India is targeting malaria elimination by 2030. Understanding and adopting the strategies employed by countries that have successfully eliminated malaria can serve as a crucial thrust in this direction for a geographically diverse country like India. This analysis is based on extensive literature search on malaria elimination policies, strategies and programmes adopted by nine countries (China, El Salvador, Algeria, Argentina, Uzbekistan, Paraguay, Sri Lanka, Maldives and Armenia) which have attained malaria-free status over the past decade.
View Article and Find Full Text PDFExposure to the mold, Aspergillus, is ubiquitous and generally has no adverse consequences in immunocompetent persons. However, invasive and allergic aspergillosis can develop in immunocompromised and atopic individuals, respectively. Previously, we demonstrated that mouse lung eosinophils produce IL-17 in response to stimulation by live conidia and antigens of A.
View Article and Find Full Text PDFWe designed experiments to assess whether fungal cell wall mannans function as an immune shield or an immune agonist. Fungal cell wall β-(1,3)-glucan normally plays a major and dominant role in immune activation. The outer mannan layer has been variously described as an immune shield, because it has the potential to mask the underlying β-(1,3)-glucan, or an immune activator, as it also has the potential to engage with a wide range of mannose detecting PRRs.
View Article and Find Full Text PDFA correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
View Article and Find Full Text PDFGlycosylphosphatidylinositol (GPI)-anchored proteins are important for virulence of many pathogenic organisms including the human fungal pathogen, Candida albicans. GPI biosynthesis is initiated by a multi-subunit enzyme, GPI-N-acetylglucosaminyltransferase (GPI-GnT). We showed previously that two GPI-GnT subunits, encoded by CaGPI2 and CaGPI19, are mutually repressive.
View Article and Find Full Text PDFRas signaling in response to environmental cues is critical for cellular morphogenesis in eukaryotes. This signaling is tightly regulated and its activation involves multiple players. Sometimes Ras signaling may be hyperactivated.
View Article and Find Full Text PDFMicrobiology (Reading)
August 2017
Candida albicans is normally a harmless commensal of human beings, but it can cause superficial infections of the mucosa (oral/vaginal thrush) in healthy individuals and (rarely) infections of the skin or nails. It can also become invasive, causing life-threatening systemic and bloodstream infections in immunocompromised hosts, where the mortality rate can be as high as 50 %. It is the most common cause of serious fungal infection and is a common cause of nosocomial infections in hospitals.
View Article and Find Full Text PDFAspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17.
View Article and Find Full Text PDFCurr Opin Microbiol
December 2016
Candida albicans is a commensal coloniser of most people and a pathogen of the immunocompromised or patients in which barriers that prevent dissemination have been disrupted. Both the commensal and pathogenic states involve regulation and adaptation to the host microenvironment. The pathogenic potential can be downregulated to sustain commensalism or upregulated to damage host tissue and avoid and subvert immune surveillance.
View Article and Find Full Text PDFBackground & Objectives: Studies involving animal models of experimental tuberculosis have elucidated the predominant role of cytokines secreted by T cells and macrophages to be an essential component of the immune response against Mycobacterium tuberculosis infection. The immune activities of CD4+ T cells are mediated in part by Th1 cytokine interferon gamma (IFN-γ) which is produced primarily by T cells and natural killer (NK) cells and critical for initiating the immune response against intracellular pathogen such as M. tuberculosis.
View Article and Find Full Text PDFOdontomas are nonaggressive, hamartomatous developmental malformations composed of mature tooth substances and may be compound or complex depending on the extent of morphodifferentiation or on their resemblance to normal teeth. Among them, complex odontomas are relatively rare tumors. They are usually asymptomatic in nature.
View Article and Find Full Text PDFInterleukin-8 (IL-8) is a pleiotropic chemokine involved in metastasis and angiogenesis of breast tumors. The expression of IL-8 is deregulated in metastatic breast carcinomas owing to aberrant NF-κB activity, which is known to positively regulate IL-8 transcription. Earlier, we have shown that tumor suppressor SMAR1 suppresses NF-κB transcriptional activity by modulating IκBα function.
View Article and Find Full Text PDFGPI2 encodes for one of the six accessory subunits of the GPI-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the first step of GPI biosynthesis in S. cerevisiae and C. albicans.
View Article and Find Full Text PDFCandida albicans is a leading cause of fungal infections worldwide. It has several glycosylphosphatidylinositol (GPI)-anchored virulence factors. Inhibiting GPI biosynthesis attenuates its virulence.
View Article and Find Full Text PDFBackground: Proteins destined to be Glycosylphosphatidylinositol (GPI) anchored are translocated into the ER lumen completely before the C-terminal GPI anchor attachment signal sequence (SS) is removed by the GPI-transamidase and replaced by a pre-formed GPI anchor precursor. Does the SS have a role in dictating the conformation and function of the protein as well?
Methodology/principal Findings: We generated two variants of the Als5 protein without and with the SS in order to address the above question. Using a combination of biochemical and biophysical techniques, we show that in the case of Als5, an adhesin of C.
A novel co-regulation exists between the first step of GPI (glycosylphosphatidylinositol) anchor biosynthesis and the rate-determining step of ergosterol biosynthesis in Candida albicans. Depleting CaGpi19p, an accessory subunit of the enzyme complex that initiates GPI biosynthesis, down-regulates ERG11, altering ergosterol levels and drug response. This effect is specific to CaGpi19p depletion and is not due to cell wall defects or GPI deficiency.
View Article and Find Full Text PDFSearch for new antimicrobial agents led to the synthesis of series of N-1, C-3 and C-5 substituted bis-indoles. Their evaluation for antifungal and antibacterial activities resulted in the optimization of pyrrolidine/morpholine/N-benzyl moiety at the C-3 end and propane/butane/xylidine groups as linkers between two indoles for significant inhibition of microbial growth. Preliminary investigations have identified three highly potent antimicrobial agents.
View Article and Find Full Text PDFPIG-L/GPI12 proteins are endoplasmic reticulum-resident membrane proteins involved in the second step of glycosylphosphatidylinositol anchor biosynthesis in eukaryotes. We show that the Entamoeba histolytica PIG-L protein is optimally active in the acidic pH range. The enzyme has an intrinsic low level of de-N-acetylase activity in the absence of metal and is significantly stimulated by divalent cations.
View Article and Find Full Text PDFTo search multi drug resistance modulators, acridones carrying hydroxyl amine substituent at N-10 and COOH/Cl at C-4 were investigated for their interactions with the three components of efflux pump viz. P-gp, ATP, and Mg(2+). Experimental and theoretical results indicated that the compounds with COOH group at C-4 interact with P-gp and Mg(2+) while other set of compounds with Cl at C-4 interact with ATP and Mg(2+).
View Article and Find Full Text PDFIn order to search for MDR modulators, rationally designed acridone derivatives were investigated for their effect on influx or efflux of Rhodamine6G (R6G) in CAI4 cells. Results of these investigations indicate that in presence of compound 12, inhibition of growth of CAI4 cells and also an increased influx/efflux of R6G in CAI4 cells have been observed. This seems to be occurring due to the cell wall rupturing of Candida albicans.
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