Animal Models for<i>Francisella tularensis</i>and<i>Burkholderia</i>Species

Stundick, M. V.; Albrecht, Mark T.; Houchens, Christopher R.; Smith, Alyssa; Dreier, Thomas M.; Larsen, Joseph

doi:10.1177/0300985813486812

Cited by 17 publications

(10 citation statements)

References 109 publications

(123 reference statements)

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“…BALB/c and C57BL/6 mice and guinea pigs are highly susceptible hosts to F. tularensis infection, but also to the LVS strain of F. tularensis subsp. holarctica and F. novicida strains, which have often been used as surrogates of F. tularensis , although they are much less virulent in humans (Stundick et al, 2013; Kingry and Petersen, 2014). Rabbits and Fisher 344 rats are less susceptible to F. tularensis infection and may better mimic human infection.…”

Section: Animal Modelsmentioning

confidence: 99%

“…However, variable immune responses to F. tularensis infection also exist between rat strains, with Sprague-Dawley being much more resistant than Fisher 344 rats (Raymond and Conlan, 2009). Results may also vary according to the route of infection, i.e., the intraperitoneal, intradermal, subcutaneous or intranasal routes for Fischer 344 rats (Stundick et al, 2013). Moreover, the “Animal Rule” states that experimental animal models should be developed using the true etiologic agent causing human disease.…”

Section: Animal Modelsmentioning

confidence: 99%

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Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

Caspar

Maurin

2017

Front. Cell. Infect. Microbiol.

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The antibiotic classes that are recommended for tularaemia treatment are the aminoglycosides, the fluoroquinolones and the tetracyclines. However, cure rates vary between 60 and 100% depending on the antibiotic used, the time to appropriate antibiotic therapy setup and its duration, and the presence of complications, such as lymph node suppuration. Thus, antibiotic susceptibility testing (AST) of F. tularensis strains remains of primary importance for detection of the emergence of antibiotic resistances to first-line drugs, and to test new therapeutic alternatives. However, the AST methods reported in the literature were poorly standardized between studies and AST data have not been previously evaluated in a comprehensive and comparative way. The aim of the present review was to summarize experimental data on antibiotic susceptibilities of F. tularensis obtained in acellular media, cell models and animal models since the introduction of fluoroquinolones in the treatment of tularaemia in 1989. We compiled MIC data of 33 antibiotics (including aminoglycosides, fluoroquinolones, tetracyclines, macrolides, β-lactams, chloramphenicol, rifampicin, and linezolid) against 900 F. tularensis strains (504 human strains), including 107 subsp. tularensis (type A), 789 subsp. holarctica (type B) and four subsp. mediasiatica strains, using various AST methods. Specific culture media were identified or confirmed as unsuitable for AST of F. tularensis. Overall, MICs were the lowest for ciprofloxacin (≤ 0.002–0.125 mg/L) and levofloxacin, and ranged from ≤ 0.016 to 2 mg/L for gentamicin, and 0.064 to 4 mg/L for doxycycline. No resistant strain to any of these antibiotics was reported. Fluoroquinolones also exhibited a bactericidal activity against intracellular F. tularensis and lower relapse rates in animal models when compared with the bacteriostatic compound doxycycline. As expected, lower MIC values were found for macrolides against type A and biovar I type B strains, compared to biovar II type B strains. The macrolides were more effective against F. tularensis grown in phagocytic cells than in acellular media.

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Section: Animal Modelsmentioning

confidence: 99%

Section: Animal Modelsmentioning

confidence: 99%

Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

Caspar

Maurin

2017

Front. Cell. Infect. Microbiol.

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“…Although studies in literature indicate that the NHP model resembles tularemia disease in humans better than other models, published data lacks critical findings regarding well-characterized animal models for Animal Rule applications, such as clinical signs, clinical pathology, and gross and microscopic pathology [7]. …”

Section: Introductionmentioning

confidence: 99%

Comparison of experimental respiratory tularemia in three nonhuman primate species

Glynn

Alves

Frick

et al. 2015

Comparative Immunology, Microbiology and Infectious Diseases

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Tularemia is a zoonotic disease caused by Francisella tularensis, which is transmitted to humans most commonly by contact with infected animals, tick bites, or inhalation of aerosolized bacteria. F. tularensis is highly infectious via the aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic tularemia. Left untreated, the pneumonic form has more than > 30% case-fatality rate but with early antibiotic intervention can be reduced to 3%. This study compared tularemia disease progression across three species of nonhuman primates [African green monkey (AGM), cynomolgus macaque (CM), and rhesus macaque (RM)] following aerosolized F. tularensis Schu S4 exposure. Groups of the animals exposed to various challenge doses were observed for clinical signs of infection and blood samples were analyzed to characterize the disease pathogenesis. Whereas the AGMs and CMs succumbed to disease following challenge doses of 40 and 32 colony forming units (CFU), respectively, the RM lethal dose was 276,667 CFU. Following all challenge doses that caused disease, the NHPs experienced weight loss, bacteremia, fever as early as 4 days post exposure, and tissue burden. Necrotizing-to-pyogranulomatous lesions were observed most commonly in the lung, lymph nodes, spleen, and bone marrow. Overall, the CM model consistently manifested pathological responses similar to those resulting from inhalation of F. tularensis in humans and thereby most closely emulates human tularemia disease. The RM model displayed a higher tolerance to infection and survived exposures of up to 15,593 CFU of aerosolized F. tularensis.

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“…On the other hand, respiratory pathogens like Burkholderia pseudomallei has the same type of tropism in mice than that observed in humans, regardless of its acute or chronic output ( Stundick et al, 2013 ). Modeling of experimental melioidosis has been conducted in numerous biologically relevant models including mammalian and invertebrate hosts (reviewed in Warawa, 2010 ).…”

Section: From Classic To Alternative Models In Studying Relevant Bactmentioning

confidence: 99%

Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

Hernández¹,

Yero

Pinos-Rodríguez

et al. 2015

Front. Microbiol.

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Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions.

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Animal Models forFrancisella tularensisandBurkholderiaSpecies

Cited by 17 publications

References 109 publications

Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

Comparison of experimental respiratory tularemia in three nonhuman primate species

Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

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