scholarly journals Role of Retrograde Trafficking in Stress Response, Host Cell Interactions, and Virulence of Candida albicans

2013 ◽  
Vol 13 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Yaoping Liu ◽  
Norma V. Solis ◽  
Clemens J. Heilmann ◽  
Quynh T. Phan ◽  
Aaron P. Mitchell ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Host Cell ◽  
Signaling Pathway ◽  
Stress Resistance ◽  
Cell Interactions ◽  
Content Type ◽  
Retrograde Trafficking ◽  
Host Cell Interactions ◽  
Vacuolar Protein ◽  
Calcineurin Signaling

ABSTRACTInSaccharomyces cerevisiae, the vacuolar protein sorting complexes Vps51/52/53/54 and Vps15/30/34/38 are essential for efficient endosome-to-Golgi complex retrograde transport. Here we investigated the function of Vps15 and Vps51, representative members of these complexes, in the stress resistance, host cell interactions, and virulence ofCandida albicans. We found thatC. albicansvps15Δ/Δ andvps51Δ/Δ mutants had abnormal vacuolar morphology, impaired retrograde protein trafficking, and dramatically increased susceptibility to a variety of stressors. These mutants also had reduced capacity to invade and damage oral epithelial cellsin vitroand attenuated virulence in the mouse model of oropharyngeal candidiasis. Proteomic analysis of the cell wall of thevps51Δ/Δ mutant revealed increased levels of the Crh11 and Utr2 transglycosylases, which are targets of the calcineurin signaling pathway. The transcript levels of the calcineurin pathway membersCHR11,UTR2,CRZ1,CNA1, andCNA2were elevated in thevps15Δ/Δ andvps51Δ/Δ mutants. Furthermore, these strains were highly sensitive to the calcineurin-specific inhibitor FK506. Also, deletion ofCHR11andUTR2further increased the stress susceptibility of these mutants. In contrast, overexpression ofCRH11andUTR2partially rescued their defects in stress resistance, but not host cell interactions. Therefore, intact retrograde trafficking inC. albicansis essential for stress resistance, host cell interactions, and virulence. Aberrant retrograde trafficking stimulates the calcineurin signaling pathway, leading to the increased expression of Chr11 and Utr2, which enablesC. albicansto withstand environmental stress.

scholarly journals Identification and Characterization of Cryptosporidium parvum Clec, a Novel C-Type Lectin Domain-Containing Mucin-Like Glycoprotein

2013 ◽  
Vol 81 (9) ◽  
pp. 3356-3365 ◽  
Author(s):  
Seema Bhalchandra ◽  
Jacob Ludington ◽  
Isabelle Coppens ◽  
Honorine D. Ward
Keyword(s):  
Host Cell ◽  
Transmembrane Domain ◽  
Cell Interactions ◽  
Apical Region ◽  
Content Type ◽  
Lectin Domain ◽  
Loop Region ◽  
Wide Range ◽  
Host Cell Interactions

ABSTRACTCryptosporidiumspecies are waterborne apicomplexan parasites that cause diarrheal disease worldwide. Although the mechanisms underlyingCryptosporidium-host cell interactions are not well understood, mucin-like glycoproteins of the parasite are known to mediate attachment and invasionin vitro. We identifiedC. parvumClec (CpClec), a novel mucin-like glycoprotein that contains a C-type lectin domain (CTLD) and has orthologs inC. hominisandC. muris. CTLD-containing proteins are ligand-binding proteins that function in adhesion and signaling and are present in a wide range of organisms, from humans to viruses. However, this is the first report of a CTLD-containing protein in protozoa and inApicomplexa. CpClec is predicted to be a type 1 membrane protein, with a CTLD, an O-glycosylated mucin-like domain, a transmembrane domain, and a cytoplasmic tail containing a YXXϕ sorting motif. The predicted structure ofCpClec displays several characteristics of canonical CTLD-containing proteins, including a long loop region hydrophobic core associated with calcium-dependent glycan binding as well as predicted calcium- and glycan-binding sites.CpClec expression duringC. parvuminfectionin vitrois maximal at 48 h postinfection, suggesting that it is developmentally regulated. The 120-kDa mass of nativeCpClec is greater than predicted, most likely due to O-glycosylation.CpClec is localized to the surface of the apical region and to dense granules of sporozoites and merozoites. Taken together, these findings, along with the known functions ofC. parvummucin-like glycoproteins and of CTLD-containing proteins, strongly implicate a significant role forCpClec inCryptosporidium-host cell interactions.

scholarly journals Farnesol Induces Hydrogen Peroxide Resistance in Candida albicans Yeast by Inhibiting the Ras-Cyclic AMP Signaling Pathway

2010 ◽  
Vol 9 (4) ◽  
pp. 569-577 ◽  
Author(s):  
Aurélie Deveau ◽  
Amy E. Piispanen ◽  
Angelyca A. Jackson ◽  
Deborah A. Hogan
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Candida Albicans ◽  
Adenylate Cyclase ◽  
Signaling Pathway ◽  
Stress Resistance ◽  
Ros Generation ◽  
Signaling Molecule ◽  
Content Type ◽  
Oxidative Stress Resistance

