Eugenol exhibits anti-virulence properties by competitively binding to quorum sensing receptors

The primary objective of this study was to ascertain the anti-biofilm and anti-virulence properties of sub-minimum inhibitory concentration (MIC) levels of eugenol against the standard strain PAO1 and two multi-drug resistant P. aeruginosa clinical isolates utilizing quorum sensing inhibition (QSI). Eugenol at 400 μM significantly reduced biofilm formation on urinary catheters and the virulence factors (VF) including extracellular polysaccharides, rhamnolipid, elastase, protease, pyocyanin, and pyoverdine (p < 0.001). Further, eugenol exhibited a marked effect on the production of QS signals (AIs) (p < 0.001) without affecting their chemical integrity. In silico docking studies demonstrated a stable molecular binding between eugenol and QS receptor(s) in comparison with respective AIs. Investigation on reporter strains confirmed the competitive binding of eugenol to a QS receptor (LasR) as the possible QSI mechanism leading to significant repression of QS associated genes besides the VF genes (p < 0.001). This study provides insights, for the first time, into the mechanism of the anti-virulence properties of eugenol.     

Dysregulated expression of microRNAs in aqueous humor from intraocular tuberculosis patients

Molecular Biology Reports - Systemic Mycobacterium tuberculosis (Mtb) infection alters microRNA’s expression that controls cellular processes and modulates host defense mechanisms. However,...     

Comparative transcriptome analyses provide novel insights into the differential response of Pigeonpea (Cajanus cajan L.) and its wild relative (Cajanus platycarpus (Benth.) Maesen) to herbivory by Helicoverpa armigera (Hübner)

Plant Molecular Biology - We demonstrate that the C-terminus of OsCDC48 is essential for maintaining its full ATPase activity and OsCDC48/48E interaction is required to modulate cellular processes...     

Development and standardization of cyst based liquid formulation of Azospirillum bioinoculant

Azospirillum bioinoculant is well known for its high nitrogen fixing and plant growth promoting characters. The carrier based bioinoculants generally suffer from shorter shelf life, poor quality, high contamination and low field performance. Therefore, it is necessary to develop alternative new formulation of inoculants where cyst based inoculants can play significant role. The cyst based liquid formulation was developed by inoculating Azospirillum into the cyst inducing minimal salts medium (MSM). One hundred per cent conversion of vegetative cells into cyst cells was noticed in 96 h. The survival of cyst cells in the MSM was observed up to one year and two months and interestingly, the population level of 10(8) was maintained till the final observation. The cyst cells of Azospirillum accumulated poly-beta-hydroxybutyrate (PHB) granules and exhibited desiccation tolerance up to 20 days and temperature tolerance up to 40 degrees C. Thus the cyst based liquid formulation has twin advantage of longer shelf life and tolerance to harmful environmental conditions. Regeneration of cyst cells into vegetative cells in different media viz., tap water, sterile water, rice gruel and nutrient broth was studied. The changes started within 3 h and complete return of vegetative cells was observed at 24 h. Although all the media tested favoured regeneration, comparatively quicker regeneration was observed in nutrient broth and followed by rice gruel. Thus, cyst based liquid formulation of Azospirillum has all the survival advantages and can be used as a potential bioinoculant.     

Protective effect of Dunaliella salina (Volvocales, Chlorophyta) against experimentally induced fibrosarcoma on wistar rats

The beta-carotene-yielding microalga, Dunaliella salina (Dunal) Teod. maintained in De Walne's medium was harvested and lyophilized. Fibrosarcoma was induced in rats by 20-methylcholanthrene. 0.5 g and 1.0 g of lyophilized D. salina powder was administered to the rats orally through carboxy methyl cellulose. Cisplatin was administered along with vitamin E to compare the protective effect of D. salina against fibrosarcoma. Administration of D. salina decreased the levels of cholesterol and lactate dehydrogenase as well as the activities of catalase, superoxide dismutase, serum aspartate aminotransaminase, serum alanine aminotransferase, when compared to control. A significant reduction in the levels of hepatic and renal RNA and DNA was observed in the sarcoma rats when treated with D. salina powder. Histopathological studies of tumor tissues showed regenerative and regressive changes. beta-carotene globules isolated from the powder of Dunaliella salina confirmed the presence of 9-cis-beta-carotene and all-trans-beta-carotene.     

Dendritic cells from C57BL/6 mice undergo activation and induce Th1-effector cell responses against Campylobacter jejuni

Food-borne Campylobacter jejuni (Cj) is an important cause of enteritis. We showed that C57BL/6 and congenic interleukin (IL)-10(-/-) mice serve as models of Cj colonization and enteritis, respectively. Thus, C57BL/6 mice are resistant to Cj induced disease. Because dendritic cells (DCs) are central to regulating adaptive immune responses, we investigated the interaction of Cj with murine bone marrow-derived DCs (BM-DCs) to assess bacterial killing, DC activation, and the ability of Cj-infected BM-DCs to stimulate Campylobacter-specific T cell responses in vitro. BM-DCs challenged with Cj efficiently internalized and killed Cj 11168 and significantly upregulated surface MHC-II, CD40, CD80 and CD86 demonstrating a mature phenotype. Infected BM-DCs secreted significant amounts of tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-12p70. Formalin-killed Cj also induced maturation of BM-DCs with similar cytokine production but at a significantly lower magnitude than live bacteria. Maximal activation of murine BM-DCs required internalization of Cj; attachment alone was not sufficient to elicit significant responses. Also, various strains of Cj elicited different magnitudes of cytokine production from BM-DCs. Finally, in a coculture system, Cj-infected BM-DCs induced high level interferon-gamma (INF-gamma) production from CD4+T cells indicating Th1 polarization. Thus, DCs from resistant C57BL/6 mice initiate T cell responses against Cj.     

IL-10 Dependent Suppression of Type 1, Type 2 and Type 17 Cytokines in Active Pulmonary Tuberculosis

Background

Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB), their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL) and latent tuberculosis (LTB) have not been well studied.

Aim and Methods

To identify cytokine responses associated with pulmonary tuberculosis (TB), TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA.

Results

PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFNγ, TNFα and IL-2); Type 2 (IL-4) and Type 17 (IL-17A and IL-17F) cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFNγ responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFNγ, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially) the suppression of cytokine responses in PTB.

Conclusion

Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB.