Gustavo Caballero-Flores

Education

PhD: National Autonomous University of Mexico (UNAM), Mexico.

Other: Postdoctoral Fellow, Dr. Gabriel Nunez’s lab, University of Michigan, USA.

Research Summary

Our research focuses on the mechanisms leading to the establishment, progression and resolution of enteric and systemic infection in highly susceptible individuals, including children and immunocompromised patients. Specifically, we seek to understand the virulence strategies by which bacterial pathogens establish infection under different host conditions, leading to distinct disease severity and outcome. We are also interested in the mechanisms by which the gut microbiota and host immune responses prevent or promote pathogen colonization. To address these points, we primarily use mouse models with different age, genetic background and/or microbiota composition, as well as methods from microbiology, immunology, and high-throughput technologies.

Research Detail

We are currently working in the following projects:

• Pathogen evasion of colonization resistance in the gut.

We reported that depletion of amino acids by the gut microbiota limits intestinal colonization by Citrobacter rodentium, a mouse pathogen that models human enteric infection with the closely related pathogens enteropathogenic and enterohemorrhagic Escherichia coli. In turn, we also found that pathogen induction of amino acid biosynthesis, or an increased intake of dietary amino acids, promote pathogen colonization in the gut. However, the role of conserved or strain-specific genetic factors in other pathogens during early intestinal expansion, and the differential colonization resistance conferred by the microbiota at distinct sites along the gastrointestinal tract, remain to be further explored.

• Host susceptibility factors to severe enteric infection during early life.

As observed for enteropathogenic E. coli human infections, young mice are also more susceptible to C. rodentium enteric infection than adult animals. The young mouse model of disease shows acute diarrhea, marked pathogen translocation, and lethality. In contrast, adult animals exhibit only a mild, self-limiting disease that is fully resolved a few weeks after infection. However, the mechanisms underlying the increased susceptibility to enteric infection in the young group remain poorly understood. We are interested in identifying immune, microbiota or other host factors contributing to severe enteric disease in the neonatal gut, aiming to harness them to promote protection during early life.

• Pathogen adaptation to different host environments.

Various enteric pathogens can translocate from the gut to the systemic circulation and cause bacteremia in susceptible individuals. However, the virulence strategies allowing bacterial pathogens to disseminate and/or thrive in different host environments outside the gut remain poorly understood. We are interested in identifying pathogen factors promoting niche adaptation during distinct types or stages of infection in the host. This might lead to the discovery of new antimicrobial targets and/or the development of better treatment strategies for both enteric and systemic infections in humans.

Publications

https://pubmed.ncbi.nlm.nih.gov/?term=Caballero-Flores+Gustavo&sort=date