Cell Biology of Bacterial Infections
We focus on host-pathogen interactions and investigate cell biology processes and signaling pathways involved in pathogen-induced host cytoskeleton remodeling.
We use several human bacterial pathogens and purified toxins to uncover the mechanisms underlying 1) bacterial usurpation of host cytoskeleton function and 2) host resistance and survival to infection.
While the pathogen exploits cellular functions to hide from immune defense and establish within the host, the host deploys resistance mechanisms to repair damage and survive to infection. We have been studying the Listeria monocytogenes infectious process and the host responses to intoxication by bacterial pore-forming toxins.
In particular, we assessed host cytoskeleton alterations induced during intracellular infection by Listeria monocytogenes and upon intoxication with purified pore-forming toxins, which are major virulence factors of human bacterial pathogens. We have found that during infection of epithelial cells, L. monocytogenes exploits the function of actomyosin, keratins and tubulin to promote cellular invasion and cell-to-cell spread. In addition, we showed that upon plasma membrane damage induced by pore-forming toxins, human epithelial cells undergo massive actomyosin remodeling. The assembly of cortical actomyosin structures in the target cell appears to be critical to plasma membrane repair, recovery of cell integrity and host survival to infection.
- J. Leong, Tufts University, Boston-USA
- A. Lacy-Hulbert, Benaroya Research Institute, Seattle-USA
- S. Mostowy, Imperial College, London-UK
- J. Sellers, NIH-NHLBI, Bethesda-USA
- D. Cabanes, IBMC/i3S, Porto-Portugal
- A. X. Carvalho, IBMC/i3S, Porto-Portugal
- POCI-01-0145-FEDER-030863 - Enlighten host plasma membrane repair mechanisms upon bacterial pore-forming toxins attack
- NORTE-01-0145-FEDER-000012 – Structured Program on Bioengineered Therapies for Infectious Diseases and Tissue Regeneration
Stathmin recruits tubulin to Listeria monocytogenes-induced actin comets and promotes bacterial dissemination. Cellular and Molecular Life Sciences76(5):961-975, 2019. [Journal: Article] [CI: 2] [IF: 6,5]
DOI: 10.1007/s00018-018-2977-7 SCOPUS: 85057542589. .
Brito C., Cabanes D., Sarmento Mesquita F., Sousa S.,
Mechanisms protecting host cells against bacterial pore-forming toxins. Cellular and Molecular Life Sciences76(7):1319-1339, 2019. [Journal: Review] [CI: 19] [IF: 6,5]
DOI: 10.1007/s00018-018-2992-8 SCOPUS: 85059153781. .
Pinheiro J., Lisboa J., Pombinho R., Carvalho F., Carreaux A., Brito C., Pöntinen A., Korkeala H., Dos Santos N.M.S., Morais-Cabral J.H., Sousa S., Cabanes D.,
MouR controls the expression of the Listeria monocytogenes Agr system and mediates virulence. Nucleic Acids Research46(18):9338-9352, 2018. [Journal: Article] [CI: 10] [IF: 11,1]
DOI: 10.1093/nar/gky624 SCOPUS: 85054896319. .
Cruz R., Pereira-Castro I., Almeida M.T., Moreira A., Cabanes D., Sousa S.,
Epithelial keratins modulate cMet expression and signaling and promote InlB-mediated Listeria monocytogenes infection of HeLa cells. Frontiers in Cellular and Infection Microbiology8(MAY):, 2018. [Journal: Article] [CI: 6] [IF: 3,5]
DOI: 10.3389/fcimb.2018.00146 SCOPUS: 85046878080. .
Mesquita F.S., Brito C., Mazon Moya M.J., Pinheiro J.C., Mostowy S., Cabanes D., Sousa S.,
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins. EMBO Reports18(2):303-318, 2017. [Journal: Article] [CI: 9] [IF: 8,7]
DOI: 10.15252/embr.201642833 SCOPUS: 85007487818. .
do Vale A., Cabanes D., Sousa S.,
Bacterial toxins as pathogen weapons against phagocytes. Frontiers in Microbiology7(FEB):, 2016. [Journal: Review] [CI: 32] [IF: 4,1]
DOI: 10.3389/fmicb.2016.00042 SCOPUS: 84962082244. .
Almeida M.T., Mesquita F.S., Cruz R., Osório H., Custódio R., Brito C., Vingadassalom D., Martins M., Leong J.M., Holden D.W., Cabanes D., Sousa S.,
Src-dependent tyrosine phosphorylation of non-muscle myosin heavy chain-IIA restricts Listeria monocytogenes cellular infection. Journal of Biological Chemistry290(13):8383-8395, 2015. [Journal: Article] [CI: 11] [IF: 4,3]
DOI: 10.1074/jbc.M114.591313 SCOPUS: 84925760833. .
Leitão E., Costa A.C., Brito C., Costa L., Pombinho R., Cabanes D., Sousa S.,
Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection. Cell Cycle13(6):928-940, 2014. [Journal: Article] [CI: 21] [IF: 4,6]
DOI: 10.4161/cc.27780 SCOPUS: 84897994129. .
Martins M., Custodio R., Camejo A., Almeida M.T., Cabanes D., Sousa S.,
Listeria monocytogenes triggers the cell surface expression of Gp96 protein and interacts with its N terminus to support cellular infection. Journal of Biological Chemistry287(51):43083-43093, 2012. [Journal: Article] [CI: 19] [IF: 4,7]
DOI: 10.1074/jbc.M112.422568 SCOPUS: 84871163192. .