scholarly journals Chlamydial Variants Differ in Ability To Ascend the Genital Tract in the Guinea Pig Model of Chlamydial Genital Infection

2015 ◽  
Vol 83 (8) ◽  
pp. 3176-3183 ◽  
Author(s):  
Laxmi Yeruva ◽  
Anne K. Bowlin ◽  
Nicole Spencer ◽  
Anthony T. Maurelli ◽  
Roger G. Rank
Keyword(s):  
Guinea Pig ◽  
Genital Tract ◽  
Animal Studies ◽  
Reproductive Hormones ◽  
Physiological Effects ◽  
Content Type ◽  
Lower Genital Tract ◽  
Tract Disease ◽  
Repeated Infections ◽  
Guinea Pig Model

An important question in the study of chlamydial genital tract disease is why some women develop severe upper tract disease while others have mild or even “silent” infections with or without pathology. Animal studies suggest that the pathological outcome of an infection is dependent upon both the composition of the infecting chlamydial population and the genotype of the host, along with host physiological effects, such as the cyclical production of reproductive hormones and even the size of the infecting inoculum or the number of repeated infections. In this study, we compared two variants ofChlamydia caviae, contrasting in virulence, with respect to their abilities to ascend the guinea pig genital tract. We then determined the effect of combining the two variants on the course of infection and on the bacterial loads of the two variants in the genital tract. Although the variants individually had similar infection kinetics in the cervix, SP6, the virulent variant, could be isolated from the oviducts more often and in greater numbers than the attenuated variant, AZ2. SP6 also elicited higher levels of interleukin 8 (IL-8) in the lower genital tract and increased leukocyte infiltration in the cervix and uterus compared to AZ2. When the two variants were combined in a mixed infection, SP6 outcompeted AZ2 in the lower genital tract; however, AZ2 was able to ascend the genital tract as readily as SP6. These data suggest that the ability of SP6 to elicit an inflammatory response in the lower genital tract facilitates the spread of both variants to the oviducts.

A novel guinea pig model of Chlamydia trachomatis genital tract infection

Vaccine ◽  
2011 ◽  
Vol 29 (35) ◽  
pp. 5994-6001 ◽  
Author(s):  
Marien I. de Jonge ◽  
Sander A.S. Keizer ◽  
Hicham M. el Moussaoui ◽  
Lieke van Dorsten ◽  
Rima Azzawi ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Tract Infection ◽  
Guinea Pig ◽  
Genital Tract ◽  
Pig Model ◽  
Genital Tract Infection ◽  
Guinea Pig Model

scholarly journals Key Role of Capsular Polysaccharide in the Induction of Systemic Infection and Abortion by Hypervirulent Campylobacter jejuni

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orhan Sahin ◽  
Samantha A. Terhorst ◽  
Eric R. Burrough ◽  
Zhangqi Shen ◽  
Zuowei Wu ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Campylobacter Jejuni ◽  
Capsular Polysaccharide ◽  
Systemic Infection ◽  
The United States ◽  
Content Type ◽  
Model Following ◽  
Capsule Production ◽  
Guinea Pig Model

ABSTRACT Campylobacter jejuni is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested Campylobacter must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. C. jejuni is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared with C. jejuni NCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulent C. jejuni.

scholarly journals The Chlamydia-Secreted Protease CPAF Promotes Chlamydial Survival in the Mouse Lower Genital Tract

2016 ◽  
Vol 84 (9) ◽  
pp. 2697-2702 ◽  
Author(s):  
Zhangsheng Yang ◽  
Lingli Tang ◽  
Lili Shao ◽  
Yuyang Zhang ◽  
Tianyuan Zhang ◽  
...  
Keyword(s):  
Genital Tract ◽  
Chlamydial Infection ◽  
Critical Role ◽  
Content Type ◽  
Lower Genital Tract ◽  
Successful Infection ◽  
Multiple Strains

Despite the extensivein vitrocharacterization of CPAF (chlamydialprotease/proteasome-likeactivityfactor), its role in chlamydial infection and pathogenesis remains unclear. We now report that aChlamydia trachomatisstrain deficient in expression of CPAF (L2-17) is no longer able to establish a successful infection in the mouse lower genital tract following an intravaginal inoculation. The L2-17 organisms were cleared from the mouse lower genital tract within a few days, while a CPAF-sufficientC. trachomatisstrain (L2-5) survived in the lower genital tract for more than 3 weeks. However, both the L2-17 and L2-5 organisms maintained robust infection courses that lasted up to 4 weeks when they were directly delivered into the mouse upper genital tract. The CPAF-dependent chlamydial survival in the lower genital tract was confirmed in multiple strains of mice. Thus, we have demonstrated a critical role of CPAF in promotingC. trachomatissurvival in the mouse lower genital tracts. It will be interesting to further investigate the mechanisms of the CPAF-dependent chlamydial pathogenicity.

