Experimental infection of laboratory mice with twoBartonella tribocorumstrains from wildMusspecies: a homologous host-bacteria model system at the genus level

SUMMARYTo date no experimental infection studies have been conducted in laboratory mice usingMusspp. bartonella strains. Therefore we designed a study to evaluate thein vivoinfection characteristics of 2Bartonella tribocorumstrains from wildMusspp. in laboratory mice with the aim of developing a mouse model that reproduces characteristics of naturally acquired bartonella infections in rodents. Groups of outbred CD1 female mice were subcutaneously inoculated with low doses of 2 mouse bartonella strains (10, 100, and 1000 bacteria/mouse). Blood was collected weekly for 27 weeks to evaluate bacteraemia kinetics in infected mice. Mouse urine collected during weeks 3–6 post-inoculation was also tested for viable bacteria to determine whether urine might serve as a source of bacterial transmission. Mice were susceptible to infection with both strains. Bacteraemias in mice lasted up to 25 weeks, sometimes with abacteraemic intervals, and achieved levels up to 107cfu/ml of blood. Temporal lags in bacteraemia onset of up to 19 weeks in length were noted at different inoculum doses. No viable bacteria were detected in mouse urine. Bacteraemic mice displayed characteristics of infection similar to those observed in natural rodent hosts during longitudinal field studies. This mouse model of persistent bacteraemia should be suitable for a variety of experimental uses.

Download Full-text

Identification of key determinants of Staphylococcus aureus vaginal colonization

10.1101/761841 ◽

2019 ◽

Author(s):

Liwen Deng ◽

Katrin Schilcher ◽

Lindsey R. Burcham ◽

Jakub M. Kwiecinski ◽

Paige M. Johsnon ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Mouse Model ◽

Female Reproductive Tract ◽

Transport Systems ◽

Postpartum Women ◽

Post Inoculation ◽

Vaginal Colonization ◽

Fibrinogen Binding ◽

Vaginal Tract

ABSTRACTStaphylococcus aureus is an important pathogen responsible for nosocomial and community acquired infections in humans, and methicillin-resistant S. aureus (MRSA) infections have continued to increase despite wide-spread preventative measures. S. aureus can colonize the female vaginal tract and reports have suggested an increase in MRSA infections in pregnant and postpartum women as well as outbreaks in newborn nurseries. Currently, little is known about specific factors that promote MRSA vaginal colonization and subsequent infection. To study S. aureus colonization of the female reproductive tract in a mammalian system, we developed a mouse model of S. aureus vaginal carriage and demonstrated that both hospital-associated and community-associated MRSA isolates can colonize the murine vaginal tract. Immunohistochemical analysis revealed an increase in neutrophils in the vaginal lumen during MRSA colonization. Additionally, we observed that a mutant lacking fibrinogen binding adhesins exhibited decreased persistence within the mouse vagina. To further identify novel factors that promote vaginal colonization, we performed RNA-sequencing to determine the transcriptome of MRSA growing in vivo during vaginal carriage at 5 hours, 1-day, and 3-days post-inoculation. Over 25% of bacterial genes were differentially regulated at all time points during colonization compared to laboratory cultures. The most highly induced genes were those involved in iron acquisition, including the Isd system and siderophore transport systems. Mutants deficient in these pathways did not persist as well during in vivo colonization. These results reveal that fibrinogen binding as well as the capacity to overcome host nutritional limitation are important determinants of MRSA vaginal colonization.IMPORTANCEStaphylococcus aureus is an opportunistic pathogen able to cause a wide variety of infections in humans. Recent reports have suggested an increasing prevalence of MRSA in pregnant and postpartum women, coinciding with the increased incidence of MRSA infections in the NICU and newborn nurseries. Vertical transmission from mothers to infants at delivery is a likely route of MRSA acquisition by the newborn, however, essentially nothing is known about host and bacterial factors that influence MRSA carriage in the vagina. Here, we established a mouse model of vaginal colonization and observed that multiple MRSA strains can persist in the vaginal tract. Additionally, we determined that MRSA interactions with fibrinogen as well as iron uptake can promote vaginal persistence. This study is the first to identify molecular mechanisms which govern vaginal colonization by MRSA, the critical initial step preceding infection and neonatal transmission.

