Streptococcus suis small RNA rss04 contributes to the induction of meningitis by regulating capsule synthesis and by inducing biofilm formation in a mouse infection model

Abstract Backgrounds Primary infection with Toxoplasma gondii during pregnancy can pose serious health problems for the fetus. However, the epidemiological status of toxoplasmosis among reproductive-aged population in Myanmar is largely unknown. Although luciferase immunoprecipitation system (LIPS) assays for serodiagnosis of toxoplasmosis was developed mostly using mouse infection model, had not been tested by using field-derived human samples. Methods A total of 251 serum samples were collected from reproductive-aged women, residing in Shwegyin township, Bago region, Myanmar and analyzed with a commercial ELISA kit, as well as in-house LIPS assays. Results The overall seroprevalence for Toxoplasma gondii infection by the commercial ELISA was 11.5%. No clear risk factor was identified except for being in the younger age group (15–30 years old). Overall, LIPS assays showed low sensitivity when the commercial ELSA was used as a reference test. Conclusion We identified the epidemiological situation of toxoplasmosis in some rural communities in Myanmar. The data obtained here will serve as a primary information for the effort to reduce toxoplasmosis in this region. Although looked promising in the previous experiments with mouse infection model, we found that the reported LIPS procedures need further improvements to increase the sensitivities.

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Phenotypic and Molecular Biological Analysis of Polymycovirus AfuPmV-1M From Aspergillus fumigatus: Reduced Fungal Virulence in a Mouse Infection Model

Frontiers in Microbiology ◽

10.3389/fmicb.2020.607795 ◽

2020 ◽

Vol 11 ◽

Author(s):

Azusa Takahashi-Nakaguchi ◽

Erika Shishido ◽

Misa Yahara ◽

Syun-ichi Urayama ◽

Akihiro Ninomiya ◽

...

Keyword(s):

Aspergillus Fumigatus ◽

Sequence Similarity ◽

Infection Model ◽

Dsrna Segment ◽

High Sequence Similarity ◽

Fungal Virulence ◽

Mouse Infection Model ◽

Mouse Infection ◽

Macrophage Phagocytosis ◽

Free Strain

The filamentous fungal pathogen Aspergillus fumigatus is one of the most common causal agents of invasive fungal infection in humans; the infection is associated with an alarmingly high mortality rate. In this study, we investigated whether a mycovirus, named AfuPmV-1M, can reduce the virulence of A. fumigatus in a mouse infection model. AfuPmV-1M has high sequence similarity to AfuPmV-1, one of the polymycovirus that is a capsidless four-segment double-stranded RNA (dsRNA) virus, previously isolated from the genome reference strain of A. fumigatus, Af293. However, we found the isolate had an additional fifth dsRNA segment, referred to as open reading frame 5 (ORF5), which has not been reported in AfuPmV-1. We then established isogenic lines of virus-infected and virus-free A. fumigatus strains. Mycovirus infection had apparent influences on fungal phenotypes, with the virus-infected strain producing a reduced mycelial mass and reduced conidial number in comparison with these features of the virus-free strain. Also, resting conidia of the infected strain showed reduced adherence to pulmonary epithelial cells and reduced tolerance to macrophage phagocytosis. In an immunosuppressed mouse infection model, the virus-infected strain showed reduced mortality in comparison with mortality due to the virus-free strain. RNA sequencing and high-performance liquid chromatography (HPLC) analysis showed that the virus suppressed the expression of genes for gliotoxin synthesis and its production at the mycelial stage. Conversely, the virus enhanced gene expression and biosynthesis of fumagillin. Viral RNA expression was enhanced during conidial maturation, conidial germination, and the mycelial stage. We presume that the RNA or translation products of the virus affected fungal phenotypes, including spore formation and toxin synthesis. To identify the mycovirus genes responsible for attenuation of fungal virulence, each viral ORF was ectopically expressed in the virus-free KU strain. We found that the expression of ORF2 and ORF5 reduced fungal virulence in the mouse model. In addition, ORF3 affected the stress tolerance of host A. fumigatus in culture. We hypothesize that the respective viral genes work cooperatively to suppress the pathogenicity of the fungal host.

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Methionyl-tRNA synthetase inhibitor has potent in vivo activity in a novel Giardia lamblia luciferase murine infection model

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz567 ◽

2020 ◽

Vol 75 (5) ◽

pp. 1218-1227

Author(s):

Samantha A Michaels ◽

Han-Wei Shih ◽

Bailin Zhang ◽

Edelmar D Navaluna ◽

Zhongsheng Zhang ◽

...

