The incidence of VVC by non- albicans Candida (NAC) species, such as C. parapsilosis , is increasing. Treatment failure is common in NAC-VVC because some species are resistant or poorly susceptible to the antifungal agents normally employed.

The fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeast Candida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain insight into a putative conservation of such a crucial process within opportunistic yeasts, we were particularly interested in studying the role of the PMR1 homolog in a low-virulent species that rarely causes candidiasis, Candida guilliermondii. We disrupted C. guilliermondii PMR1 and found that loss of Pmr1 affected cell growth and morphology, biofilm formation, susceptibility to cell wall perturbing agents, mannan levels, and the wall composition and organization. Despite there was a significant increment in the amount of β1,3-glucan exposed at the wall surface, this positively influenced only the ability of the mutant to stimulate IL-10 production by human monocytes, suggesting that recognition of both mannan and β1,3-glucan, is required to stimulate strong levels of pro-inflammatory cytokines. Accordingly, our results indicate C. guilliermondii sensing by monocytes was critically dependent on the recognition of N-linked mannans and β1,3-glucan, as reported in other Candida species. In addition, chemical remotion of cell wall O-linked mannans was found to positively influence the recognition of C. guilliermondii by human monocytes, suggesting that O-linked mannans mask other cell wall components from immune cells. This observation contrasts with that reported in C. albicans. Finally, mice infected with C. guilliermondii pmr1 null mutant cells had significantly lower fungal burdens compared to animals challenged with the parental strain. Accordingly, the null mutant showed inability to kill larvae in the Galleria mellonella infection model. This study thus demonstrates that mannans are relevant for the C. guilliermondii-host interaction, with an atypical role for O-linked mannans.

Aspartyl proteases are present in various organisms and, among virulent species, are considered major virulence factors. Host tissue and cell damage, hijacking of immune responses, and hiding from innate immune cells are the most common behaviors of fungal secreted proteases enabling pathogen survival and invasion.C. parapsilosis, an opportunistic human-pathogenic fungus mainly threatening low-birth weight neonates and children, possesses threeSAPPprotein-encoding genes that could contribute to the invasiveness of the species. Our results suggest thatSAPP1andSAPP2, but notSAPP3, influence host evasion by regulating cell damage, phagocytosis, phagosome-lysosome maturation, killing, and cytokine secretion. Furthermore,SAPP1andSAPP2also effectively contribute to complement evasion.

Dysregulation in the expression of miRNAs has been observed in various human cancers, including lung cancer. Recent studies have identified the role of a number of miRNAs in regulating key cellular processes and signaling pathways involved in lung tumourigenesis, including cell proliferation, differentiation, angiogenesis, apoptosis, invasion and metastasis. Due to their variable behavior and regulatory role in various nodal junctions in cellular pathways, miRNAs have also been used as potential therapeutic targets and clinical biomarkers in lung cancer. In this non-systematic review, we briefly focus on biogenesis and function of cytoplasmic miRNA and the role of methylation in the regulation of miRNA biogenesis in non-small cell lung cancer (NSCLC). Further, we elaborate the role of differentially expressed miRNAs and their regulatory role on various signaling pathways, cell cycle, and apoptosis in NSCLC.