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 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.

Gene expression changes during Giardia–host cell interactions in serum-free medium

2014 ◽  
Vol 197 (1-2) ◽  
pp. 21-23 ◽  
Author(s):  
Marcela Ferella ◽  
Barbara J. Davids ◽  
Michael J. Cipriano ◽  
Shanda R. Birkeland ◽  
Daniel Palm ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Cell Interactions ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free ◽  
Host Cell Interactions

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 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.

scholarly journals Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

2013 ◽  
Vol 20 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Katherine H. Restori ◽  
Mary J. Kennett ◽  
A. Catharine Ross
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Expression Profiles ◽  
Cytokine Gene Expression ◽  
Dependent Manner ◽  
Pneumonia Severity ◽  
Content Type ◽  
Amyloid A

ABSTRACTVaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positiveStreptococcus pneumoniaeserotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum.

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