On mechanism of quorum sensing in Candida albicans by 3(R)-hydroxy-tetradecaenoic acid.

Quorum sensing (QS) enables microorganisms to monitor their own density of population, and also their pathogenicity by intracellular signals, and synchronizing their specialized gene system in a particular cell density. QS system has been shown in Candida sp. as switching mechanism between successive phases in Candida cell morphology. The lag phase that occurs due to QS is commonly attributed to auto-stimulatory compounds, such as farnesol and farnesoic acid, which are released in the medium. The aim of this manuscript is to demonstrate the involvement of 3(R)-HTDE, a metabolite of linoleic acid, in the QS mechanism of Candida albicans. We show that 3(R)-HTDE, a ß-oxidation metabolite of endogenously present linoleic acid, accelerates cell morphogenesis in C. albicans, with alteration of gene expressions necessary for hyphal formation at right density of population utilizing aerobic pathway of endogenous lipid metabolism. We also explore the mechanistic underpinnings of the process where we are able to show that alteration of gene expressions are necessary for hyphal formation at the right population density which is achieved by the proper utilization of an aerobic pathway of endogenous lipid metabolism. In addition, we showed how this mediates biofilm formation itself, and the understanding of these mechanisms can be crucial in designing successful interventional strategies to combat Candida related infections.

Hepoxilin A3 (HXA3) synthase deficiency is causative of a novel ichthyosis form.

Non-bullous congenital ichthyosis erythroderma (NCIE) and lamellar ichthyosis (LI) are characterized by mutations in 12R-lipoxygenase (12R-LOX) and/or epidermal lipoxygenase 3 (eLOX3) enzymes. The eLOX3 lacks oxygenase activity, but is capable of forming hepoxilin-type products from arachidonic acid-derived hydroperoxide from 12R-LOX, termed 12R-hydroperoxyeicosa-5,8,10,14-tetraenoic acid (12R-HpETE). Mutations in either of two enzymes lead to NCIE or LI. Moreover, 12R-LOX-deficient mice exhibit severe phenotypic water barrier dysfunctions. Here, we demonstrate that 12R-HpETE can also be transformed to 8R-HXA(3) by hepoxilin A(3) (HXA(3)) synthase (12-lipoxygenase), which exhibits oxygenase activity. We also presented a novel form of ichthyosis in a patient, termed hepoxilin A(3) synthase-linked ichthyosis (HXALI), whose scales expressed high levels of 12R-LOX, but were deficient of HXA(3) synthase.

C. albicans activates cyclooxygenase but not its product prostaglandin E2in HPV 16-stabilized cells.

OBJECTIVE: The selective induction of cyclooxygenase-2 (COX-2) in human cells by Candida albicans was the first report of its role in infectious disease. This led us to question whether recurrent vulvovaginal candidosis in the cancer patient is involved in the formation of malignant tumors of the genital tract. Our speculation coincided with the patients' assessments in our hospital, where few cancer patients had a prior history of Candida infection. We wanted to study the contribution of C. albicans to gynecological cancers. STUDY DESIGN: In the present study, we used the developed vaginal epithelial cells system, having an insertion of HPV 16 viral sequence, as a model system (VK2/E6E7) to investigate the effect of Candida infection on prostaglandin E2 synthesis, which is known to be associated with cancers. We infected VK2/E6E7 cells with wild-type C. albicans and determined its effect on COX-2 and prostaglandin E2 synthesis, and its alteration in dependence on p53, and we analyzed the ubiquitin-proteasome degradation pathways and the involvement of 14-3-3 protein, which is involved in the modulation of the cell cycle. RESULTS: Our work using the cellular model indicates that recurrent Candida infection of the genital tract in patients carrying HPV 16 viral infection blocks the proliferation of host cells, PGE2 synthase expression and thus PGE2 production. CONCLUSION: We found that Candida infection contributes only to cell cycle arrest and does not by itself contribute actively to the development of cancer, although it is associated with patients diagnosed as having cancer of the genital tract induced by HPV 16 virus.