Current Issue : October - December Volume : 2015 Issue Number : 4 Articles : 6 Articles
Microbial infections till date remain a scourge of humanity due to lack of vaccine against some infections, emergence of drug\nresistant phenotypes, and the resurgence of infections amongst others. Continuous quest for novel therapeutic approaches remains\nimperative. Here we (i) assessed the effects of extracts/hydro lates of some medicinal plants on pathogenic microorganisms and\n(ii) evaluated the inhibitory potential of the most active ones in combination with antibiotics. Extract E03 had the highest DZI\n(25 mm). Extracts E05 and E06 were active against all microorganisms tested.The MICs and MBCs of the methanol extracts ranged\nfrom 16.667 Ã?â?? 103\n????g/mL to 2 ????g/mL and hydro lates from 0.028 to 333333 ppm. Extract E30 had the highest activity especially\nagainst S. saprophyticus (MIC of 6 ppm) and E. coli (MIC of 17 ppm). Combination with conventional antibiotics was shown to\novercome resistance especially with E30. Analyses of the extracts revealed the presence of alkaloids, flavonoids, triterpenes, steroids,\nphenols, and saponins. These results justify the use of these plants in traditional medicine and the practice of supplementing\ndecoctions/concoctions with conventional antibiotics. Nauclea pobeguinii (E30), the most active and synergistic of all these extracts,\nand some hydro lates with antimicrobial activity need further exploration for the development of novel antimicrobials....
Objective of this research was to investigate the presence of antimicrobial compound as a secondary metabolite by the endophytes isolated from Alpinea galanga willd., rhizome. Isolation of endophytic fungi was carried out using screening methods. Characterization of the organism was performed morphologically and biochemically. Extraction and identification of secondary metabolite was performed using standard analytical methods. Antifungal activity was done using agar diffusion method. Nine different endophytes were isolated from rhizomes. One of the endophyte was identified as Aspergillus terrious MTCC11987. The culture was deposited at MTCC, Chandigarh, India. The organism was found to be positive for amylase, catalase and cellulase enzyme production. Antifungal activity against Saccharomyces cerevisiae and Candida albicans with zone diameters of 12.5 and 14 mm respectively were observed for the broth. The broth showed U.V. absorption maxima at 245 nm. TLC of the broth showed Rf of 0.72 near to reference sample. FTIR and 1H NMR data reveals the presence of lovastatin in open ring form in the isolated sample. This study confirms the ability of Aspergillus terrious MTCC11987 isolated from Alpine galanga to produce lovastatin. The statin produced was effective on Saccharomyces cerevisiae and Candida albicans. Hence it can be predicted that the antimicrobial and hypolipidimic activity of Alpinea galanga rhizomes is synergistically affected by the endophyte. Further the mechanism that exactly determines the synergism of the endophyte has to be derived....
The echinocandin antifungal drug caspofungin at high concentrations reverses the growth inhibition of Aspergillus fumigatus, a\nphenomenon known as the ââ?¬Å?paradoxical effect,ââ?¬Â which is not consistently observed with other echinocandins (micafungin and\nanidulafungin). Previous studies of A. fumigatus revealed the loss of the paradoxical effect following pharmacological or genetic\ninhibition of calcineurin, yet the underlying mechanism is poorly understood. Here, we utilized a codon-optimized bioluminescent\nCa2 reporter aequorin expression system in A. fumigatus and showed that caspofungin elicits a transient increase in cytosolic\nfree Ca2 ([Ca2]c) in the fungus that acts as the initial trigger of the paradoxical effect by activating calmodulin-calcineurin\nsignaling. While the increase in [Ca2]c was also observed upon treatment with micafungin, another echinocandin without\nthe paradoxical effect, a higher [Ca2]c increase was noted with the paradoxical-growth concentration of caspofungin. Treatments\nwith a Ca2-selective chelator, BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N=,N=-tetraacetic acid], or the L-type Ca2\nchannel blocker verapamil abolished caspofungin-mediated paradoxical growth in both the wild-type and the echinocandinresistant\n(EMFR-S678P) strains. Concomitant with increased [Ca2]c levels at higher concentrations of caspofungin, calmodulin\nand calcineurin gene expression was enhanced. Phosphoproteomic analysis revealed that calcineurin is activated through phosphorylation\nat its serine-proline-rich region (SPRR), a domain previously shown to be essential for regulation of hyphal growth,\nonly at a paradoxical-growth concentration of caspofungin. Our results indicate that as opposed to micafungin, the increased\n[Ca2]c at high concentrations of caspofungin activates calmodulin-calcineurin signaling at both a transcriptional and a posttranslational\nlevel and ultimately leads to paradoxical fungal growth....
