and vectors vaccines expressing antigenic proteins isolated from recurrent pathogens in the NWA population, such as Salmonella Typhimuriu and Shigella fexneri 2, respectively, to promote the use of appropriate vaccines to those incident serovars, and as a preventive action that helps reduce health inequalities and promote technical excellence in vaccination services.
4- Study of mobile genetic elements (integrons, bacteriophages and CRISPR) on the evolutionary dynamics of the incident multidrug-resistant -pathogens (MDR): biocontrol and eradication methods.
The subject of this work complements the study and development of attenuated and vectors vaccines, as part of the Argentina Innovative Plan 2020 (National Plan of Science, Technology and Productive Innovation)
Our goal is the detection and characterization of antibiotic resistance cassettes and virulence genes (located in integrons) present in clinical isolates of Shigella sp. obtained from patients with gastroenteritis in the NWA region.