Nitroaromatic compounds are xenobiotics that have found multiple applications in the synthesis of foams, pharmaceuticals, pesticides, and explosives. These compounds are toxic and recalcitrant and are degraded relatively slowly in the environment by microorganisms. 2,4,6-Trinitrotoluene (TNT) is the most widely used nitroaromatic compound. Certain strains of Pseudomonas and fungi can use TNT as a nitrogen source through the removal of nitrogen as nitrite from TNT under aerobic conditions and the further reduction of the released nitrite to ammonium, which is incorporated into carbon skeletons. Phanerochaete chrysosporium and other fungi mineralize TNT under ligninolytic conditions by converting it into reduced TNT intermediates, which are excreted to the external milieu, where they are substrates for ligninolytic enzymes. Most if not all aerobic microorganisms reduce TNT to the corresponding amino derivatives via the formation of nitroso and hydroxylamine intermediates. Condensation of the latter compounds yields highly recalcitrant azoxytetranitrotoluenes. Anaerobic microorganisms can also degrade TNT through different pathways. One pathway, found in Desulfovibrio and Clostridium, involves reduction of TNT to triaminotoluene; subsequent steps are still not known. Some Clostridium species may reduce TNT to hydroxylaminodinitrotoluenes, which are then further metabolized. Another pathway has been described in Pseudomonas sp. strain JLR11 and involves nitrite release and further reduction to ammonium, with almost 85% of the N-TNT incorporated as organic N in the cells. It was recently reported that in this strain TNT can serve as a final electron acceptor in respiratory chains and that the reduction of TNT is coupled to ATP synthesis. In this review we also discuss a number of biotechnological applications of bacteria and fungi, including slurry reactors, composting, and land farming, to remove TNT from polluted soils. These treatments have been designed to achieve mineralization or reduction of TNT and immobilization of its amino derivatives on humic material. These approaches are highly efficient in removing TNT, and increasing amounts of research into the potential usefulness of phytoremediation, rhizophytoremediation, and transgenic plants with bacterial genes for TNT removal are being done.

/pdf/biological-degradation-of-2-4-6-trinitrotoluene-2fb04se8mb.pdf

Biological Degradation of 2,4,6-Trinitrotoluene

The increasing emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) in the era of human immunodeficiency virus (HIV) infection presents a major threat to effective control of TB. Drug resistance in Mycobacterium tuberculosis arises from spontaneous chromosomal mutations at low frequency. Clinical drug-resistant TB largely occurs as a result of man-made selection during disease treatment of these genetic alterations through erratic drug supply, suboptimal physician prescription and poor patient adherence. Molecular mechanisms of drug resistance have been elucidated for the major first- and second-line drugs rifampicin, isoniazid, pyrazinamide, ethambutol, the aminoglycosides and the fluoroquinolones. The relationship between drug resistance in M. tuberculosis strains and their virulence/transmissibility needs to be further investigated. Understanding the mechanisms of drug resistance in M. tuberculosis would enable the development of rapid molecular diagnostic tools and furnish possible insights into new drug development for the treatment of TB.

/pdf/mechanisms-of-drug-resistance-in-mycobacterium-tuberculosis-3n42f72bwj.pdf

Mechanisms of drug resistance in Mycobacterium tuberculosis.

Although Escherichia coli has long been recognized as the best-understood living organism, little was known about its abilities to use aromatic compounds as sole carbon and energy sources. This review gives an extensive overview of the current knowledge of the catabolism of aromatic compounds by E. coli. After giving a general overview of the aromatic compounds that E. coli strains encounter and mineralize in the different habitats that they colonize, we provide an up-to-date status report on the genes and proteins involved in the catabolism of such compounds, namely, several aromatic acids (phenylacetic acid, 3- and 4-hydroxyphenylacetic acid, phenylpropionic acid, 3-hydroxyphenylpropionic acid, and 3-hydroxycinnamic acid) and amines (phenylethylamine, tyramine, and dopamine). Other enzymatic activities acting on aromatic compounds in E. coli are also reviewed and evaluated. The review also reflects the present impact of genomic research and how the analysis of the whole E. coli genome reveals novel aromatic catabolic functions. Moreover, evolutionary considerations derived from sequence comparisons between the aromatic catabolic clusters of E. coli and homologous clusters from an increasing number of bacteria are also discussed. The recent progress in the understanding of the fundamentals that govern the degradation of aromatic compounds in E. coli makes this bacterium a very useful model system to decipher biochemical, genetic, evolutionary, and ecological aspects of the catabolism of such compounds. In the last part of the review, we discuss strategies and concepts to metabolically engineer E. coli to suit specific needs for biodegradation and biotransformation of aromatics and we provide several examples based on selected studies. Finally, conclusions derived from this review may serve as a lead for future research and applications.

