ArticleInfection and immunity2003
Disruption of epithelial barrier integrity by Salmonella enterica serovar typhimurium requires geranylgeranylated proteins.
Article in Infection and immunity, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 84 citations in OpenAlex.
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- Anthrax ET activates Rac1 and RTK signaling to induce F-actin reorganization and endothelial permeability.iScience · 2025Article
- Impact of protein prenylation inhibition onJournal of bacteriology · 2025Article
- The Prophylactic Protection of Salmonella Typhimurium Infection by Lentilactobacillus buchneri GX0328-6 in Mice.Probiotics and antimicrobial proteins · 2024Article
- The immune interactions of gut glycans and microbiota in health and disease.Molecular microbiology · 2024Review
- Salmonella engages CDC42 effector protein 1 for intracellular invasion.Journal of cellular physiology · 2024Article
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- Understanding the Mechanism of Antimicrobial Resistance and Pathogenesis ofMicroorganisms · 2022Review
- Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways.Journal of clinical medicine · 2022Review
- Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework.Journal of clinical medicine · 2022Review
- Viral infectious diseases severity: co-presence of transcriptionally active microbes (TAMs) can play an integral role for disease severity.Frontiers in immunology · 2022Review
- A Novel Adult Murine Model of Typical EnteroaggregativeFrontiers in cellular and infection microbiology · 2022Article
- Immunization of Broiler Chickens With a Killed Chitosan NanoparticleFrontiers in physiology · 2022Article
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- The Exopolysaccharide Produced byMicroorganisms · 2021Article
- Evaluation of curcumin and copper acetate against Salmonella Typhimurium infection, intestinal permeability, and cecal microbiota composition in broiler chickens.Journal of animal science and biotechnology · 2021Article
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- Impaired Intestinal Barrier and Tissue Bacteria: Pathomechanisms for Metabolic Diseases.Frontiers in endocrinology · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial cells that line the human intestinal mucosa constitute the initial sites of host invasion by bacterial pathogens. A number of bacteria, such as Salmonella and Yersinia spp., have been shown to disrupt the integrity of the epithelial barrier, although little is known about the mechanisms underlying that effect. We found that polarized MDCK-1 epithelial cells infected with invasive Salmonella enterica serovar Typhimurium SL1344 exhibited marked changes in F-actin organization, an increase in the paracellular flux of dextran, and a rapid decrease in transepithelial electrical resistance (TER). In contrast, infection with an isogenic noninvasive mutant (hilA) increased the TER in these cells. Pretreating MDCK-1 cells with the inhibitors for tyrosine kinase (genistein) or phosphatidylinositol 3-kinase (wortmannin) did not affect invasion and subsequent perturbation of the epithelial barrier by serovar Typhimurium. Instead, the geranylgeranyltransferase 1 inhibitor GGTI-298, but not the farnesyltransferase inhibitor FTI-277, clearly reversed the capacity of serovar Typhimurium to disrupt the epithelial barrier. The substrates for GGTI-298 include Rho family GTPases, as indicated by inhibiting prenylation of Rac1 and Cdc42. Infection with wild-type serovar Typhimurium increased the level of activated Rac1 and Cdc42 and caused these proteins to accumulate apically in MDCK-1 cells. This Salmonella-induced accumulation of Rac1 and Cdc42 and alteration of the junction-associated proteins ZO-1, occludin, and E-cadherin in MDCK-1 cells were markedly inhibited by GGTI-298. These results suggest that activation of geranylgeranylated proteins, including Rac1 and Cdc42, is critical for disruption of barrier integrity by serovar Typhimurium in polarized MDCK-1 cells.
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