IL10 Variant g.5311A Is Associated with Visceral Leishmaniasis in Indian Population

BackgroundVisceral leishmaniasis (VL) is a multifactorial disease, where the host genetics play a significant role in determining the disease outcome. The immunological role of anti-inflammatory cytokine, Interleukin 10 (IL10), has been well-documented in parasite infections and considered as a key regulatory cytokine for VL. Although VL patients in India display high level of IL10 in blood serum, no genetic study has been conducted to assess the VL susceptibility / resistance. Therefore, the aim of this study is to investigate the role of IL10 variations in Indian VL; and to estimate the distribution of disease associated allele in diverse Indian populations.MethodologyAll the exons and exon-intron boundaries of IL10 were sequenced in 184 VL patients along with 172 ethnically matched controls from VL endemic region of India.

Result and Discussion

Our analysis revealed four variations; rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron), rs3024496 (4976 T>C, 3’ UTR) and rs3024498 (5311 A>G, 3’ UTR). Of these, a variant g.5311A is significantly associated with VL (χ²=18.87; p =0.00001). In silico approaches have shown that a putative micro RNA binding site (miR-4321) is lost in rs3024498 mRNA. Further, analysis of the above four variations in 1138 individuals from 34 ethnic populations, representing different social and linguistic groups who are inhabited in different geographical regions of India, showed variable frequency. Interestingly, we have found, majority of the tribal populations have low frequency of VL (‘A’ of rs3024498); and high frequency of leprosy (‘T’ of rs1554286), and Behcet’s (‘A’ of rs1518111) associated alleles, whereas these were vice versa in castes. Our findings suggest that majority of tribal populations of India carry the protected / less severe allele against VL, while risk / more severe allele for leprosy and Behcet’s disease. This study has potential implications in counseling and management of VL and other infectious diseases.     

Antifungal Potential of Plant Growth Promoting Bacillus Species Against Blossom Blight of Rose

Blossom blight caused by Botrytis cinerea is one among the most devastating diseases that cause complete post-harvest loss in flower crops. The present study focuses on the development of effective bioformulation towards suppression of blossom blight and plant growth promotion in rose. Bacillus amyloliquefaciens (VB2) and Bacillus subtilis (AP) effectively inhibited mycelial growth of B. cinerea in vitro. Genome screening of VB2 and AP revealed the presence of antimicrobial peptide genes including, ituD, ipa14, bacA, bacD, srfA, sfP, spaC, spaS responsible for the biosynthesis of antibiotics such as iturin, bacilysin, bacillomycin, surfactin and subtilin. Further, the presence of volatile antifungal compounds in the bacterial secretome was identified through gas chromatography–mass spectrometry (GC/MS) analysis. Upon treatment, AP accelerated the metabolite profile of the plants and a rise in peak area of antifungal compounds such as, pentadecanoic acid, n-hexadecanoic acid, octadecanoic acid (stearic acid) and tetradecanoic acid was observed. In vitro, VB2 produced maximum indole acetic acid (9.17 µg/ml) and gibberellic acid (8.20 µg/ml) in nutrient broth. Under field conditions, foliar spray of VB2 at 0.5% (5 ml/l), four times at weekly interval suppressed blossom blight incidence (64% reduction over control) and also promoted yield. Future research towards development of an effective bioformulation with extended shelf life will aid in the management of various fungal, bacterial and viral diseases in different crop plants.

     

Sea Anemones as Potential Source for Bioactive Metabolites

International Journal of Peptide Research and Therapeutics - Marine organisms are novel sources for biologically active compounds which are potentially valuable materials in biomedical research. In...     

Validation of potential inhibitors for SrtA against Bacillus anthracis by combined approach of ligand-based and molecular dynamics simulation

The development of SrtA inhibitors targeting the biothreat organism namely Bacillus anthracis was achieved by the combined approach of pharmacophore modeling, binding interactions, electron transferring capacity, ADME, and Molecular dynamics studies. In this study, experimentally reported Ba-SrtA inhibitors (pyridazinone and pyrazolethione derivatives) were considered for the development of enhanced pharmacophoric model. The obtained AAAHR hypothesis was a pure theoretical concept that accounts for common molecular interaction network present in experimentally active pyridazinone and pyrazolethione derivatives. Pharmacophore-based screening of AAAHR hypothesis provides several new compounds, and those compounds were treated with four phases of docking protocols with combined Glide-QPLD docking approach. In this approach, scoring and charge accuracy variations were seen to be dominated by QM/MM approach through the allocation of partial charges. Finally, we reported the best compounds from binding db, Chembridge db, and Toslab based on scoring values, energy parameters, electron transfer reaction, ADME, and cell adhesion inhibition activity. The dynamic state of interaction and binding energy assess that new compounds are more active inside the binding pocket and these compounds on experimental validations will survive as better inhibitors for targeting the cell adhesion mechanism of Ba-SrtA.