http://envismadrasuniv.org/Bioremediation/pdf/Biodegradation%20of%20aromatic.pdf

Biodegradation of Aromatic Compounds by Escherichia coli

Most nitroaromatic compounds are toxic and mutagenic for living organisms, but some microorganisms have developed oxidative or reductive pathways to degrade or transform these compounds. Reductive pathways are based either on the reduction of the aromatic ring by hydride additions or on the reduction of the nitro groups to hydroxylamino and/or amino derivatives. Bacterial nitroreductases are flavoenzymes that catalyze the NAD(P)H-dependent reduction of the nitro groups on nitroaromatic and nitroheterocyclic compounds. Nitroreductases have raised a great interest due to their potential applications in bioremediation, biocatalysis, and biomedicine, especially in prodrug activation for chemotherapeutic cancer treatments. Different bacterial nitroreductases have been purified and their biochemical and kinetic parameters have been determined. The crystal structure of some nitroreductases have also been solved. However, the physiological role(s) of these enzymes remains unclear. Nitroreductase genes are widely spread within bacterial genomes, but are also found in archaea and some eukaryotic species. Although studies on regulation of nitroreductase gene expression are scarce, it seems that nitroreductase genes may be controlled by the MarRA and SoxRS regulatory systems that are involved in responses to several antibiotics and environmental chemical hazards and to specific oxidative stress conditions. This review covers the microbial distribution, types, biochemical properties, structure and regulation of the bacterial nitroreductases. The possible physiological functions and the biotechnological applications of these enzymes are also discussed.

Reduction of polynitroaromatic compounds: the bacterial nitroreductases.

In recent years, we have seen antimicrobial resistance rapidly emerge at a global scale and spread from one country to the other faster than previously thought. Superbugs and multidrug-resistant bacteria are endemic in many parts of the world. There is no question that the widespread use, overuse, and misuse of antimicrobials during the last 80 years have been associated with the explosion of antimicrobial resistance. On the other hand, the molecular pathways behind the emergence of antimicrobial resistance in bacteria were present since ancient times. Some of these mechanisms are the ancestors of current resistance determinants. Evidently, there are plenty of putative resistance genes in the environment, however, we cannot yet predict which ones would be able to be expressed as phenotypes in pathogenic bacteria and cause clinical disease. In addition, in the presence of inhibitory and sub-inhibitory concentrations of antibiotics in natural habitats, one could assume that novel resistance mechanisms will arise against antimicrobial compounds. This review presents an overview of antimicrobial resistance mechanisms, and describes how these have evolved and how they continue to emerge. As antimicrobial strategies able to bypass the development of resistance are urgently needed, a better understanding of the critical factors that contribute to the persistence and spread of antimicrobial resistance may yield innovative perspectives on the design of such new therapeutic targets.

Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence.

Nitroheterocyclic and nitroaromatic compounds constitute an enormous range of chemicals whose potent biological activity has significant human health and environmental implications. The biological activity of nitro-substituted compounds is derived from reductive metabolism of the nitro moiety, a process catalyzed by a variety of nitroreductase activities. Resistance of bacteria to nitro-substituted compounds is believed to result primarily from mutations in genes encoding oxygen-insensitive nitroreductases. We have characterized the nfsA and nfsB genes of a large number of nitrofuran-resistant mutants of Escherichia coli and have correlated mutation with cell extract nitroreductase activity. Our studies demonstrate that first-step resistance to furazolidone or nitrofurazone results from an nfsA mutation, while the increased resistance associated with second-step mutants is a consequence of an nfsB mutation. Inferences made from mutation about the structure-function relationships of NfsA and NfsB are discussed, especially with regard to the identification of flavin mononucleotide binding sites. We show that expression of plasmid-carried nfsA and nfsB genes in resistant mutants restores sensitivity to nitrofurans. Among the 20 first-step and 53 second-step mutants isolated in this study, 65 and 49%, respectively, contained insertion sequence elements in nfsA and nfsB. IS1 integrated in both genes, while IS30 and IS186 were found only in nfsA and IS2 and IS5 were observed only in nfsB. Insertion hot spots for IS30 and IS186 are indicated in nfsA, and a hot spot for IS5 insertion is evident in nfsB. We discuss potential regional and sequence-specific determinants for insertion sequence element integration in nfsA and nfsB.

Oxygen-insensitive nitroreductases: analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli.

