Chirom Aarti

Anti-tubercular peptides: A quest of future therapeutic weapon to combat tuberculosis.

Tuberculosis (TB) is a symbolic menace to mankind, infecting almost one third of the worlds populace and causing over a million mortalities annually. Mycobacterium tuberculosis (Mtb) is the key pathogen of TB that invades and replicates inside the hosts macrophage. With the emerging dilemma of multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the exigency for developing new TB drugs is an obligation now for worldwide researchers. Among the propitious antimycobacterial agents examined in last few decades, anti-tubercular peptides have been substantiated to be persuasive with multiple advantages such as low immunogenicity, selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action. In this review, we epitomized the current advances in the anti-tubercular peptides, focusing the sources and highlighting the mycobactericidal mechanisms of promising peptides. The review investigates the current anti-tubercular peptides exploited not only from human immune cells, human non-immune cells, bacteria and fungi but also from venoms, cyanobacteria, bacteriophages and several other unplumbed sources. The anti-tubercular peptides of those origins are also known to have unique second non-membrane targets within Mtb. The present context also describes the several cases that manifested the severe side effects of extant anti-TB drugs. The downfall, failure to reach clinical trial phases, inept to MDR- or XDR-TB and severe complications of the currently available anti-tubercular drugs accentuate the imperative necessity to develop efficacious drugs from adequate anti-tubercular peptides. Keeping in view of the emerging trends of drug resistant Mtb globally and unexampled mycobactericidal characteristics of peptides, the anti-tubercular peptides of varied origins can be used as a potential weapon to eradicate TB in future by developing new therapeutic drugs.

Neoteric advancement in TB drugs and an overview on the anti-tubercular role of peptides through computational approaches

Tuberculosis (TB) is a devastating threat to human health whose treatment without the emergence of drug resistant Mycobacterium tuberculosis (M. tuberculosis) is the million-dollar question at present. The pathogenesis of M. tuberculosis has been extensively studied which represents unique defence strategies by infecting macrophages. Several anti-tubercular drugs with varied mode of action and administration from diversified sources have been used for the treatment of TB that later contributed to the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). However, few of potent anti-tubercular drugs are scheduled for clinical trials status in 2017-2018. Peptides of varied origins such as human immune cells and non-immune cells, bacteria, fungi, and venoms have been widely investigated as anti-tubercular agents for the replacement of existing anti-tubercular drugs in future. In the present review, we spotlighted not only on the mechanisms of action and mode of administration of currently available anti-tubercular drugs but also the recent comprehensive report of World Health Organization (WHO) on TB epidemic, diagnosis, prevention, and treatment. The major excerpt of the study also inspects the direct contribution of different computational tools during drug designing strategies against M. tuberculosis in order to grasp the interplay between anti-tubercular peptides and targeted bacterial protein. The potentiality of some of these anti-tubercular peptides as therapeutic agents unlocks a new portal for achieving the goal of end TB strategy.

Carboxymethyl cellulase production optimization from Glutamicibacter arilaitensis strain ALA4 and its application in lignocellulosic waste biomass saccharification

Abstract In this context, carboxymethyl cellulase (CMCase) production from Glutamicibacter arilaitensis strain ALA4 was initially optimized by one factor at a time (OFAT) method using goat dung as proficient feedstock. Two-level full factorial design (25 factorial matrix) using first-order polynomial model revealed the significant (p < 0.05) influence of pH, moisture, and peptone on CMCase activity. Central composite design at N = 20 was further taken into account using a second-order polynomial equation, and thereby liberated maximum CMCase activity of 4925.56 ± 31.61 U/g in the goat dung medium of pH 8.0 and 100% moisture containing 1% (w/w) peptone, which was approximately two fold increment with respect to OFAT method. Furthermore, the partially purified CMCase exhibited stability not only at high pH and temperature but also in the presence of varied metal ions, organic solvents, surfactants, and inhibitors with pronounced residual activities. The enzymatic hydrolysis using partially purified CMCase depicted the maximum liberation of fermentable sugars from alkali pretreated lignocellulosic wastes biomass in the order of paddy straw (13.8 ± 0.15 mg/g) > pomegranate peel (9.1 ± 0.18 mg/g) > sweet lime peel (8.37 ± 0.16 mg/g), with saccharification efficiency of 62.1 ± 0.8, 40.95 ± 0.4, and 37.66 ± 0.4%, respectively after 72 hr of treatment.

Outbreak of Zika virus pathogenesis and quest of its vaccine development: Where do we stand now?

