Biology subjects

Aubry, L.

Publications and source records attributed to Aubry, L..

3 recordsLinked to original sources

bioRxiv2023

Upc2-mediated mechanisms of azole resistance in Candida auris

Candida auris is an emerging yeast pathogen of major concern because of its ability to cause hospital outbreaks of invasive candidiasis and to develop resistance to antifungal drugs. A majority of C. auris isolates are resistant to fluconazole, a first-line treatment of invasive candidiasis. Mechanisms of azole resistance are multiple, including mutations in the target gene ERG11 and activation of the transcription factors Tac1b and Mrr1, which control the drug transporters Cdr1 and Mdr1, respectively. In this study, we investigated the role the transcription factor Upc2, which is known to regulate the ergosterol biosynthesis pathway and azole resistance in other Candida spp. Genetic deletion and hyperactivation of Upc2 by epitope tagging in C. auris resulted in drastic increased and decreased susceptibility to azoles, respectively. This effect was conserved in strains with genetic hyperactivation of Tac1b or Mrr1. Reverse transcription PCR analyses showed that Upc2 regulates ERG11 expression and also activates the Mrr1/Mdr1 pathway. We showed that upregulation of MDR1 by Upc2 could occur independently from Mrr1. The impact of UPC2 deletion on MDR1 expression and azole susceptibility in a hyperactive Mrr1 background was stronger than that of MRR1 deletion in a hyperactive Upc2 background. While Upc2 hyperactivation resulted in a significant increase of expression of TAC1b, CDR1 expression remained unchanged. Taken together, our results showed that Upc2 is crucial for azole resistance in C. auris, via regulation of the ergosterol biosynthesis pathway and activation of the Mrr1/Mdr1 pathway. Notably, Upc2 is a very potent and direct activator of Mdr1.

microbiology↗

bioRxiv2023

Reduction, removal or replacement of sodium nitrite in a model of cured and cooked meat: a joint evaluation of consequences on microbiological issues in food safety, colon ecosystem and colorectal carcinogenesis

ScopeEpidemiological and experimental evidence reported that processed meat consumption is associated with colorectal cancer (CRC) risk. Several studies suggest the involvement of nitrite or nitrate additives via N-nitroso-compound formation (NOCs). Methods and resultsCompared to the reference level (120 mg/kg of ham), the effects of sodium nitrite reduction (90 mg/kg of ham), removal and replacement were analysed on ham characteristics and in a CRC rat model. Sodium nitrite removal and reduction induced a similar decrease in CRC preneoplastic lesions, but only reduction led to (i) an inhibitory effect on Listeria monocytogenes growth comparable to that obtained using the reference nitrite level of 120 mg/kg and (ii) an effective control of lipid peroxidation. Among the three alternatives tested, none led to a significant gain when compared to the 120 mg/kg ham reference level: vegetable stock, due to nitrate presence, was very similar to this reference nitrite level, yeast extract induced a strong luminal peroxidation and no decrease in preneoplastic lesions despite the absence of NOCs, and polyphenol rich extract induced the clearest downward trend on preneoplastic lesions but the concomitant presence of nitrosyl iron in feces. Except vegetable stock, other alternatives were less efficient than sodium nitrite ([≥] 90 mg/kg) in reducing L. monocytogenes growth. ConclusionNitrite reduction (90mg/kg) effectively reduced CRC risk through limiting NOC formation and lipid peroxidation, while mitigating L. monocytogenes risks from cooked hams. Going further in reduction should be possible if accompanied by antioxidants to limit lipid peroxidation and appropriate use-by dates.

pathology↗

bioRxiv2019

When the going gets tough, the tough get going: effect of extreme climate on an Antarctic seabird’s life history

1Individuals differ in many ways. Most produce few offspring; a handful produce many. Some die early; others live to old age. It is tempting to attribute these differences in out-comes to differences in individual traits, and thus in the demographic rates experienced. However, there is more to individual variation than meets the eye of the biologist. Even among individuals sharing identical traits, life history outcomes will vary due to individual stochasticity, i.e., to chance. Quantifying the contributions of heterogeneity and chance is essential to understanding natural variability. Inter-individual differences vary across environmental conditions. Heterogeneity and stochasticity depend on environmental conditions. We show that favorable conditions increase the contributions of individual stochasticity, and reduce the contributions of heterogeneity, to variance in demographic outcomes in a seabird population. The opposite is true under poor conditions. This result has important consequence for understanding the ecology and evolution of life history strategies.

ecology↗