Keyword(s):

Giardia Lamblia ◽

Trna Synthetase ◽

Luciferase Reporter ◽

Infection Model ◽

Cell Assay ◽

Mouse Infection Model ◽

Mouse Infection ◽

Methionyl Trna Synthetase

Abstract Background Methionyl-tRNA synthetase (MetRS) inhibitors are under investigation for the treatment of intestinal infections caused by Giardia lamblia. Objectives To properly analyse the therapeutic potential of the MetRS inhibitor 1717, experimental tools including a robust cell-based assay and a murine model of infection were developed based on novel strains of G. lamblia that employ luciferase reporter systems to quantify viable parasites. Methods Systematic screening of Giardia-specific promoters and luciferase variants led to the development of a strain expressing the click beetle green luciferase. Further modifying this strain to express NanoLuc created a dual reporter strain capable of quantifying parasites in both the trophozoite and cyst stages. These strains were used to develop a high-throughput cell assay and a mouse infection model. A library of MetRS inhibitors was screened in the cell assay and Compound-1717 was tested for efficacy in the mouse infection model. Results Cell viability in in vitro compound screens was quantified via bioluminescence readouts while infection loads in mice were monitored with non-invasive whole-animal imaging and faecal analysis. Compound-1717 was effective in clearing mice of Giardia infection in 3 days at varying doses, which was supported by data from enzymatic and phenotypic cell assays. Conclusions The new in vitro and in vivo assays based on luciferase expression by engineered G. lamblia strains are useful for the discovery and development of new therapeutics for giardiasis. MetRS inhibitors, as validated by Compound-1717, have promising anti-giardiasis properties that merit further study as alternative therapeutics.

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Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model

Pediatric Pulmonology ◽

10.1002/ppul.23956 ◽

2018 ◽

Vol 53 (5) ◽

pp. 567-574 ◽

Cited By ~ 10

Author(s):

Ricardo A. Mosquera ◽

Wilfredo De Jesus-Rojas ◽

James M. Stark ◽

Aravind Yadav ◽

Cindy K. Jon ◽

...

Keyword(s):

Airway Inflammation ◽

Infection Model ◽

Mouse Infection Model ◽

Mouse Infection

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Rapid and quantitative detection of bloodSerratia marcescensby a real-time PCR assay: Its clinical application and evaluation in a mouse infection model

FEMS Microbiology Letters ◽

10.1016/j.femsle.2005.05.041 ◽

2005 ◽

Vol 248 (2) ◽

pp. 163-170 ◽

Cited By ~ 15

Author(s):

Akira Iwaya ◽

Saori Nakagawa ◽

Nobuhiro Iwakura ◽

Ikue Taneike ◽

Mizuki Kurihara ◽

...

Keyword(s):

Real Time ◽

Clinical Application ◽

Real Time Pcr ◽

Quantitative Detection ◽

Infection Model ◽

Pcr Assay ◽

Mouse Infection Model ◽

Mouse Infection

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YersiniaOuter Protein P Inhibits CD8 T Cell Priming in the Mouse Infection Model

The Journal of Immunology ◽

10.4049/jimmunol.174.7.4244 ◽

2005 ◽

Vol 174 (7) ◽

pp. 4244-4251 ◽

Cited By ~ 35

Author(s):

Konrad Trülzsch ◽

Gernot Geginat ◽

Thorsten Sporleder ◽

Klaus Ruckdeschel ◽

Reinhardt Hoffmann ◽

...

Keyword(s):

T Cell ◽

Cd8 T Cell ◽

Infection Model ◽

Mouse Infection Model ◽

Mouse Infection ◽

T Cell Priming

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Bap, a Staphylococcus aureus Surface Protein Involved in Biofilm Formation

Journal of Bacteriology ◽

10.1128/jb.183.9.2888-2896.2001 ◽

2001 ◽

Vol 183 (9) ◽

pp. 2888-2896 ◽

Cited By ~ 468

Author(s):

Carme Cucarella ◽

Cristina Solano ◽

Jaione Valle ◽

Beatriz Amorena ◽

Íñigo Lasa ◽

...

Keyword(s):

Amino Acids ◽

Staphylococcus Aureus ◽

Biofilm Formation ◽

Bovine Mastitis ◽

Surface Protein ◽

Surface Proteins ◽

Infection Model ◽

Mouse Infection Model ◽

New Genes ◽

Inert Surfaces

ABSTRACT Identification of new genes involved in biofilm formation is needed to understand the molecular basis of strain variation and the pathogenic mechanisms implicated in chronic staphylococcal infections. A biofilm-producing Staphylococcus aureus isolate was used to generate biofilm-negative transposon (Tn917) insertion mutants. Two mutants were found with a significant decrease in attachment to inert surfaces (early adherence), intercellular adhesion, and biofilm formation. The transposon was inserted at the same locus in both mutants. This locus (bap [for biofilm associated protein]) encodes a novel cell wall associated protein of 2,276 amino acids (Bap), which shows global organizational similarities to surface proteins of gram-negative (Pseudomonas aeruginosa andSalmonella enterica serovar Typhi) and gram-positive (Enteroccocus faecalis) microorganisms. Bap's core region represents 52% of the protein and consists of 13 successive nearly identical repeats, each containing 86 amino acids. bap was present in a small fraction of bovine mastitis isolates (5% of the 350S. aureus isolates tested), but it was absent from the 75 clinical human S. aureus isolates analyzed. All staphylococcal isolates harboring bap were highly adherent and strong biofilm producers. In a mouse infection modelbap was involved in pathogenesis, causing a persistent infection.

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