Zika virus (ZIKV) infection is a life-threatening tropical infection, mainly caused by mosquito bite. After a very long period of quietness, ZIKV infections have become a problematic issue again. Previously, the virus was limited to Africa and Asia only but later it emerged in Brazil, South America, and other parts of the world in 2015. In 2016, there are emerging new cases of sexually transmitted ZIKV infection as well. At present, there is no proper treatment and available pronounced vaccines for the treatment of ZIKV infection. The prime focal point of this review is not only to provide imperative epidemiological information on ZIKV infection in brief but also the current situation of vaccines testing on animal model as well as in clinical trial phases. Currently there is no human vaccine for this pestiferous viral infection. Therefore, prevention, proper management, and up-to-date recommendation are crucial to mitigate the possible risk of vector and non-vector transmission of ZIKV.

Enhancement of anti-tubercular activity and biomass of fermented food associated Staphylococcus hominis strain MANF2 using Taguchi orthogonal array and Box-Behnken design

The prime focus of the present investigation was to optimize statistically the anti-tubercular activity and biomass of fermented food associated Staphylococcus hominis strain MANF2 using Taguchi orthogonal array (OA) and Box-Behnken design (BBD). The anti-tubercular activity of strain MANF2 was determined against Mycobacterium tuberculosis H37Rv using luciferase reporter phase assay. Among varied media examined, the isolate exhibited impressive anti-tubercular activity with paramount relative light unit reduction of >90% in de Man Rogose Sharpe (MRS) broth. Primarily, the anti-tubercular activity and biomass of strain MANF2 were estimated in MRS broth by optimizing eight diversified parameters using one factor at a time (OFAT) method after working out a series of experiments. The most significant contributing factors selected through OFAT tool were optimized using Taguchi approach with a standard OA layout of L18 (22 × 36). Results demonstrated the significant (P ≤ 0.05) influence of pH, temperature, yeast extract, magnesium sulphate, and glycerol on response variables. These controlled variables were further optimized using BBD matrix at N = 46 by second-order polynomial equation. The fermentation medium of pH 6.5 constituting yeast extract (0.5% w/v), magnesium sulphate (0.1% w/v), and glycerol (1.5% v/v), being further incubated at 30 °C showed enhanced anti-tubercular activity (98.7%) and approximately 4 fold increment in the bacterial biomass yield (8.3 mg/mL) with respect to traditional OFAT method. Three-dimensional response plots of the quadratic model showed interdependent interaction between the significant variables. In conclusion, the present study revealed the first report on the optimization of anti-tubercular activity and biomass of S. hominis via Taguchi OA as well as BBD design, and thus, paved a path for its proficient applications in pharmaceutical industries as dynamic mycobactericidal agent in future.

Antagonistic trait of Staphylococcus succinus strain AAS2 against uropathogens and assessment of its in vitro probiotic characteristics

The desideratum aim of the present context was to isolate a promising antagonist probiotic bacterium from fermented food item as biocontrol agent against uropathogens. Among diversified isolates evaluated for antagonistic trait, Staphylococcus succinus strain AAS2 was found to be an auspicious candidate against urinary tract infection (UTI) causing bacterial pathogens, being the most active against Staphylococcus aureus with substantial activity of 352.5 ± 5.4 AU/mL. Further, the in vitro probiotic attributes of strain AAS2 were assessed using systematic methodology. The isolate exhibited tolerance to acidic condition (up to pH 3.0) and simulated gastric juice (at pH 3.0) with fairly high survival logarithmic cell counts of 5.3 ± 0.15 and 5.23 ± 0.02 log cfu/mL, respectively. Additionally, strain AAS2 showed capability to resist 0.5% w/v bile salt too. It also revealed significant values of auto-aggregation (32.5 ± 1.3-56.5 ± 1.4%) and cell surface hydrophobicity (38.35 ± 1.4%) properties. The isolate showed resistivity towards phenol (6.8 ± 0.08 log cfu/mL) and lysozyme (58.6 ± 1.6%). Further, the susceptibility trait of strain AAS2 to conventional antibiotics made this isolate a promising probiotic bacterium. Most importantly, the isolate depicted DPPH (2,2-Diphenyl-1-picrylhydrazyl) and hydroxyl radical scavenging activities in a concentration dependent manner, thereby exhibiting its propitious antioxidative properties. In a nutshell, the outcomes of this investigation divulge the plausible use of S. succinus strain AAS2 as biocontrol agent against uropathogens, and recommended further applications in pharmaceutics due to its pronounced probiotic traits.

