8 research outputs found
Conidiation Color Mutants of Aspergillus fumigatus Are Highly Pathogenic to the Heterologous Insect Host Galleria mellonella
The greater wax moth Galleria mellonella has been widely used as
a heterologous host for a number of fungal pathogens including Candida
albicans and Cryptococcus neoformans. A positive
correlation in pathogenicity of these yeasts in this insect model and animal
models has been observed. However, very few studies have evaluated the
possibility of applying this heterologous insect model to investigate virulence
traits of the filamentous fungal pathogen Aspergillus
fumigatus, the leading cause of invasive aspergillosis. Here, we have
examined the impact of mutations in genes involved in melanin biosynthesis on
the pathogenicity of A. fumigatus in the G.
mellonella model. Melanization in A. fumigatus confers
bluish-grey color to conidia and is a known virulence factor in mammal models.
Surprisingly, conidial color mutants in B5233 background that have deletions in
the defined six-gene cluster required for DHN-melanin biosynthesis caused
enhanced insect mortality compared to the parent strain. To further examine and
confirm the relationship between melanization defects and enhanced virulence in
the wax moth model, we performed random insertional mutagenesis in the Af293
genetic background to isolate mutants producing altered conidia colors. Strains
producing conidia of previously identified colors and of novel colors were
isolated. Interestingly, these color mutants displayed a higher level of
pathogenicity in the insect model compared to the wild type. Although some of
the more virulent color mutants showed increased resistance to hydrogen
peroxide, overall phenotypic characterizations including secondary metabolite
production, metalloproteinase activity, and germination rate did not reveal a
general mechanism accountable for the enhanced virulence of these color mutants
observed in the insect model. Our observations indicate instead, that
exacerbated immune response of the wax moth induced by increased exposure of
PAMPs (pathogen-associated molecular patterns) may cause self-damage that
results in increased mortality of larvae infected with the color mutants. The
current study underscores the limitations of using this insect model for
inferring the pathogenic potential of A. fumigatus strains in
mammals, but also points to the importance of understanding the innate immunity
of the insect host in providing insights into the pathogenicity level of
different fungal strains in this model. Additionally, our observations that
melanization defective color mutants demonstrate increased virulence in the
insect wax moth, suggest the potential of using melanization defective mutants
of native insect fungal pathogens in the biological control of insect
populations
Tissue elasticity and the ageing elastic fibre
The ability of elastic tissues to deform under physiological forces and to subsequently release stored energy to drive passive recoil is vital to the function of many dynamic tissues. Within vertebrates, elastic fibres allow arteries and lungs to expand and contract, thus controlling variations in blood pressure and returning the pulmonary system to a resting state. Elastic fibres are composite structures composed of a cross-linked elastin core and an outer layer of fibrillin microfibrils. These two components perform distinct roles; elastin stores energy and drives passive recoil, whilst fibrillin microfibrils direct elastogenesis, mediate cell signalling, maintain tissue homeostasis via TGFβ sequestration and potentially act to reinforce the elastic fibre. In many tissues reduced elasticity, as a result of compromised elastic fibre function, becomes increasingly prevalent with age and contributes significantly to the burden of human morbidity and mortality. This review considers how the unique molecular structure, tissue distribution and longevity of elastic fibres pre-disposes these abundant extracellular matrix structures to the accumulation of damage in ageing dermal, pulmonary and vascular tissues. As compromised elasticity is a common feature of ageing dynamic tissues, the development of strategies to prevent, limit or reverse this loss of function will play a key role in reducing age-related morbidity and mortality