scholarly journals Allele- and Tir-Independent Functions of Intimin in Diverse Animal Infection Models

2012 ◽  
Vol 3 ◽  
Author(s):  
Emily M. Mallick ◽  
Michael J. Brady ◽  
Steven A. Luperchio ◽  
Vijay K. Vanguri ◽  
Loranne Magoun ◽  
...  
Keyword(s):  
Infection Models ◽  
Independent Functions ◽  
Animal Infection

scholarly journals The development of animal infection models and antifungal efficacy assays against clinical isolates ofTrichosporon asahii,T. asteroidesandT. inkin

Virulence ◽  
2015 ◽  
Vol 6 (5) ◽  
pp. 476-486 ◽  
Author(s):  
Marçal Mariné ◽  
Vinicius Leite Pedro Bom ◽  
Patricia Alves de Castro ◽  
Lizziane Kretli Winkelstroter ◽  
Leandra Naira Ramalho ◽  
...  
Keyword(s):  
Clinical Isolates ◽  
Infection Models ◽  
Animal Infection ◽  
Antifungal Efficacy

scholarly journals Identification of Mycobacterium tuberculosis Counterimmune (cim) Mutants in Immunodeficient Mice by Differential Screening

2004 ◽  
Vol 72 (9) ◽  
pp. 5315-5321 ◽  
Author(s):  
Katherine B. Hisert ◽  
Meghan A. Kirksey ◽  
James E. Gomez ◽  
Alexandra O. Sousa ◽  
Jeffery S. Cox ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Genetic Studies ◽  
Immunodeficient Mice ◽  
Immune Mechanisms ◽  
Infection Models ◽  
Animal Infection ◽  
Ifn Γ ◽  
Bacterial Genes ◽  
Oxide Synthase ◽  
Deficient Mice

ABSTRACT Tuberculosis (TB) is characterized by lifetime persistence of Mycobacterium tuberculosis. Despite the induction of a vigorous host immune response that curtails disease progression in the majority of cases, the organism is not eliminated. Subsequent immunosuppression can lead to reactivation after a prolonged period of clinical latency. Thus, while it is clear that protective immune mechanisms are engaged during M. tuberculosis infection, it also appears that the pathogen has evolved effective countermechanisms. Genetic studies with animal infection models and with patients have revealed a key role for the cytokine gamma interferon (IFN-γ) in resistance to TB. IFN-γ activates a large number of antimicrobial pathways. Three of these IFN-γ-dependent mechanisms have been implicated in defense against M. tuberculosis: inducible nitric oxide synthase (iNOS), phagosome oxidase (phox), and the phagosome-associated GTPase LRG-47. In order to identify bacterial genes that provide protection against specific host immune pathways, we have developed the strategy of differential signature-tagged transposon mutagenesis. Using this approach we have identified three M. tuberculosis genes that are essential for progressive M. tuberculosis growth and rapid lethality in iNOS-deficient mice but not in IFN-γ-deficient mice. We propose that these genes are involved in pathways that allow M. tuberculosis to counter IFN-γ-dependent immune mechanisms other than iNOS.

scholarly journals In Vivo Activity of Oritavancin in Animal Infection Models and Rationale for a New Dosing Regimen in Humans

2012 ◽  
Vol 54 (suppl 3) ◽  
pp. S220-S228 ◽  
Author(s):  
P. G. Ambrose ◽  
G. L. Drusano ◽  
W. A. Craig
Keyword(s):  
Dosing Regimen ◽  
Infection Models ◽  
Animal Infection

scholarly journals Use of anInVitroPharmacodynamic Model To Derive a Moxifloxacin Regimen That Optimizes Kill ofYersinia pestisand Prevents Emergence of Resistance

2010 ◽  
Vol 55 (2) ◽  
pp. 822-830 ◽  
Author(s):  
A. Louie ◽  
H. S. Heine ◽  
B. VanScoy ◽  
A. Eichas ◽  
K. Files ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Dose Range ◽  
Human Infection ◽  
Pharmacodynamic Model ◽  
Dose Fractionation ◽  
Time Curve ◽  
Infection Models ◽  
Animal Infection ◽  
Emergence Of Resistance