Hantaviruses are rodent viruses that have been identified as etiologic agents of 2 diseases of humans: hemorrhagic fever with renal syndrome (HFRS) and nephropathiaepidemica (NE) in the Old World and Hantavirus pulmonary syndrome (HPS) in the New World. Orthohantavirus is a genus of sin- gle-stranded, enveloped, negative-sense RNA viruses in the family Hantaviridae of the order Bunyavi- rales. The important reservoir of Hantaviruses is rodents. Each virus serotype has its unique rodent host species and is transmitted to human beings with the aid of aerosolized virus, which is shed in urine, fae- ces and saliva and hardly by a bite of the contaminated host. Andes virus is the only Hantavirus identified to be transmitted from human-to-human and its major signs and symptoms include fever, headache, mus- cle aches, lungs filled with fluid etc. In the early 1993, this viral syndrome appeared in the Four Cor- ner location in the south western United States. The only accepted therapeutics for this virus is Ribavirin. Recently, serological examinations to identify Hantavirus antibodies have become most popular for in- vestigation among humans and rodent reservoirs.

Global Comprehensive Outlook of Hantavirus Contagion on Humans: A Review.

Study of 5-Bromo-2-Thiophene Carboxaldehyde Derived Novel Schiff Baseas a Biologically Active Agent as well as X-Ray Crystallographic Studyof C-S Coupled Benzothiazole

Schiff bases are an important class of compounds that are highly instrumental in complex formation as well as act as sensors for various metal ions. Herein, 1-aminopyrene was reacted with 5-bromo-2-thiophene carboxaldehyde to synthesize a designed Schiff base, PY-SB (N-((5-bromothiophen-2-yl) methylene) pyrene-2-amine) as a condensation product. The authenticity of the synthesized Schiff base compound was established using 1H NMR, 13C NMR, IR and HRMS techniques. Among the optoelectronic investigations, the AIEE (Aggregation Induced enhanced emission) property of PY-SB was explored and it showed 24 folds enhancement in fluorescence intensity in tetrahydrofuran (THF) and water mixtures (50:50). AIEE results were further supported by DLS (Dynamic Light scattering) study. In addition, PY-SB was found to be a highly selective and sensitive tool for the “turn-on” detection of Sn2+ ion. The turn–on fluorescence of PY-SB is due to the PET-OFF process. The electron transfer from nitrogen to the pyrene ring is completely blocked due to the formation of a complex of PY-SB with insitu generated Sn2 species(PY-SB + Sn2), which causes PET-OFF. The detection limit and binding constant of PY-SB towards Sn2+ ion were found to be 5.4 µM, and 2 × 104 M−1, respectively. The stoichiometric study through Job’s plot reveals the development of 2:1 ratio (Sn2: PY-SB) of complexation which is further confirmed by DFT, ES-MS, 1H NMR and 13C NMR, SEM-EDX. To verify the sensing behavior of PY-SB in a biological system, in vitro studies on lung adenocarcinoma cells were successfully carried out and they showed similar behavior as seen in the cuvette study. 

A novel pyrene-based Aggregation Induced Enhanced Emission active Schiff base fluorophore as a selective “turn-on” sensor for Sn2+ ions and its application in lung adenocarcinoma cells

The current article mainly highlights the mucoadhesive drug delivery with merits like the prolonged holding timeat the action site and also provides a controlled rate of drug release for improved therapeutic outcomes. Moreover, mucosal delivery can eliminate problems of the conventional oral route, such as first pass metabolism as well as acid degradation. However, the eye has unique anatomy and physiology that can cause hindrance and challenges in comparison to the other organs of the body. Additionally, conventional delivery vehicles like solutions, suspensions, and ointments have many demerits such as rapid precorneal clearance, subject variability, drainage, and uncontrolled releasefrom the dosage form. Therefore, novel pharmaceutical ophthalmic formulationslike gels, nanosuspensions, nano-particles, liposomes, microemulsions, iontophoretic dosage forms, and ocusertswere tried and tested in the past few years for ophthalmic delivery. These novel delivery products provideenhanced solubility and bioavailability in a controlled manner to overcome conventional demerits. Here in this review, we have summarized the improvement of drug studies thatare currently underway for eye drug carriers along with stages and important aspects of novel drug delivery to the eye.

N. Sandhu

Papers

Oxygen-insensitive nitroreductases: analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli.

Global Comprehensive Outlook of Hantavirus Contagion on Humans: A Review.

Study of 5-Bromo-2-Thiophene Carboxaldehyde Derived Novel Schiff Baseas a Biologically Active Agent as well as X-Ray Crystallographic Studyof C-S Coupled Benzothiazole

A novel pyrene-based Aggregation Induced Enhanced Emission active Schiff base fluorophore as a selective “turn-on” sensor for Sn2+ ions and its application in lung adenocarcinoma cells

Topical Advances in Mucoadhesive Ocular Drug Delivery System.