Strain variation in gene expression impact of hyphal cyclin Hgc1 in <i>Candida albicans</i>

Sharma, Anupam; Mitchell, Aaron P.

doi:10.1093/g3journal/jkad151

Cited by 5 publications

(2 citation statements)

References 24 publications

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“…Our rationale is that some functionally important gene expression responses may be heterogeneous or transient and thus may fall below a specific fold-change in one strain. This approach previously indicated that the gene expression impact of hgc1 Δ/Δ and efg1 Δ/Δ mutations in these strain backgrounds correlates well ( R 2 of 0.75 and 0.79, respectively), while that of an nrg1 Δ/Δ mutation correlates poorly ( R 2 of 0.38) ( 15 ). Here, we found that the low-iron responses correlated well, with an R 2 of 0.83 for 820 genes (Fig.…”

Section: Resultsmentioning

confidence: 98%

Strain variation in the Candida albicans iron limitation response

Xiong,

Goerlich,

et al. 2024

mSphere

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Iron acquisition is critical for pathogens to proliferate during invasive infection, and the human fungal pathogen Candida albicans is no exception. The iron regulatory network, established in reference strain SC5314 and derivatives, includes the central player Sef1, a transcription factor that activates iron acquisition genes in response to iron limitation. Here, we explored potential variation in this network among five diverse C. albicans strains through mutant analysis, Nanostring gene expression profiling, and, for two strains, RNA-Seq. Our findings highlight four features that may inform future studies of natural variation and iron acquisition in this species. (i) Conformity: In all strains, major iron acquisition genes are upregulated during iron limitation, and a sef1 Δ/Δ mutation impairs that response and growth during iron limitation. (ii) Response variation: Some aspects of the iron limitation response vary among strains, notably the activation of hypha-associated genes. As this gene set is tied to tissue damage and virulence, variation may impact the progression of infection. (iii) Genotype-phenotype variation: The impact of a sef1 Δ/Δ mutation on cell wall integrity varies, and for the two strains examined the phenotype correlated with sef1 Δ/Δ impact on several cell wall integrity genes. (iv) Phenotype discovery: DNA repair genes were induced modestly by iron limitation in sef1 Δ/Δ mutants, with fold changes we would usually ignore. However, the response occurred in both strains tested and was reminiscent of a much stronger response described in Cryptococcus neoformans , a suggestion that it may have biological meaning. In fact, we observed that the iron limitation of a sef1 Δ/Δ mutant caused recessive phenotypes to emerge at two heterozygous loci. Overall, our results show that a network that is critical for pathogen proliferation presents variation outside of its core functions. IMPORTANCE A key virulence factor of Candida albicans is the ability to maintain iron homeostasis in the host where iron is scarce. We focused on a central iron regulator, SEF1 . We found that iron regulator Sef1 is required for growth, cell wall integrity, and genome integrity during iron limitation. The novel aspect of this work is the characterization of strain variation in a circuit that is required for survival in the host and the connection of iron acquisition to genome integrity in C. albicans .

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Section: Resultsmentioning

confidence: 98%

Strain variation in the Candida albicans iron limitation response

Xiong,

Goerlich,

et al. 2024

mSphere

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“…A limitation of forward genetic screening is the time-consuming nature of preparing a library of defined mutants, which means that mutant collections are generally only made in a single-strain background. Recent work on strain variation in fungi has demonstrated significant differences in phenotypes between the same deletion or mutation in different strain backgrounds ( 30 – 33 ). As described above for the lncRNA DINOR ( 6 ) , important validation steps can include making the deletion in multiple strain or clade backgrounds to determine the conservation of the phenotype.…”

Section: Mapping Of Hitsmentioning

confidence: 99%

Going fishing: how to get what you want from a fungal genetic screen

O'Meara

2024

mSphere

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Five years ago, as I was starting my lab, I wrote about two functional genomic screens in fungi that had inspired me (mSphere 4:e00299-19, https://doi.org/10.1128/mSphere.00299-19 ). Now, I want to discuss some of the principles and questions that I ask myself and my students as we embark on our own screens. A good screen, whether it is a genetic or chemical screen, can be the starting point for new discovery and an excellent basis for the beginning of a scientific research project. However, screens are often criticized for being “fishing expeditions.” To stretch this metaphor to the extreme, this is because people are worried that we do not know how to fish, that we will come home without any fish, bring home the wrong fish, or not know what to do with a fish if we caught it. How you set up the screen and analyze the results determines whether the screen will be useful. In this mini-review, and in the spirit of teaching a scientist to fish, I will discuss recent excellent fungal genetic and chemical screens that illustrate some of the key aspects of a successful screen.

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Identification of an active RNAi pathway in Candida albicans

Iracane,

Arias-Sardá,

Maufrais

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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RNA interference (RNAi) is a fundamental regulatory pathway with a wide range of functions, including regulation of gene expression and maintenance of genome stability. Although RNAi is widespread in the fungal kingdom, well-known species, such as the model yeast Saccharomyces cerevisiae , have lost the RNAi pathway. Until now evidence has been lacking for a fully functional RNAi pathway in Candida albicans , a human fungal pathogen considered critically important by the World Health Organization. Here, we demonstrated that the widely used C. albicans reference strain (SC5314) contains an inactivating missense mutation in the gene encoding for the central RNAi component Argonaute. In contrast, most other C. albicans isolates contain a canonical Argonaute protein predicted to be functional and RNAi-active. Indeed, using high-throughput small and long RNA sequencing combined with seamless CRISPR/Cas9-based gene editing, we demonstrate that an active C. albicans RNAi machinery represses expression of subtelomeric gene families. Thus, an intact and functional RNAi pathway exists in C. albicans , highlighting the importance of using multiple reference strains when studying this dangerous pathogen.

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Strain variation in gene expression impact of hyphal cyclin Hgc1 in Candida albicans

Cited by 5 publications

References 24 publications

Strain variation in the Candida albicans iron limitation response

Strain variation in the Candida albicans iron limitation response

Going fishing: how to get what you want from a fungal genetic screen

Identification of an active RNAi pathway in Candida albicans

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