Download Full-text

Establishment of an Acanthamoeba keratitis mouse model confirmed by amoebic DNA amplification

Scientific Reports ◽

10.1038/s41598-021-83738-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Heekyoung Kang ◽

Hae-Jin Sohn ◽

A-Young Park ◽

A-Jeong Ham ◽

Jeong-Heon Lee ◽

...

Keyword(s):

Mouse Model ◽

Contact Lens ◽

Dna Amplification ◽

Ocular Tissue ◽

In Vivo Model ◽

Rrna Gene ◽

Post Inoculation ◽

Therapeutic Drugs

AbstractAcanthamoeba castellanii, the causative agent of Acanthamoeba keratitis (AK), occurs mainly in contact lens users with poor eye hygiene. The findings of many in vitro studies of AK, as well as the testing of therapeutic drugs, need validation in in vivo experiments. BALB/c mice were used in this study to establish in vivo AK model. A. castellanii cell suspensions (equal mixtures of trophozoites and cysts) were loaded onto 2-mm contact lens pieces and inserted into mouse eyes that were scratched using an ophthalmic surgical blade under anesthesia and the eyelids of the mice were sutured. The AK signs were grossly observed and PCR was performed using P-FLA primers to amplify the Acanthamoeba 18S-rRNA gene from mouse ocular tissue. The experimental AK mouse model was characterized by typical hazy blurring and melting of the mouse cornea established on day 1 post-inoculation. AK was induced with at least 0.3 × 105A. castellanii cells (optimal number, 5 × 104), and the infection persisted for two months. The PCR products amplified from the extracted mouse eye DNA confirmed the development of Acanthamoeba-induced keratitis during the infection periods. In conclusion, the present AK mouse model may serve as an important in vivo model for the development of various therapeutic drugs against AK.

Download Full-text

In Vivo Efficacy of a New Quinolone, DQ-113, against Streptococcus pneumoniae in a Mouse Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.12.3699-3703.2003 ◽

2003 ◽

Vol 47 (12) ◽

pp. 3699-3703 ◽

Cited By ~ 7

Author(s):

Yoshiko Otsu ◽

Katsunori Yanagihara ◽

Yuichi Fukuda ◽

Yoshitsugu Miyazaki ◽

Kazuhiro Tsukamoto ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Mouse Model ◽

Survival Rates ◽

Treated Group ◽

The Other ◽

Time Curve ◽

In Vivo Efficacy ◽

Viable Bacteria ◽

Effective Doses

ABSTRACT DQ-113 is a new quinolone with potent activity against gram-positive pathogens. The in vivo activity of DQ-113 against Streptococcus pneumoniae was compared with those of gatifloxacin and ciprofloxacin in a mouse model. For this purpose, two strains of S. pneumoniae were used: penicillin-susceptible S. pneumoniae (PSSP) and penicillin-resistant S. pneumoniae (PRSP). The survival rates of mice infected with PSSP and PRSP at 14 days after infection were 80% in the DQ-113-treated group and 0 to 10% in the other three groups. In murine infections caused by PSSP, the 50% effective doses (ED50s) of DQ-113, gatifloxacin, and ciprofloxacin were 6.0, 41.3, and 131.6 mg/kg, respectively. Against PRSP-caused pneumonia in mice, the ED50s of DQ-113, gatifloxacin, and ciprofloxacin were 7.6, 64.7, and 125.9 mg/kg, respectively. Compared with the other drugs, DQ-113 showed excellent therapeutic efficacy and eradicated viable bacteria in both PSSP- and PRSP-infected mice. The means ± standard errors of the means of viable bacterium counts in the lungs of gatifloxacin-treated, ciprofloxacin-treated, and untreated control mice infected with PSSP were 2.91 ± 0.34, 3.13 ± 0.48, and 3.86 ± 0.80 log10CFU/ml, respectively. The same counts in mice infected with PRSP treated with the same three agents were 6.57 ± 0.99, 6.54 ± 0.40, and 7.17 ± 0.43 log10 CFU/ml, respectively. DQ-113 significantly decreased the number of viable bacteria in the lungs compared with gatifloxacin and ciprofloxacin. Of the drugs analyzed, the pharmacokinetic-pharmacodynamic parameter of area under the concentration-time curve (AUC)/MIC ratio for DQ-113 was significantly higher than those for gatifloxacin and ciprofloxacin. Our results suggest that DQ-113 has potent in vivo efficacy against both PSSP and PRSP.

Download Full-text