Galleria mellonella as an Infection Model for Bacillus anthracis Sterne

Malmquist, Jacob A.; Rogan, Madison R.; McGillivray, Shauna M.

doi:10.3389/fcimb.2019.00360

Cited by 12 publications

(9 citation statements)

References 31 publications

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“…mellonella infection model suitable for our inferences because it has been used to characterize major B . anthracis Sterne virulence factors following vegetative cell challenge [ 69 ] and for down-selecting antibacterial peptides active against Ba for future use in an animal model [ 70 ]. It also allows challenge of desired animal numbers inexpensively and humanely while serving as an accurate innate immune animal model.…”

Section: Resultsmentioning

confidence: 99%

Convergent evolution of diverse Bacillus anthracis outbreak strains toward altered surface oligosaccharides that modulate anthrax pathogenesis

et al. 2020

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Bacillus anthracis, a spore-forming gram-positive bacterium, causes anthrax. The external surface of the exosporium is coated with glycosylated proteins. The sugar additions are capped with the unique monosaccharide anthrose. The West African Group (WAG) B. anthracis have mutations rendering them anthrose deficient. Through genome sequencing, we identified 2 different large chromosomal deletions within the anthrose biosynthetic operon of B. anthracis strains from Chile and Poland. In silico analysis identified an anthrose-deficient strain in the anthrax outbreak among European heroin users. Anthrose-deficient strains are no longer restricted to West Africa so the role of anthrose in physiology and pathogenesis was investigated in B. anthracis Sterne. Loss of anthrose delayed spore germination and enhanced sporulation. Spores without anthrose were phagocytized at higher rates than spores with anthrose, indicating that anthrose may serve an antiphagocytic function on the spore surface. The anthrose mutant had half the LD50 and decreased time to death (TTD) of wild type and complement B. anthracis Sterne in the A/J mouse model. Following infection, anthrose mutant bacteria were more abundant in the spleen, indicating enhanced dissemination of Sterne anthrose mutant. At low sample sizes in the A/J mouse model, the mortality of ΔantC-infected mice challenged by intranasal or subcutaneous routes was 20% greater than wild type. Competitive index (CI) studies indicated that spores without anthrose disseminated to organs more extensively than a complemented mutant. Death process modeling using mouse mortality dynamics suggested that larger sample sizes would lead to significantly higher deaths in anthrose-negative infected animals. The model was tested by infecting Galleria mellonella with spores and confirmed the anthrose mutant was significantly more lethal. Vaccination studies in the A/J mouse model showed that the human vaccine protected against high-dose challenges of the nonencapsulated Sterne-based anthrose mutant. This work begins to identify the physiologic and pathogenic consequences of convergent anthrose mutations in B. anthracis.

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Section: Resultsmentioning

confidence: 99%

Convergent evolution of diverse Bacillus anthracis outbreak strains toward altered surface oligosaccharides that modulate anthrax pathogenesis

et al. 2020

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“…ClpX is essential for virulence in B. anthracis , even in the fully virulent, encapsulated strain ( McGillivray et al, 2009 ). To determine the role of the ClpP subunits in virulence, we used the caterpillar larvae of G. mellonella , an invertebrate infection model that shares many similarities to the mammalian innate immune system and that has been previously shown to be a reliable animal model for B. anthracis Sterne ( Malmquist et al, 2019 ). We compared G. mellonella survival after injection with either PBS or the B. anthracis Sterne strains ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

Loss of the ClpXP Protease Leads to Decreased Resistance to Cell-Envelope Targeting Antimicrobials in Bacillus anthracis Sterne

et al. 2021

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The ClpX ATPase is critical for resistance to cell envelope targeting antibiotics in Bacillus anthracis, however, it is unclear whether this is due to its function as an independent chaperone or as part of the ClpXP protease. In this study, we demonstrate that antibiotic resistance is due to formation of the ClpXP protease through construction of a ClpX complementation plasmid that is unable to interact with ClpP. Additionally, we genetically disrupted both clpP genes, clpP1 and clpP2, found in B. anthracis Sterne and find that the loss of either increases susceptibility to cell envelope targeting antimicrobials, although neither has as strong of a phenotype as loss of clpX and neither clpP gene is essential for virulence in a G. mellonella model of infection. Lastly, we looked at changes to cell envelope morphology that could contribute to increased antibiotic sensitivity. We find no difference in cell charge or cell lysis, although we do see increased hydrophobicity in the ΔclpX strain, decreased cellular density and slightly thinner cells walls. We also see significant cell division defects in ΔclpX, although only when cells are grown in the mammalian cell culture medium, RPMI. We conclude that the intrinsic resistance of B. anthracis to cell wall active antimicrobials is dependent on formation of the ClpXP protease and that this could be due, at least in part, to the role of ClpX in regulating cell envelope morphology.

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“… 2019 ; Hardy et al . 2019 ; Malmquist, Rogan and McGillivray 2019 ; Marcos-Zambrano et al . 2020 ; Vilela et al .…”

Section: G Mellonella As An Insect Model Organism For Immunmentioning

confidence: 99%

The greater wax mothGalleria mellonella: biology and use in immune studies

Wojda

Staniec

Sułek

et al. 2020

Pathogens and Disease

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The greater wax moth Galleria mellonella is an invertebrate, which is increasingly being used in scientific research. Its ease of reproduction, numerous offspring, short development cycle, and, finally, its known genome and immune-related transcriptome provide a convenient research model for investigation of insect immunity at the biochemical and molecular levels. Galleria immunity, consisting of only innate mechanisms, shows adaptive plasticity, which has recently become the subject of intensive scientific research. This insect serves as a mini host in studies of the pathogenicity of microorganisms and in vivo tests of the effectiveness of single virulence factors as well as new antimicrobial compounds. Certainly, the Galleria mellonella species deserves our attention and appreciation for its contribution to the development of research on innate immune mechanisms. In this review article, we describe the biology of the greater wax moth, summarize the main advantages of using it as a model organism, and present some main techniques facilitating work with this animal.

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Galleria mellonella as an Infection Model for Bacillus anthracis Sterne

Cited by 12 publications

References 31 publications

Convergent evolution of diverse Bacillus anthracis outbreak strains toward altered surface oligosaccharides that modulate anthrax pathogenesis

Convergent evolution of diverse Bacillus anthracis outbreak strains toward altered surface oligosaccharides that modulate anthrax pathogenesis

Loss of the ClpXP Protease Leads to Decreased Resistance to Cell-Envelope Targeting Antimicrobials in Bacillus anthracis Sterne

The greater wax mothGalleria mellonella: biology and use in immune studies

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