Francisco García del Portillo
Group Leader
Research summary
We have progressed in the characterization of small regulatory RNA expressed by non-growing intracellular Salmonella on infection of cultured fibroblasts. Some of these sRNA were found to be upregulated in intracellular bacteria only at late post-infection times. This expression pattern suggests that a subset of sRNA might play a role in long-adaptation of intracellular bacteria to limited nutrient availability and stress.
Publications
Castanheira S, Cestero JJ, Rico-Pérez G, García P, Cava F, Ayala JA, Pucciarelli MG, García-Del Portillo F. A Specialized Peptidoglycan Synthase Promotes Salmonella Cell Division inside Host Cells. MBio. 2017 Dec 19;8(6)
Impens F, Rolhion N, Radoshevich L, Bécavin C, Duval M, Mellin J, García Del Portillo F, Pucciarelli MG, Williams AH, Cossart P. N-terminomics identifies Prli42 as a membrane miniprotein conserved in Firmicutes and critical for stressosome activation in Listeria monocytogenes. Nat Microbiol. 2017 Feb 13; 2:17005
López-Montero N, Ramos-Marquès E, Risco C, García-Del Portillo F. Intracellular Salmonella induces aggrephagy of host endomembranes in persistent infections. Autophagy. 2016 Oct 2;12(10):1886-1901.
Lobato-Márquez D, Díaz-Orejas R, García-Del Portillo F. Toxin-antitoxins and bacterial virulence. FEMS Microbiol Rev. 2016 Sep;40(5):592-609.
Ramos-Marquès E, Zambrano S, Tiérrez A, Bianchi ME, Agresti A, García-Del Portillo F. Single-cell analyses reveal an attenuated NF-κB response in the Salmonella-infected fibroblast. Virulence. 2016 Aug 30:1-22.
Funding
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Programa Nacional de cooperación Público-Privada (Subprograma INNPACTO) IPT-2012-0213-060000: Tecnologías innovadoras para el desarrollo de nuevos productos saludables a base de polifenoles (INNOFENOL) |
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Our group studies two “model” intracellular bacterial pathogens important in human and animal health, Listeria monocytogenes and Salmonella enterica serovar Typhimurium. These bacteria have different cell wall architecture and adopt distinct lifestyles (cytosol versus intra-vacuolar) within the eukaryotic cell. The common aim of our studies is to identify envelope changes during host cell colonisation and to understand how these changes shape the course of infection.
Listeria monocytogenes. This pathogen produces a large number of surface proteins, many exclusive to this bacterium and with unknown function. A family of surface proteins of particular interest to us is that composed of proteins covalently bound to the peptidoglycan after processing of their LPXTG-sorting motif. We have linked the biological function of two L. monocytogenes LPXTG surface proteins, Lmo0412 and Lmo1413, to bacteria interaction with the host. Lack of either protein alters virulence in the mouse model. In addition, we dissected the mechanism used by intracellular L. monocytogenes to upregulate the LPXTG protein Lmo0514 inside host cells. This mechanism involves the regulatory small RNA (sRNA) Rli27 and a long 5’-UTR present in a defined lmo0514 mRNA transcript isoform. We are currently pursuing the biological role of Lmo0514 inside host cells.
S. enterica serovar Typhimurium. This pathogen establishes persistent infections in which bacteria reside in a “dormant-like” state within eukaryotic cells. The molecular basis of this phenomenon is poorly understood. Using the fibroblast S. enterica Typhimurium infection model, we characterised the expression of numerous regulatory sRNAs in non-proliferating intracellular bacteria, and identified an sRNA species induced in these conditions. We also examined the role of toxin-antitoxin (TA) modules, which respond to many stresses, in establishing persistent infections inside eukaryotic cells. These studies showed an unexpectedly large number of TA modules in S. enterica Typhimurium and the selective use of some in distinct host cell types. We continued our studies on the enzymatic machinery that supports peptidoglycan metabolism in intracellular bacteria and those focused on peptidoglycan sensing during persistent infection. Lastly, we have linked S. Typhimurium persistence to a type of autophagy not previously reported in bacterial infections.