Background: A triple antibiotic mixture (ciprofloxacin; CF, metronidazole; MN, and minocycline; MC) has been used\nfor dental root canal medicaments in pulp regeneration therapy. However, tooth discolorations, cervical root\nfractures, and inadequate pulp-dentin formation have been reported due to the triple antibiotic regimen. Therefore,\nan antibiotic encapsulated biomimetic nanomatrix gel was developed to minimize the clinical limitations and\nmaximize a natural healing process in root canal infections. In this study, minimal bacterial concentrations (MBC) of\nthe selected antibiotics (CF and MN) were tested in 14 representative endodontic bacterial species. Then MBC of\neach CF and MN were separately encapsulated within the injectable self-assembled biomimetic nanomatrix gel to\nevaluate antibacterial level on Enterococcus faecalis and Treponema denticola.\nResults: Antibiotic concentrations lower than 0.2 ?g/mL of CF and MN demonstrated antibacterial activity on the\n14 endodontic species. Furthermore, 6 different concentrations of CF and MN separately encapsulated with the\ninjectable self-assembled biomimetic nanomatrix gel demonstrated antibacterial activity on Enterococcus faecalis\nand Treponema denticola at the lowest tested concentration of 0.0625 ?g/mL.\nConclusions: These results suggest that each CF and MN encapsulated within the injectable self-assembled biomimetic\nnanomatrix gel demonstrated antibacterial effects, which could be effective for the root canal disinfection while\neliminating MC. In the long term, the antibiotic encapsulated injectable self-assembled biomimetic nanomatrix\ngel can provide a multifunctional antibiotic delivery method with potential root regeneration. Further studies are\ncurrently underway to evaluate the effects of combined CF and MN encapsulated within the injectable\nself-assembled biomimetic nanomatrix gel on clinical samples....
The antifungal drug posaconazole has shown significant activity against Trypanosoma cruzi in vitro and in experimental murine\nmodels. Despite this, in a recent clinical trial it displayed limited curative potential. Drug testing is problematic in experimental\nChagas disease because of difficulties in demonstrating sterile cure, particularly during the chronic stage of infection when parasite\nburden is extremely low and tissue distribution is ill defined. To better assess posaconazole efficacy against acute and chronic\nChagas disease, we have exploited a highly sensitive bioluminescence imaging system which generates data with greater accuracy\nthan other methods, including PCR-based approaches. Mice inoculated with bioluminescent T. cruzi were assessed by in vivo\nand ex vivo imaging, with cyclophosphamide-induced immunosuppression used to enhance the detection of relapse. Posaconazole\nwas found to be significantly inferior to benznidazole as a treatment for both acute and chronic T. cruzi infections. Whereas\n20 days treatment with benznidazole was 100% successful in achieving sterile cure, posaconazole failed in almost all cases. Treatment\nof chronic infections with posaconazole did however significantly reduce infection-induced splenomegaly, even in the absence\nof parasitological cure. The imaging-based screening system also revealed that adipose tissue is a major site of recrudescence\nin mice treated with posaconazole in the acute, but not the chronic stage of infection. This in vivo screening model for\nChagas disease is predictive, reproducible and adaptable to diverse treatment schedules. It should provide greater assurance that\ndrugs are not advanced prematurely into clinical trial....
The biosynthesis of natural products by heterologous\nexpression of biosynthetic pathways in amenable production\nstrains enables biotechnological access to a variety\nof valuable compounds by conversion of renewable resources.\nPseudomonas putida has emerged as a microbial laboratory\nwork horse, with elaborated techniques for cultivation and\ngenetic manipulation available. Beyond that, this bacterium\noffers several particular advantages with regard to natural\nproduct biosynthesis, notably a versatile intrinsic metabolism\nwith diverse enzymatic capacities as well as an outstanding\ntolerance to xenobiotics. Therefore, it has been applied for\nrecombinant biosynthesis of several valuable natural products.\nThis review provides an overview of applications of P. putida\nas a host organism for the recombinant biosynthesis of such\nnatural products, including rhamnolipids, terpenoids,\npolyketides and non-ribosomal peptides, and other amino\nacid-derived compounds. The focus is on de novo natural\nproduct synthesis from intrinsic building blocks by means of\nheterologous gene expression and strain engineering. Finally,\nthe future potential of the bacterium as a chassis organism for\nsynthetic microbiology is pointed out....
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