Exploring imidazo[4,5-g]quinoline-4,9-dione derivatives as Acinetobacter baumannii efflux pump inhibitor: an in silico approach.

Antimicrobial resistance (AMR) is fast becoming a medical crisis affecting the entire global population. World Health Organization (WHO) statistics show that globally 0.7 million people are dying yearly due to the emergence of AMR. By 2050, the expected number of lives lost will be 10 million per year. Acinetobacter baumannii is a dreadful nosocomial pathogen that has developed multidrug resistance (MDR) to several currently prescribed antibiotics worldwide. Overexpression of drug efflux transporters (DETs) is one of the mechanisms of multidrug resistance (MDR) in Acinetobacter baumannii. Therefore, blocking the DET can raise the efficacy of the existing antibiotics by increasing their residence time inside the bacteria. In silico screening of five synthetic compounds against three drug efflux pump from A. baumannii has identified KSA5, a novel imidazo[4,5-g]quinoline-4,9-dione derivative, to block the efflux of antibiotics. Molecular docking and simulation results showed that KSA5 could bind to adeB, adeG, and adeJ by consistently interacting with ligand-binding site residues. KSA5 has a higher binding free energy and a lower HOMO-LUMO energy gap than PAßN, suggesting a better ability to interact and inhibit DETs. Further analysis showed that KSA5 is a drug-like molecule with optimal physicochemical and ADME properties. Hence, KSA5 could be combined with antibiotics to overcome antimicrobial resistance.Communicated by Ramaswamy H. Sarma.

Identification and characterization of the novel bioactive compounds from microalgae and cyanobacteria for pharmaceutical and nutraceutical applications.

Microalgae and cyanobacteria (blue-green algae) are used as food by humans. They have gained a lot of attention in recent years because of their potential applications in biotechnology. Microalgae and cyanobacteria are good sources of many valuable compounds, including important biologically active compounds with antiviral, antibacterial, antifungal, and anticancer activities. Under optimal growth condition and stress factors, algal biomass produce varieties of potential bioactive compounds. In the current review, bioactive compounds production and their remarkable applications such as pharmaceutical and nutraceutical applications along with processes involved in identification and characterization of the novel bioactive compounds are discussed. Comprehensive knowledge about the exploration, extraction, screening, and trading of bioactive products from microalgae and cyanobacteria and their pharmaceutical and other applications will open up new avenues for drug discovery and bioprospecting.

Bacterial effluxome as a barrier against antimicrobial agents: structural biology aspects and drug targeting.

Antimicrobial resistance (AMR) is fast becoming a medical crisis affecting the entire global population. The bacterial membrane is the first layer of defense for the bacteria against antimicrobial agents (AMA), specifically transporters in the membrane efflux these AMA out of the bacteria and plays a significant role in the AMR development. Understanding the structure and the functions of these efflux transporters is essential to overcome AMR. This review discusses efflux transporters (primary, secondary, and tripartite), their domain architectures, substrate specificities, and efflux pump inhibitors (EPI). Special emphasis on nosocomial ESKAPEE (Enterococcus faecium., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli) pathogens, their multidrug efflux targets and inhibitors are discussed. Deep knowledge about the functioning of efflux pumps and their structural aspects will open up opportunities for developing new EPI, which could be used along with AMA as combination therapy to overcome the emerging AMR crisis.

Diversity of a bacterial community associated with Cliona lobata Hancock and Gelliodes pumila (Lendenfeld, 1887) sponges on the South-East coast of India.

Marine sponges are sources of various bioactive metabolites, including several anticancer drugs, produced mainly by sponge-associated microbes. Palk Bay, on the south-east coast of India, is an understudied, highly disturbed reef environment exposed to various anthropogenic and climatic stresses. In recent years, Palk Bay suffered from pollution due to the dumping of untreated domestic sewage, effluents from coastal aquaculture, tourism, salt pans, cultivation of exotic seaweeds, and geogenic heavy-metal pollution, especially arsenic, mercury, cadmium, and lead. Low microbial-abundant sponge species, such as Gelliodes pumila and Cliona lobata, were found to be ubiquitously present in this reef environment. Triplicate samples of each of these sponge species were subjected to Illumina MiSeq sequencing using V3-V4 region-specific primers. In both C. lobata and G. pumila, there was an overwhelming dominance (98 and 99%) of phylum Candidatus Saccharibacteria and Proteobacteria, respectively. The overall number of operational taxonomic units (OTUs) was 68 (40 and 13 OTUs unique to G. pumila and C. lobata, respectively; 15 shared OTUs). Alphaproteobacteria was the most abundant class in both the sponge species. Unclassified species of phylum Candidatus Saccharibacteria from C. lobata and Chelotivorans composti from G. pumila were the most abundant bacterial species. The predominance of Alphaproteobacteria also revealed the occurrence of various xenobiotic-degrading, surfactant-producing bacterial genera in both the sponge species, indirectly indicating the possible polluted reef status of Palk Bay. Studies on sponge microbiomes at various understudied geographical locations might be helpful in predicting the status of reef environments.

Revealing the impact of global mass bleaching on coral microbiome through 16S rRNA gene-based metagenomic analysis.

Coral bleaching, a phenomenon by which the expulsion of corals' alveolate endosymbiont (zooxanthellae) occurs when experiencing thermal stress is the major cause for devastation of corals. However, apart from this obligate symbiont of Scleractinian corals, there are different kinds of microbes that exist as stable, transient or sporadic members of the holobiont which reside within various microhabitats in the coral structures. Thus, this study aims to profile the coral bacterial community composition among different coral genera (thermally-sensitive (Acropora digetifera and A. noblis) and thermally resistant (Favites abdita) coral genera analyzed by field monitoring surveys) and also in a particular coral genus (thermally sensitive coral-A. digetifera) at two different sampling times (March 2016 and January 2017). A total of about 608695 paired end reads were obtained through Illumina MiSeq Sequencing platform. The alpha diversity indices (ACE, Chao1 and Shannon) were found to be higher in A. nobilis, followed by A. digetifera and Favites abdita, and the corresponding Simpson values were also found to follow the same trend, indicating that the samples are both rich in species diversity and species evenness. Proteobacteria was found to be the most dominant phylum and Gammaproteobacteria was the predominant class present in all the coral genera studied as also during different sampling time periods. As Vibrionaceae was previously reported to increase its abundance during bleaching stress conditions, bacterial profiling among different coral genera showed the presence of 86 % Vibrionaceae in A. digetifera colonies, and it was 93 % in A. digetifera samples collected during March 2016 whereas, it was found to decrease significantly (7 %) in same tagged colonies collected during January 2017. Thus, profiling of microbiome is of prime importance while studying the holobiont organism like the corals. Stress levels experienced by Palk Bay are even depicted in this microbiome study showing high alpha diversity indices that should alarm reef managers to pay attention to this precious stress tolerant reef community.