Complement Depletion Renders C57BL/6 Mice Sensitive to the
            <i>Bacillus anthracis</i>
            Sterne Strain

Harvill, Eric T.; Lee, Gloria; Grippe, Vanessa K.; Merkel, Tod J.

doi:10.1128/iai.73.7.4420-4422.2005

Cited by 43 publications

(44 citation statements)

References 12 publications

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“…Although the B. anthracis Sterne strain is attenuated in many mammalian species, certain strains of inbred mice, including DBA/2J, are susceptible to this bacterium, making this strain an excellent model system for virulence studies (12,35). We used intratracheal injection of spores into the lungs as a model for inhalational anthrax (10).…”

Section: Resultsmentioning

confidence: 99%

The Germination-Specific Lytic Enzymes SleB, CwlJ1, and CwlJ2 Each Contribute to Bacillus anthracis Spore Germination and Virulence

et al. 2009

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The bacterial spore cortex is critical for spore stability and dormancy and must be hydrolyzed by germination-specific lytic enzymes (GSLEs), which allows complete germination and vegetative cell outgrowth. We created in-frame deletions of three genes that encode GSLEs that have been shown to be active in Bacillus anthracis germination: sleB, cwlJ1, and cwlJ2. Phenotypic analysis of individual null mutations showed that the removal of any one of these genes was not sufficient to disrupt spore germination in nutrient-rich media. This finding indicates that these genes have partially redundant functions. Double and triple deletions of these genes resulted in more significant defects. Although a small subset of ⌬sleB ⌬cwlJ1 spores germinate with wild-type kinetics, for the overall population there is a 3-order-of-magnitude decrease in the colony-forming efficiency compared with wild-type spores. ⌬sleB ⌬cwlJ1 ⌬cwlJ2 spores are unable to complete germination in nutrient-rich conditions in vitro. Both ⌬sleB ⌬cwlJ1 and ⌬sleB ⌬cwlJ1 ⌬cwlJ2 spores are significantly attenuated, but are not completely devoid of virulence, in a mouse model of inhalation anthrax. Although unable to germinate in standard nutrient-rich media, spores lacking SleB, CwlJ1, and CwlJ2 are able to germinate in whole blood and serum in vitro, which may explain the persistent low levels of virulence observed in mouse infections. This work contributes to our understanding of GSLE activation and function during germination. This information may result in identification of useful therapeutic targets for the disease anthrax, as well as provide insights into ways to induce the breakdown of the protective cortex layer, facilitating easier decontamination of resistant spores.

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Section: Resultsmentioning

confidence: 99%

The Germination-Specific Lytic Enzymes SleB, CwlJ1, and CwlJ2 Each Contribute to Bacillus anthracis Spore Germination and Virulence

et al. 2009

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“…173 As a whole, strains with the Hc 0 mutation are more susceptible to infection with Bacillus anthracis, Aspergillus fumigatus, and Candida albicans compared with the C57BL/6 strain, which has intact C5. 56,114,132,152,163 However, strains with Hc 0 are associated with lower susceptibility to cerebral malaria after infection with Plasmodium berghei, as a result of reduced C5a-induced cytokine expression. 126 C5 has also been shown to play a role in the development of immune-mediated diseases in mice.…”

Section: Immune Variation Among Inbred Mouse Strains: Selected Examplesmentioning

confidence: 99%

Immunological Variation Between Inbred Laboratory Mouse Strains

et al. 2011

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Inbred laboratory mouse strains are highly divergent in their immune response patterns as a result of genetic mutations and polymorphisms. The generation of genetically engineered mice (GEM) has, in the past, used embryonic stem (ES) cells for gene targeting from various 129 substrains followed by backcrossing into more fecund mouse strains. Although common inbred mice are considered ''immune competent,'' many have variations in their immune system-some of which have been described-that may affect the phenotype. Recognition of these immune variations among commonly used inbred mouse strains is essential for the accurate interpretation of expected phenotypes or those that may arise unexpectedly. In GEM developed to study specific components of the immune system, accurate evaluation of immune responses must take into consideration not only the gene of interest but also how the background strain and microbial milieu contribute to the manifestation of findings in these mice. This article discusses points to consider regarding immunological differences between the common inbred laboratory mouse strains, particularly in their use as background strains in GEM.

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“…Thus we compared the induction of cell death and IL-1b protein secretion in murine macrophages from 129S mice, known to be sensitive to anthrax LT, to murine macrophages from C57BL/6 and A/J mice, which are known to be resistant to LT [21]. A/J mice were included because this strain of mouse is more susceptible to lethal infection with BA than other strains [25,26].…”

Section: Ba Spores and Lt Induce Il-1b By Distinct Signaling Pathwaysmentioning

confidence: 99%

Bacillus anthracis spores and lethal toxin induce IL‐1β via functionally distinct signaling pathways

et al. 2008

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Previous reports suggested that lethal toxin (LT)-induced caspase-1 activity and/or IL-1b accounted for Bacillus anthracis (BA) infection lethality. In contrast, we now report that caspase-1-mediated IL-1b expression in response to BA spores is required for anti-BA host defenses. Caspase-1 -/-and IL-1b -/-mice are more susceptible than wild-type (WT) mice to lethal BA infection, are less able to kill BA both in vivo and in vitro, and addition of rIL-1b to macrophages from these mice restored killing in vitro. Non-germinating BA spores induced caspase-1 activity, IL-1b and nitric oxide, by which BA are killed in WT but not in caspase-1 -/-mice, suggesting that the spore itself stimulated inflammatory responses.While spores induced IL-1b in LT-susceptible and -resistant macrophages, LT induced IL-1b only in LT-susceptible macrophages. Cooperation between MyD88-dependent and -independent signaling pathways was required for spore-induced, but not LT-induced, IL-1b. While both spores and LT induced caspase-1 activity and IL-1b, LT did not induce IL-1b mRNA, and spores did not induce cell death. Thus different components of the same bacterium each induce IL-1b by distinct signaling pathways. Whereas the spore-induced IL-1b limits BA infection, LT-induced IL-1b enables BA to escape host defenses.

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Complement Depletion Renders C57BL/6 Mice Sensitive to the Bacillus anthracis Sterne Strain

Cited by 43 publications

References 12 publications

The Germination-Specific Lytic Enzymes SleB, CwlJ1, and CwlJ2 Each Contribute to Bacillus anthracis Spore Germination and Virulence

The Germination-Specific Lytic Enzymes SleB, CwlJ1, and CwlJ2 Each Contribute to Bacillus anthracis Spore Germination and Virulence

Immunological Variation Between Inbred Laboratory Mouse Strains

Bacillus anthracis spores and lethal toxin induce IL‐1β via functionally distinct signaling pathways

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