Venom as therapeutic weapon to combat dreadful diseases of 21st century: A systematic review on cancer, TB, and HIV/AIDS

Cancer and infectious diseases are the preeminent causes of human morbidities and mortalities worldwide. At present, chemotherapy, radiotherapy, immunotherapy, and gene therapy are considered as predominant options in order to treat cancer. But these therapies provide inadequate consequences by affecting both the normal and tumor cells. On the other hand, tuberculosis (TB), and HIV (human immunodeficiency virus) infections are significant threats, causing over a million mortalities each year. The extensive applications of antibiotics have caused the microbes to acquire resistance to the existing antibiotics. With the emerging dilemma of drug resistant microbes, it has become imperative to identify novel therapeutic agents from natural sources as emphatic alternative approach. Over the past few decades, venoms derived from several reptiles, amphibians, and arthropods including snakes, scorpions, frogs, spiders, honey bees, wasps, beetles, caterpillars, ants, centipedes, and sponges have been identified as efficient therapeutics. Venoms constitute plethora of bioactive components, particularly peptides, enzymes, and other chemical entities, which exhibit a large array of anticancer and anti-pathogenic activities. This review highlights the panorama of bioactive components of animal venoms divulging the anticancer, anti-tubercular, and anti-HIV activities. In a nutshell, this context discloses the decisive role of animal venoms as alternative natural resources to combat these deadly diseases of 21st century, and propounding the plausible development of new therapeutic drugs in the present era.

In vitro investigation on probiotic, anti-Candida, and antibiofilm properties of Lactobacillus pentosus strain LAP1

OBJECTIVE To investigate the probiotic characteristics, anti-Candida activity, and antibiofilm attributes of Hentak derived Lactobacillus pentosus strain LAP1. DESIGN The probiotic properties of strain LAP1 were depicted by adapting standard protocols. The anti-Candida and antibiofilm properties of isolate were determined using agar well diffusion assay and ELISA reader test, respectively. The time-kill assay was performed using viable colony count assay. Further, the co-aggregation property of strain LAP1 was determined based on standard methodology. RESULTS Strain LAP1 exhibited not only tolerance to acidic pH but also showed resistivity (P ≤ 0.05) to simulated gastric juice exposure. Similarly, the strain was able to tolerate bile salt, showed hyperproteolytic activity, and also depicted susceptibility to most of the antibiotics tested. Auto-aggregation phenomenon (37.5-60%), hydrophobicity nature (42.85%), and survival potentiality of strain LAP1 under freeze-dried condition (9.0 ± 0.01 log CFU/ml) made the isolate a promising probiotic candidate. Cell-free neutralized supernatant (CFNS) of strain LAP1 exhibited potent antifungal activities against C. albicans, C. tropicalis, and C. krusei with arbitrary unit of 150 ± 4.34, 200 ± 5.21, and 130 ± 5.13 AU/ml, respectively and depicted remarkable reduction in the biofilm formation of respective Candida sp. in a concentration dependent manner. Moreover, time-kill assay data provided the growth inhibition of all Candida sp. in a time dependent manner. Additionally, strain LAP1 revealed significant co-aggregate percentage with C. albicans, C. tropicalis, and C. krusei. CONCLUSIONS L. pentosus strain LAP1 exhibited a good probiotic characteristics, potent anti-Candida activity, and significant antibiofilm property that could be undoubtedly recommended for its vast applications not only in food industries but also as biotherapeutic agent against Candida infections in pharmaceutical industries.

Development of Cost-effective Homemade Basal Medium for Culturing Bacillussubtilis strain KPA In Vitro

The present preliminary context was investigated to formulate a cost-effective homemade basal medium for the successful growth and subsequent culturing of Bacillus subtilis strain KPA in vitro. In view of this, PSC (Potato Soya chunk Chickpea) agar medium was prepared by adding aqueous filtered solutions of potatoes (Solanum tuberosum), soya chunks (Glycine max) and Chickpeas (Cicer arietinum) in definite proportion. This newly prepared medium favoured the growth of strain KPA and showed successful culturing after 24 h of incubation. The results observed on the agar plates were more or less similar to the growth of strain KPA on nutrient agar (NA) plates. Most importantly, the isolate grown into PSC medium showed more or less similar pattern of growth profile as in NB medium. Briefly, PSC agar medium can be used in vitro for the subsequent culturing of B. subtilis strain KPA in a cost-effective manner.