Association of small Rho GTPases and actin ring formation in epithelial cells during the invasion by<i>Candida albicans</i>

Atre, Ashwini; Surve, Sachin V.; Shouche, Yogesh S.; Joseph, Jomon; Patole, Milind S.; Deopurkar, R. L.

doi:10.1111/j.1574-695x.2008.00504.x

Cited by 17 publications

(14 citation statements)

References 39 publications

(40 reference statements)

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“…5B, inhibition of Rac1 significantly decreased the percent relative R. montanensis invasion of tick cells compared to that in the untreated control by 38% (P Ͻ 0.0001) at a 1 mM concentration of the inhibitor used. Consistently with the suggested role of Rac in R. parkeri, L. monocytogenes, and Candida albicans invasion of mammalian and Drosophila cells (9,43,53), Rac1 inhibition correlates with R. montanensis infection in tick cells. In contrast, experiments employing dominant negative Rac1 mutants suggested that Rac was not involved in R. conorii invasion of Vero cells (6).…”

Section: Fig 3 Arp2/3 Complex Is Important For Rickettsial Internalizsupporting

confidence: 52%

Identification of Host Proteins Involved in Rickettsial Invasion of Tick Cells

et al. 2015

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Tick-borne spotted fever group (SFG) Rickettsia species are obligate intracellular bacteria capable of infecting both vertebrate and invertebrate host cells, an essential process for subsequent bacterial survival in distinct hosts. The host cell signaling molecules involved in the uptake of Rickettsia into mammalian and Drosophila cells have been identified; however, invasion into tick cells is understudied. Considering the movement of SFG Rickettsia between vertebrate and invertebrate hosts, the hypothesis is that conserved mechanisms are utilized for host cell invasion. The current study employed biochemical inhibition assays to determine the tick proteins involved in Rickettsia montanensis infection of tick-derived cells from a natural host, Dermacentor variabilis. The results revealed several tick proteins important for rickettsial invasion, including actin filaments, actin-related protein 2/3 complex, phosphatidylinositol-3=-kinase, protein tyrosine kinases (PTKs), Src family PTK, focal adhesion kinase, Rho GTPase Rac1, and neural Wiskott-Aldrich syndrome protein. Delineating the molecular mechanisms of rickettsial infection is critical to a thorough understanding of rickettsial transmission in tick populations and the ecology of tick-borne rickettsial diseases.T ick-borne rickettsial diseases caused by pathogenic bacteria belonging to the genera Rickettsia, Anaplasma, and Ehrlichia are steadily increasing in the United States (1). Infection associated with these obligate intracellular bacteria ranges from mild, self-limiting to severe, including death (2). In the typical transmission cycle, spotted fever group (SFG) rickettsiae transmit vertically during the tick life cycle stages and between vectors and vertebrate hosts during tick acquisition of a blood meal. In vertebrate hosts, mechanisms of SFG Rickettsia infection, including invasion, escape from the phagosome, intracellular growth, intracellular movement, and cell-to-cell spread, have been studied (3). Tick acquisition of SFG Rickettsia from rickettsemic hosts is poorly described, and despite the essential role for tick hosts in maintenance and transmission of SFG Rickettsia to vertebrate hosts, the biology of the tick cell-SFG Rickettsia interaction is understudied.The obligate intracellular nature of Rickettsia requires bacteria to invade both vertebrate and invertebrate host cells, and this process, host cell invasion by SFG Rickettsia, has been studied in mammalian and Drosophila cell lines. Mammalian ligands Ku70 and ␣ 2 ␤ 1 integrin interact with rickettsial outer membrane proteins B and A (OmpB and OmpA), respectively, and are involved in Rickettsia conorii invasion of mammalian host cells (4, 5). After binding to rickettsial OmpB, R. conorii induces signaling cascades in which Ku70 is initially ubiquitinated by c-Cbl ubiquitin ligase. Subsequently, signaling molecules, including Cdc42, protein tyrosine kinases (PTKs), phosphatidylinositol-3=-kinase (PI3-kinase), Src family tyrosine kinases (Src), focal adhesion kinase (FAK), and cortactin, c...

