Host cell invasion mediated by Trypanosoma cruzi surface molecule gp82 is associated with F-actin disassembly and is inhibited by enteroinvasive Escherichia coli |
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Authors: | Cortez Mauro Atayde Vanessa Yoshida Nobuko |
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Institution: | 1. Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA;2. School of Life Sciences, Arizona State University, Tempe, AZ, USA;1. College of Pharmacy, Belmont University, Nashville, TN 37212, USA;2. Department of Pain Management, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210011, China;3. Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang 110004, China;4. Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA;5. Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA;6. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;7. Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA;8. Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;9. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;1. CODA-CERVA, Coordination of Veterinary Diagnostics Epidemiology and Risk Analysis, Groeselenberg 99, 1180 Brussels, Belgium;2. CODA-CERVA, Operational Directorate Viral Diseases, Groeselenberg 99, 1180 Brussels, Belgium;3. CODA-CERVA, Experimental Center, Kerklaan 62, 1830 Machelen, Belgium;1. Department of Computer Science, The College of New Jersey, Ewing, NJ 08628, United States;2. Department of Computer Science, New York College, Athens, Greece;1. Department of Pathology, Albert Einstein College of Medicine, NY, USA;2. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, NY, USA;3. Department of Physiology, Presidency University, Kolkata, India;4. Department of Genetics, Albert Einstein College of Medicine, NY, USA;5. Program in Health Sciences, Infectious Diseases and Tropical Medicine/Interdisciplinary, Laboratory of Medical Investigation, Faculty of Medicine, and the Department of Biochemistry and Immunology, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;6. Division of Perinatal Research, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, N.S.W., Australia;7. Department of Medicine, Albert Einstein College of Medicine, NY, USA |
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Abstract: | The target cell F-actin disassembly, induced by a Ca2+-signaling Trypanosoma cruzi factor of unknown molecular identity, has been reported to promote parasite invasion. We investigated whether the metacyclic trypomastigote stage-specific surface molecule gp82, a Ca2+-signal-inducing molecule implicated in host cell invasion, displayed the ability to induce actin cytoskeleton disruption, using a recombinant protein (J18) containing the full-length gp82 sequence fused to GST. J18, but not GST, induced F-actin disassembly in HeLa cells, significantly reducing the number as well as the length of stress fibers. The number of cells with typical stress fibers scored approximately 70% in untreated and GST-treated cells, as opposed to approximately 30% in J18-treated samples, which also showed decreased F-actin content. J18, but not GST, inhibited approximately 6-fold the HeLa cell entry of enteroinvasive Escherichia coli (EIEC), which depends on actin cytoskeleton. Not only were fewer cells infected with bacteria in the presence of J18, there were also fewer bacteria per cell. The inhibitory activity of J18 was Ca2+ dependent. In co-infection experiments, preincubation of HeLa cells with EIEC drastically reduced gp82-dependent internalization of T. cruzi metacyclic forms. All these data, plus the finding that gp82-mediated penetration of metacyclic forms was associated with disrupted HeLa cell cytoskeletal architecture, indicate that gp82 promotes parasite invasion by disassembling the cortical actin cytoskeleton. |
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