ABSTRACTYersinia pestis, the causative agent of bubonic, septicemic, and pneumonic plague, is classified as a CDC category A bioterrorism pathogen. Streptomycin and doxycycline are the “gold standards” for the treatment of plague. However, streptomycin is not available in many countries, andY. pestisisolates resistant to streptomycin and doxycycline occur naturally and have been generated in laboratories. Moxifloxacin is a fluoroquinolone antibiotic that demonstrates potent activity againstY. pestisinin vitroand animal infection models. However, the dose and frequency of administration of moxifloxacin that would be predicted to optimize treatment efficacy in humans while preventing the emergence of resistance are unknown. Therefore, dose range and dose fractionation studies for moxifloxacin were conducted forY. pestisin anin vitropharmacodynamic model in which the half-lives of moxifloxacin in human serum were simulated so as to identify the lowest drug exposure and the schedule of administration that are linked with killing ofY. pestisand with the suppression of resistance. In the dose range studies, simulated moxifloxacin regimens of ≥175 mg/day killed drug-susceptible bacteria without resistance amplification. Dose fractionation studies demonstrated that the AUC (area under the concentration-time curve)/MIC ratio predicted kill of drug-susceptibleY. pestis, while theCmax(maximum concentration of the drug in serum)/MIC ratio was linked to resistance prevention. Monte Carlo simulations predicted that moxifloxacin at 400 mg/day would successfully treat human infection due toY. pestisin 99.8% of subjects and would prevent resistance amplification. We conclude that in anin vitropharmacodynamic model, the clinically prescribed moxifloxacin regimen of 400 mg/day is predicted to be highly effective for the treatment ofY. pestisinfections in humans. Studies of moxifloxacin in animal models of plague are warranted.

scholarly journals Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic HumanEx VivoInfection Model

2015 ◽  
Vol 84 (3) ◽  
pp. 711-722 ◽  
Author(s):  
Marko Weidensdorfer ◽  
Ju Ik Chae ◽  
Celestine Makobe ◽  
Julia Stahl ◽  
Beate Averhoff ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Pathogenic Bacteria ◽  
Ex Vivo ◽  
Bartonella Henselae ◽  
Dependent Manner ◽  
Content Type ◽  
Human Pathogenic Bacteria ◽  
Infection Models ◽  
Animal Infection

Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However,in vitroinfections of cell monolayers reflect thein vivosituation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore,ex vivoinfection of human organs might represent an attractive method to overcome these limitations. We infected whole human umbilical cordsex vivowithBartonella henselaeorAcinetobacter baumanniiunder dynamic flow conditions mimicking thein vivoinfection situation of human endothelium. For this purpose, methods for quantifying endothelium-adherent wild-type and trimeric autotransporter adhesin (TAA)-deficient bacteria were set up. Data revealed that (i)A. baumanniibinds in a TAA-dependent manner to endothelial cells, (ii) this organ infection model led to highly reproducible adherence rates, and furthermore, (iii) this model allowed to dissect the biological function of TAAs in the natural course of human infections. These findings indicate that infection models usingex vivohuman tissue samples (“organ microbiology”) might be a valuable tool in analyzing bacterial pathogenicity with the capacity to replace animal infection models at least partially.

scholarly journals RssAB-FlhDC-ShlBA as a Major Pathogenesis Pathway in Serratia marcescens

2010 ◽  
Vol 78 (11) ◽  
pp. 4870-4881 ◽  
Author(s):  
Chuan-Sheng Lin ◽  
Jim-Tong Horng ◽  
Chun-Hung Yang ◽  
Yu-Huan Tsai ◽  
Lin-Hui Su ◽  
...  
Keyword(s):  
Serratia Marcescens ◽  
Biofilm Formation ◽  
Inflammatory Responses ◽  
Systemic Infection ◽  
Opportunistic Pathogen ◽  
Positive Control ◽  
Regulatory Pathway ◽  
Two Component System ◽  
Infection Models ◽  
Animal Infection

ABSTRACT Serratia marcescens has long been recognized as an important opportunistic pathogen, but the underlying pathogenesis mechanism is not completely clear. Here, we report a key pathogenesis pathway in S. marcescens comprising the RssAB two-component system and its downstream elements, FlhDC and the dominant virulence factor hemolysin ShlBA. Expression of shlBA is under the positive control of FlhDC, which is repressed by RssAB signaling. At 37°C, functional RssAB inhibits swarming, represses hemolysin production, and promotes S. marcescens biofilm formation. In comparison, when rssBA is deleted, S. marcescens displays aberrant multicellularity favoring motile swarming with unbridled hemolysin production. Cellular and animal infection models further demonstrate that loss of rssBA transforms this opportunistic pathogen into hypervirulent phenotypes, leading to extensive inflammatory responses coupled with destructive and systemic infection. Hemolysin production is essential in this context. Collectively, a major virulence regulatory pathway is identified in S. marcescens.

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