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Section: Fig 3 Arp2/3 Complex Is Important For Rickettsial Internalizsupporting

confidence: 52%

Identification of Host Proteins Involved in Rickettsial Invasion of Tick Cells

et al. 2015

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“…In C. albicans , small GTPases such as Cdc42 and Ras1 have been extensively investigated for their roles in regulating hyphal growth and tissue invasion111220212223. To unravel novel gene functions, we have constructed a haploid gene-deletion library covering mostly genes encoding uncharacterized GTPases and their regulators listed in the Candida Genome database (manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

New “haploid biofilm model” unravels IRA2 as a novel regulator of Candida albicans biofilm formation

Seneviratne

Zeng

Truong

et al. 2015

Sci Rep

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Clinical isolates of the fungal human pathogen Candida albicans are invariably diploid and heterozygous, impeding genetic study. Recent isolation of C. albicans haploids opens opportunities to apply technologies unfeasible in diploids. However, doubts remain on whether the haploids, derived from chromosome loss, can represent the diploids. Here, we use C. albicans haploids to investigate biofilm, a key virulence attribute. We conducted the first comprehensive characterization of biofilm formation of the haploids in comparison with the diploids. We demonstrate that the haploids form biofilms with essentially the same characteristics as the diploids. Screening a haploid mutant library has uncovered novel GTPase-related genes as biofilm regulators, including IRA2 that encodes an activator of the Ras GTPase. IRA2-deletion mutants develop poorly constructed biofilm in both haploid and diploid C. albicans. Our results demonstrate that the haploids are a valid model for C. albicans biofilm research and a powerful tool for uncovering novel regulators.

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“…In contrast, Chlamydia trachomatis requires solely Rac for internalization [30]. In other cases, a combination of two GTPases allows invasion, as in the case of Candida albicans that needs Rho and Rac to modulate actin cytoskeleton organization [31]. Specific inhibitors and expression of dominant-negative derivatives demonstrated that the Rck-mediated entry process was dependent on the mobilization of actin microfilaments that were activated by the signaling Arp2/3 complex and the GTPases Rac and Cdc42, but not by Rho.…”

Section: Discussionmentioning

confidence: 99%

Rck of Salmonella enterica, subspecies enterica serovar Enteritidis, mediates Zipper-like internalization

et al. 2010

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Salmonella can invade non-phagocytic cells through its type III secretion system (T3SS-1), which induces a Trigger entry process. This study showed that Salmonella enterica, subspecies enterica serovar Enteritidis can also invade cells via the Rck outer membrane protein. Rck was necessary and sufficient to enable non-invasive E. coli and Rckcoated beads to adhere to and invade different cells. Internalization analysis of latex beads coated with different Rck peptides showed that the peptide containing amino acids 140-150 promoted adhesion, whereas amino acids between 150 and 159 modulated invasion. Expression of dominant-negative derivatives and use of specific inhibitors demonstrated the crucial role of small GTPases Rac1 and Cdc42 in activating the Arp2/3 complex to trigger formation of actin-rich accumulation, leading to Rck-dependent internalization. Finally, scanning and transmission electron microscopy with Rck-coated beads and E. coli expressing Rck revealed microvillus-like extensions that formed a Zipper-like structure, engulfing the adherent beads and bacteria. Overall, our results provide new insights into the Salmonella T3SS-independent invasion mechanisms and strongly suggest that Rck induces a Zipper-like entry mechanism. Consequently, Salmonella seems to be the first bacterium found to be able to induce both Zipper and Trigger mechanisms to invade host cells.

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Association of small Rho GTPases and actin ring formation in epithelial cells during the invasion byCandida albicans

Cited by 17 publications

References 39 publications

Identification of Host Proteins Involved in Rickettsial Invasion of Tick Cells

Identification of Host Proteins Involved in Rickettsial Invasion of Tick Cells

New “haploid biofilm model” unravels IRA2 as a novel regulator of Candida albicans biofilm formation

Rck of Salmonella enterica, subspecies enterica serovar Enteritidis, mediates Zipper-like internalization

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