Vaginal candidiasis is an extremely common disease predominantly caused by four phylogenetically diverse species: Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis.Using a time course infection model of vaginal epithelial cells and dual RNA-Sequencing, we show that these species exhibit distinct pathogenicity patterns, defined by highly species-specific transcriptional profiles during infection of vaginal epithelial cells. In contrast, host cells exhibit a homogeneous response to all species at early stages of infections, which is characterized by sublethal mitochondrial signalling inducing a protective type I interferon response. At later stages, the transcriptional response of the host diverges in a species-dependent manner. This divergence is primarily driven by the extent of epithelial damage elicited by species-specific mechanisms such as secretion of the toxin candidalysin by C. albicans. Our results uncover a dynamic, biphasic response of vaginal epithelial cells to Candida species, characterized by protective mitochondriaassociated type I interferon signalling and a species-specific damage-driven response.
Most of colorectal cancer CRC-related death is due to metastasis and the finding of markers for prognosis of invasiveness, constitutes an appealing challenge. Here, after analysing cDNA array containing 43 tumour and 5 normal mucosa samples, we report that the expression of the
ZNF518B
gene as a whole and that of its two major splicing isoforms are significantly increased in tumours. The canonical isoform was also up-regulated in a patients’ cohort containing 70 tumour and 69 adjacent tissue samples. The effects of silencing
ZNF518B
on the phenotype of CRC cell lines were then studied. The gene does not affect cell proliferation, but plays a significant role in cell migration and invasiveness and induces changes in the epithelial-to-mesenchymal transition markers, suggesting that
ZNF518B
favours tumour cell dissemination. To study the regulation of the gene, transcription-related changes in nucleosomal organisation and epigenetic marks around the transcriptional start site were analysed. The positioning of a nucleosome over the transcription start site and the differential presence of the epigenetic marks H3K9ac, H3K27ac, H3K4me3 and H3K9me3 correlate with gene expression. Inhibition of histone deacetylases increases the transcription of
ZNF518B
, which may be a candidate for invasiveness prognosis in CRC and a target for epigenetic drugs.
Opportunistic commensal and environmental fungi can cause superficial to systemic diseases in humans. But how did these pathogens adapt to infect us and how does host-pathogen co-evolution shape their virulence potential? During evolution toward pathogenicity, not only do microorganisms gain virulence genes, but they also tend to lose non-adaptive genes in the host niche. Additionally, virulence factors can become detrimental during infection when they trigger host recognition. The loss of non-adaptive genes as well as the loss of the virulence potential of genes by adaptations to the host has been investigated in pathogenic bacteria and phytopathogenic fungi, where they are known as antivirulence and avirulence genes, respectively. However, these concepts are nearly unknown in the field of pathogenic fungi of humans. We think that this unnecessarily limits our view of human-fungal interplay, and that much could be learned if we applied a similar framework to aspects of these interactions. In this review, we, therefore, define and adapt the concepts of antivirulence and avirulence genes for human pathogenic fungi. We provide examples for analogies to antivirulence genes of bacterial pathogens and to avirulence genes of phytopathogenic fungi. Introducing these terms to the field of pathogenic fungi of humans can help to better comprehend the emergence and evolution of fungal virulence and disease.
Candida glabrata
is an opportunistic pathogen whose incidence has been increasing in the last 40 years. It has risen to become the most prominent non-
Candida albicans
Candida
(NCAC) species to cause candidemia, constituting about one-third of isolates in the United States, and steadily increasing in European countries and in Australia.
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