Recognition of Official Sponsors of the Journal of the Lower Genital Tract Disease

2005 ◽  
Vol 9 (4) ◽  
pp. 205
Author(s):  
Edward J Wilkinson ◽  
L Stewart Massad ◽  
Alan G Waxman ◽  
Thomas M Julian
Keyword(s):  
Genital Tract ◽  
Lower Genital Tract ◽  
Tract Disease

scholarly journals Efficacy of the Investigational Echinocandin ASP9726 in a Guinea Pig Model of Invasive Pulmonary Aspergillosis

2015 ◽  
Vol 59 (5) ◽  
pp. 2875-2881 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Satoru Matsumoto ◽  
Rosie A. Bocanegra ◽  
Monica L. Herrera ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Quantitative Pcr ◽  
Guinea Pigs ◽  
Plasma Concentrations ◽  
Invasive Pulmonary Aspergillosis ◽  
Pig Model ◽  
Pulmonary Aspergillosis ◽  
Content Type ◽  
Fungal Burden ◽  
Guinea Pig Model

ABSTRACTASP9726 is an investigational echinocandin within vitroactivity againstAspergillusspecies. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated withA. fumigatusAF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1→3)-β-d-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1→3)-β-d-glucan and galactomannan levels, but only voriconazole significantly reduced numbers of CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology demonstrated morphological changes in hyphae in animals exposed to ASP9726 and caspofungin, consistent with the activities of the echinocandins. These results suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary aspergillosis.

scholarly journals Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Hwan Keun Kim ◽  
Fabiana Falugi ◽  
Lena Thomer ◽  
Dominique M. Missiakas ◽  
Olaf Schneewind
Keyword(s):  
Staphylococcus Aureus ◽  
Guinea Pig ◽  
B Cell ◽  
Bloodstream Infection ◽  
Guinea Pigs ◽  
Protective Immunity ◽  
Protein A ◽  
Pig Model ◽  
Content Type ◽  
Guinea Pig Model

ABSTRACT  Staphylococcus aureusinfection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.IMPORTANCE Staphylococcus aureusis the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines.

scholarly journals Evaluation of the Efficacy of ME1111 in the Topical Treatment of Dermatophytosis in a Guinea Pig Model

2016 ◽  
Vol 60 (4) ◽  
pp. 2343-2345 ◽  
Author(s):  
L. Long ◽  
C. Hager ◽  
M. Ghannoum
Keyword(s):  
Guinea Pig ◽  
Topical Treatment ◽  
Liver Toxicity ◽  
Trichophyton Mentagrophytes ◽  
Pig Model ◽  
Once Daily ◽  
Content Type ◽  
The Past ◽  
Guinea Pig Model

ABSTRACTThe treatment of dermatophytoses, including onychomycosis, has come a long way over the past few decades with the introduction of oral antifungals (e.g., terbinafine and itraconazole). However, with these advancements in oral therapies come several undesirable effects, such as kidney and liver toxicity, along with drug-drug interactions. Consequently, there is a need for new topical agents that are effective against dermatophytosis. ME1111 is a topical antifungal under development. In this study, thein vivoefficacy of ME1111 was compared to that of ciclopirox in the topical treatment of dermatophytosis caused byTrichophyton mentagrophytesusing a guinea pig model. Animals were treated with the topical antifungals starting at 3 days postinfection, with each agent being applied once daily for seven consecutive days. After the treatment period, the clinical and mycological efficacies were evaluated. The data showed that both antifungals demonstrated significant clinical and mycological efficacies; however, ME1111 showed clinical efficacy superior to that of ciclopirox (46.9% and 25.0%, respectively, with aPvalue of <0.001). The potent efficacy of ME1111 could be attributed to its properties, such as low keratin binding.

scholarly journals Rifapentine Is Not More Active than Rifampin against Chronic Tuberculosis in Guinea Pigs

2012 ◽  
Vol 56 (7) ◽  
pp. 3726-3731 ◽  
Author(s):  
Noton K. Dutta ◽  
Peter B. Illei ◽  
Charles A. Peloquin ◽  
Michael L. Pinn ◽  
Khisimuzi E. Mdluli ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Current Treatment ◽  
Active Tuberculosis ◽  
Pig Model ◽  
Intracellular Accumulation ◽  
Duration Of Treatment ◽  
Content Type ◽  
Guinea Pig Model ◽  
Culture Positive

ABSTRACTRifamycins are key sterilizing drugs in the current treatment of active tuberculosis (TB). Daily dosing of rifapentine (P), a potent rifamycin with high intracellular accumulation, in place of rifampin (R) in the standard antitubercular regimen significantly shortens the duration of treatment needed to prevent relapse in a murine model of active TB. We undertook the current study to compare directly the activities of human-equivalent doses of P and R in a guinea pig model of chronic TB, in which bacilli are predominantly extracellular within human-like necrotic granulomas. Hartley strain guinea pigs were aerosol infected with ∼200 bacilli ofMycobacterium tuberculosisH37Rv, and treatment given 5 days/week was initiated 6 weeks later. R at 100 mg/kg of body weight and P at 100 mg/kg were given orally alone or in combination with isoniazid (H) at 60 mg/kg and pyrazinamide (Z) at 300 mg/kg. Culture-positive relapse was assessed in subgroups of guinea pigs after completion of 1 and 2 months of treatment. Human-equivalent doses of R and P showed equivalent bactericidal activity when used alone and in combination therapy. In guinea pigs treated with rifampin, isoniazid, and pyrazinamide (RHZ) or PHZ, microbiological relapse occurred in the lungs of 8/10 animals treated for 1 month and in 0/10 animals treated for 2 months. Substitution of P for R in the standard antitubercular regimen did not shorten the time to cure in this guinea pig model of chronic TB. Data from ongoing clinical trials comparing the activity of these two drugs are awaited to determine the relevance of the guinea pig TB model in preclinical drug screening.

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