Aspartyl Proteinases of Eukaryotic Microbial Pathogens: From Eating to Heating

Cassone, Antonio; Vecchiarelli, Anna; Hube, Bernhard

doi:10.1371/journal.ppat.1005992

Cited by 27 publications

(24 citation statements)

References 46 publications

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“…Their reported resistance to VVC ( 1 ) can be overcome by increasing the size of the infectious inoculum, which could make the estrogen requirement less stringent ( 2 ). Mechanistically, the data obtained so far in our CD-1 model infected with high fungal inoculum are consistent with the well-established features of experimental vaginal candidiasis in typically susceptible mice: high levels of inflammatory markers, inability of the massively recruited neutrophils to clear the infection, possibly due to Candida or host-derived inhibitors, and role of one or more fungal aspartyl proteinases as inflammation inducers ( 1 , 4 – 7 ).…”

Section: Lettersupporting

confidence: 87%

Chronic Vaginal Candidiasis Is Achievable in Outbred CD-1 Mice

Gabrielli

Roselletti

Pericolini

et al. 2017

mBio

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Section: Lettersupporting

confidence: 87%

Chronic Vaginal Candidiasis Is Achievable in Outbred CD-1 Mice

Gabrielli

Roselletti

Pericolini

et al. 2017

mBio

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“…In addition, several virulence factors of the fungus, including the recently described Ece1, a source of Candida toxic active peptides (Moyes et al, 2016), are indeed inhibited in vivo during vaginal candidiasis. Indeed, the acceleration of C. albicans clearance and attenuation of inflammatory response following treatment with S. cerevisiae probiotic is likely due to direct inhibition of aspartyl proteases production and yeast-hypha transition, two factors considered of utmost importance in the pathogenesis of vaginal candidiasis (Cassone et al, 2016). These effects, in addition to those shown in vitro, and coupled with the absence of obvious cytotoxicity of the product, demonstrate that the probiotic activity of S. cerevisiae studied here is of high complexity, with multiple and possibly interacting factors.…”

Section: Please Cite This Article As 'In Press' Beneficial Microbesmentioning

confidence: 99%

Saccharomyces cerevisiae-based probiotic as novel anti-fungal and anti-inflammatory agent for therapy of vaginal candidiasis

Gabrielli

Pericolini

Ballet

et al. 2018

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Previously we demonstrated that the treatment with live Saccharomyces cerevisiae exerts beneficial therapeutic effects against vaginal candidiasis. Here, we address potential mechanisms particularly examining the probiotic capacity to modulate both fungus and host-related factors. We show that the S. cerevisiae-based probiotic markedly affects the expression of virulence traits of Candida albicans such as aspartyl proteinases (SAPs) as well as hyphae-associated proteins Hwp1 and Ece1 in the vaginal cavity. On the host side, the probiotic suppression of the influx of neutrophils caused by the fungus into the vaginas of the mice is likely related to: (1) lower production of interleukin-8; and (2) inhibition of SAPs expression. However, these neutrophils displayed reactive oxygen species hyperproduction and increased killing activity as compared to the neutrophils of placebo-treated mice. There was no evidence of any cytotoxic effect by the probiotic, either when used in vivo on vaginal epithelial cell and organ architecture, or in in vitro in human vaginal epithelium. Inactivated yeast cells did not affect any of the factors above. In summary, the data suggest that the beneficial effect exerted by this S. cerevisiae-based probiotic is the result of its interference with the expression of fungus virulence factors coupled with the modulation of the inflammatory response of the host.

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“…ASP5, an AP from the zoonotic parasite Toxoplasma gondii, was found to be located in the Golgi apparatus and plays a key role in the cleavage of GRA effectors at a PEXEL-like motif. Deletion of ASP5 resulted in reduced parasite fitness and virulence (Hammoudi et al 2015;Cassone et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Clade 5 aspartic proteases of Phytophthora infestans are virulence factors implied in RXLR effector cleavage

et al. 2019

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Late blight caused by the oomycete pathogen Phytophthora infestans is one of the most destructive diseases in potato cultivation. To successfully colonize its host, P. infestans secretes a suite of effector proteins that undermine plant immunity, many of which contain a conserved N-terminal RXLR motif that strongly resembles the host targeting motif in effectors of the malaria parasite Plasmodium falciparum. In this study, we focus on three P. infestans clade 5 aspartic proteases (PiAPs) that are homologous to Plasmepsin V (PMV), a Pl. falciparum AP responsible for cleaving effectors prior to translocation into red blood cells. Malaria parasites expressing mutated PMV are impaired in effector translocation and are less virulent. To determine whether clade 5 PiAPs play similar roles in virulence, we characterized P. infestans transformants with either reduced or enhanced PiAP expression levels. Phytophthora infestans transformants with altered PiAP10 or PiAP12 expression were found to be impaired in mycelial growth and sporangia production, and are hampered in their virulence on potato leaves. This was not observed in PiAP11 transformants. Activity assays showed that PiAP10 and PiAP12 possess moderate protease activity, and can potentially cleave the RXLR effector PiAVR4, but not a PiAVR4 version with a mutated RXLR motif. These findings imply that P. infestans APs function in the proteolytic cleavage of RXLR effectors, and warrant further investigation to verify and confirm the role of clade 5 PiAPs in effector processing.

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Aspartyl Proteinases of Eukaryotic Microbial Pathogens: From Eating to Heating

Cited by 27 publications

References 46 publications

Chronic Vaginal Candidiasis Is Achievable in Outbred CD-1 Mice

Chronic Vaginal Candidiasis Is Achievable in Outbred CD-1 Mice

Saccharomyces cerevisiae-based probiotic as novel anti-fungal and anti-inflammatory agent for therapy of vaginal candidiasis

Clade 5 aspartic proteases of Phytophthora infestans are virulence factors implied in RXLR effector cleavage

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