ABSTRACT Farnesol, a Candida albicans cell-cell signaling molecule that participates in the control of morphology, has an additional role in protection of the fungus against oxidative stress. In this report, we show that although farnesol induces the accumulation of intracellular reactive oxygen species (ROS), ROS generation is not necessary for the induction of catalase (Cat1)-mediated oxidative-stress resistance. Two antioxidants, α-tocopherol and, to a lesser extent, ascorbic acid effectively reduced intracellular ROS generation by farnesol but did not alter farnesol-induced oxidative-stress resistance. Farnesol inhibits the Ras1-adenylate cyclase (Cyr1) signaling pathway to achieve its effects on morphology under hypha-inducing conditions, and we demonstrate that farnesol induces oxidative-stress resistance by a similar mechanism. Strains lacking either Ras1 or Cyr1 no longer exhibited increased protection against hydrogen peroxide upon preincubation with farnesol. While we also observed the previously reported increase in the phosphorylation level of Hog1, a known regulator of oxidative-stress resistance, in the presence of farnesol, the hog1/hog1 mutant did not differ from wild-type strains in terms of farnesol-induced oxidative-stress resistance. Analysis of Hog1 levels and its phosphorylation states in different mutant backgrounds indicated that mutation of the components of the Ras1-adenylate cyclase pathway was sufficient to cause an increase of Hog1 phosphorylation even in the absence of farnesol or other exogenous sources of oxidative stress. This finding indicates the presence of unknown links between these signaling pathways. Our results suggest that farnesol effects on the Ras-adenylate cyclase cascade are responsible for many of the observed activities of this fungal signaling molecule.

scholarly journals Pivotal Roles for Ribonucleases in Streptococcus pneumoniae Pathogenesis

mBio ◽  
2021 ◽  
Author(s):  
Dhriti Sinha ◽  
Jacob P. Frick ◽  
Kristen Clemons ◽  
Malcolm E. Winkler ◽  
Nicholas R. De Lay
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Host Cell ◽  
Cell Interactions ◽  
Human Pathogen ◽  
Protein Coding ◽  
Content Type ◽  
Key Players ◽  
Host Cell Interactions ◽  
Host Tissues

Streptococcus pneumoniae is a notorious human pathogen that adapts to conditions in distinct host tissues and responds to host cell interactions by adjusting gene expression. RNases are key players that modulate gene expression by mediating the turnover of regulatory and protein-coding transcripts.

scholarly journals Chlamydia trachomatis Polymorphic Membrane Protein D Is a Virulence Factor Involved in Early Host-Cell Interactions

2014 ◽  
Vol 82 (7) ◽  
pp. 2756-2762 ◽  
Author(s):  
Laszlo Kari ◽  
Timothy R. Southern ◽  
Carey J. Downey ◽  
Heather S. Watkins ◽  
Linnell B. Randall ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Membrane Protein ◽  
Host Cell ◽  
Virulence Factor ◽  
Reverse Genetics ◽  
Cell Interactions ◽  
Infection Model ◽  
Null Mutant ◽  
Content Type ◽  
Host Cell Interactions

ABSTRACTChlamydia trachomatisis an obligate intracellular mucosotropic pathogen of significant medical importance. It is the etiological agent of blinding trachoma and bacterial sexually transmitted diseases, infections that afflict hundreds of millions of people globally. TheC. trachomatispolymorphic membrane protein D (PmpD) is a highly conserved autotransporter and the target of broadly cross-reactive neutralizing antibodies; however, its role in host-pathogen interactions is unknown. Here we employed a targeted reverse genetics approach to generate apmpDnull mutant that was used to define the role of PmpD in the pathogenesis of chlamydial infection. We show thatpmpDis not an essential chlamydial gene and thepmpDnull mutant has no detectable deficiency in cultured murine cells or in a murine mucosal infection model. Notably, however, thepmpDnull mutant was significantly attenuated for macaque eyes and cultured human cells. A reduction inpmpDnull infection of human endocervical cells was associated with a deficiency in chlamydial attachment to cells. Collectively, our results show that PmpD is a chlamydial virulence factor that functions in early host-cell interactions. This study is the first of its kind using reverse genetics to evaluate the contribution of aC. trachomatisgene to disease pathogenesis.

scholarly journals Capsular polysaccharide switching in Streptococcus suis modulates host cell interactions and virulence

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masatoshi Okura ◽  
Jean-Philippe Auger ◽  
Tomoyuki Shibahara ◽  
Guillaume Goyette-Desjardins ◽  
Marie-Rose Van Calsteren ◽  
...  
Keyword(s):  
Host Cell ◽  
Capsular Polysaccharide ◽  
Inflammatory Mediator ◽  
Streptococcus Suis ◽  
Cell Interactions ◽  
Inflammatory Mediator Production ◽  
Composition And Structure ◽  
Infection Models ◽  
Host Cell Interactions ◽  
Blood Dendritic Cell

AbstractThe capsular polysaccharide (CPS) of Streptococcus suis defines various serotypes based on its composition and structure. Though serotype switching has been suggested to occur between S. suis strains, its impact on pathogenicity and virulence remains unknown. Herein, we experimentally generated S. suis serotype-switched mutants from a serotype 2 strain that express the serotype 3, 4, 7, 8, 9, or 14 CPS. The effects of serotype switching were then investigated with regards to classical properties conferred by presence of the serotype 2 CPS, including adhesion to/invasion of epithelial cells, resistance to phagocytosis by macrophages, killing by whole blood, dendritic cell-derived pro-inflammatory mediator production and virulence using mouse and porcine infection models. Results demonstrated that these properties on host cell interactions were differentially modulated depending on the switched serotypes, although some different mutations other than loci of CPS-related genes were found in each the serotype-switched mutant. Among the serotype-switched mutants, the mutant expressing the serotype 8 CPS was hyper-virulent, whereas mutants expressing the serotype 3 or 4 CPSs had reduced virulence. By contrast, switching to serotype 7, 9, or 14 CPSs had little to no effect. These findings suggest that serotype switching can drastically alter S. suis virulence and host cell interactions.

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