125 research outputs found
Plant-derived antimicrobials to fight against multi-drug-resistant human pathogens
Antibiotic resistance is becoming a pivotal concern for public health that has accelerated the search for new antimicrobial molecules from nature. Numbers of human pathogens have inevitably evolved to become resistant to various currently available drugs causing considerable mortality and morbidity worldwide. It is apparent that novel antibiotics are urgently warranted to combat these life-threatening pathogens. In recent years, there have been an increasing number of studies to discover new bioactive compounds from plant origin with the hope to control antibiotic-resistant bacteria. This review attempts to focus and record the plant-derived compounds and plant extracts against multi-drug-resistant (MDR) pathogens including methicillin-resistant Staphylococcus aureus (MRSA), MDR-Mycobacterium tuberculosis and malarial parasites Plasmodium spp. reported between 2005 and 2015. During this period, a total of 110 purified compounds and 60 plant extracts were obtained from 112 different plants. The plants reviewed in this study belong to 70 different families reported from 36 countries around the world. The present review also discusses the drug resistance in bacteria and emphasizes the urge for new drugs
Implications of Quorum Sensing and Quorum Quenching in Aquaculture Health Management
The world human population is growing on an exponential phase and pace.
Aquaculture, raising of aquatic animals in artificial or facilitated ecosystem, is
evolving as the rapidly growing food production sector globally. The growth of
aquaculture industry has been speculated to be inevitable that may certainly
contribute toward meeting the food security of growing global population. India,
with a vast coastline and enormous marine resources, is having greater potential
to build up this industry as a productive economic sector. However, the bacterial
infections in aquaculture hatcheries and farms cause a huge loss in productivity
and remain a major challenge for the growth of this vital industry. Considering
the ill effects to environment and public health, risk of development of antibiotic
resistance, and persistence of antibiotic residues in aquaculture animal foods, it
has necessitated the regulatory bodies across the globe to restrict the usage of
antibiotics for aquaculture disease management. Hence, finding alternate
measures for the aquaculture disease management in both hatcheries and forms
is the current need. It has been well documented that exhibition of virulence
factors and formation of biofilms are the major factors for the establishment of
disease in aquaculture animals by the bacterial pathogens. Both these factors are
being regulated by quorum sensing (QS), which is a population density-dependent
expression of selected phenotypes in a coordinated manner through the production of autoinducers (AI). Quorum quenching (QQ) is a disruption of
quorum sensing. Thus, QQ is considered as one of the most preferred preventive
strategies for the ecofriendly management of aquaculture infections. The AI
molecules involved in gram-positive and gram-negative QS system and also the
enzymes and molecules involved in QQ are also widely studied in aquaculture
systems. This chapter would provide an overview of QS and QQ systems being
operated among aquaculture pathogens and other beneficial organisms in the
aquaculture system with more emphasis on shrimp aquaculture. This chapter
also emphasizes the recent developments on the impact of QS and QQ with
special reference to the virulence of bacterial pathogens both in vivo and in vitro
with a short focus on future perspectives of QQ and QS for the disease
management in aquaculture systems
Two distinct fluorescent quantum clusters of gold starting from metallic nanoparticles by pH-dependent ligand etching
Two fluorescent quantum clusters of gold, namely Au25 and Au8, have been synthesized from mercaptosuccinic acid-protected gold nanoparticles of 4-5 nm core diameter by etching with excess glutathione. While etching at pH ~3 yielded Au25, that at pH 7-8 yielded Au8. This is the first report of the synthesis of two quantum clusters starting from a single precursor. This simple method makes it possible to synthesize well-defined clusters in gram quantities. Since these clusters are highly fluorescent and are highly biocompatible due to their low metallic content, they can be used for diagnostic applications
Aurantoside K, a New Antifungal Tetramic Acid Glycoside from a Fijian Marine Sponge of the Genus Melophlus
A new tetramic acid glycoside, aurantoside K, was isolated from a marine sponge belonging to the genus Melophlus. The structure of the compound was elucidated on the basis of spectroscopic analysis (1H NMR, 1H–1H COSY, HSQC, and HMBC, as well as high-resolution ESILCMS). Aurantoside K did not show any significant activity in antimalarial, antibacterial, or HCT-116 cytotoxicity assays, but exhibited a wide spectrum of antifungal activity against wild type Candida albicans, amphotericin-resistant C. albicans, Cryptococcus neoformans, Aspergillus niger, Penicillium sp., Rhizopus sporangia and Sordaria sp
TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis
Recent studies have suggested increased plasticity of differentiated cells within the intestine to act both as intestinal stem cells (ISCs) and tumour-initiating cells. However, little is known of the processes that regulate this plasticity. Our previous work has shown that activating mutations of Kras or the NF-κB pathway can drive dedifferentiation of intestinal cells lacking Apc. To investigate this process further, we profiled both cells undergoing dedifferentiation in vitro and tumours generated from these cells in vivo by gene expression analysis. Remarkably, no clear differences were observed in the tumours; however, during dedifferentiation in vitro we found a marked upregulation of TGFβ signalling, a pathway commonly mutated in colorectal cancer (CRC). Genetic inactivation of TGFβ type 1 receptor (Tgfbr1/Alk5) enhanced the ability of KrasG12D/+ mutation to drive dedifferentiation and markedly accelerated tumourigenesis. Mechanistically this is associated with a marked activation of MAPK signalling. Tumourigenesis from differentiated compartments is potently inhibited by MEK inhibition. Taken together, we show that tumours arising in differentiated compartments will be exposed to different suppressive signals, for example, TGFβ and blockade of these makes tumourigenesis more efficient from this compartment
Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2) : a within-trial analysis of a randomised controlled trial
Background:
The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens.
Methods:
STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen). We prospectively collected direct and indirect costs and health-related quality of life data from trial participants until week 76 of follow-up. Cost-effectiveness of the oral and 6-month regimens versus control was estimated in four countries (oral regimen) and two countries (6-month regimen), using health-related quality of life for cost-utility analysis and trial efficacy for cost-effectiveness analysis. This trial is registered with ISRCTN, ISRCTN18148631.
Findings:
300 participants were included in the economic analyses (Ethiopia, 61; India, 142; Moldova, 51; Uganda, 46). In the cost-utility analysis, the oral regimen was not cost-effective in Ethiopia, India, Moldova, and Uganda from either a provider or societal perspective. In Moldova, the oral regimen was dominant from a societal perspective. In the cost-effectiveness analysis, the oral regimen was likely to be cost-effective from a provider perspective at willingness-to-pay thresholds per additional favourable outcome of more than US1900 in India, 7900 in Uganda, and from a societal perspective at thresholds of more than 3150 in India, and 1·81 to $1·00 per tablet made the oral regimen cost-effective in the provider-perspective cost-utility analysis in India and Moldova and dominate over the control regimen in the provider-perspective cost-effectiveness analysis in India.
Interpretation:
At current costs, the oral bedaquiline-containing regimen for rifampicin-resistant tuberculosis is unlikely to be cost-effective in many low-income and middle-income countries. The 6-month regimen represents a cost-effective alternative if injectable use for 2 months is acceptable.
Funding:
USAID and Janssen Research & Development
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