Attenuation of Las/Rhl quorum sensing regulated virulence and biofilm formation in Pseudomonas aeruginosa PAO1 by Artocarpesin.

The emergence of multidrug resistance and increased pathogenicity in microorganisms is conferred by the presence of highly synchronized cell density dependent signalling pathway known as quorum sensing (QS). The QS hierarchy is accountable for the secretion of virulence phenotypes, biofilm formation and drug resistance. Hence, targeting the QS phenomenon could be a promising strategy to counteract the bacterial virulence and drug resistance. In the present study, artocarpesin (ACN), a 6-prenylated flavone was investigated for its capability to quench the synthesis of QS regulated virulence factors. From the results, ACN showed significant inhibition of secreted virulence phenotypes such as pyocyanin (80%), rhamnolipid (79%), protease (69%), elastase (84%), alginate (88%) and biofilm formation (88%) in opportunistic pathogen, Pseudomonas aeruginosa PAO1. Further, microscopic observation of biofilm confirmed a significant reduction in biofilm matrix when P. aeruginosa PAO1 was supplemented with ACN at its sub-MIC concentration. Quantitative gene expression studies showed the promising aspects of ACN in down regulation of several QS regulatory genes associated with production of virulence phenotypes. Upon treatment with sub-MIC of ACN, the bacterial colonization in the gut of Caenorhabditis elegans was potentially reduced and the survival rate was greatly improved. The promising QS inhibition activities were further validated through in silico studies, which put an insight into the mechanism of QS inhibition. Thus, ACN could be considered as possible drug candidate targeting chronic microbial infections.

Alantolactone modulates the production of quorum sensing mediated virulence factors and biofilm formation in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen in immunocompromised patients and accounts for mortality worldwide. Quorum sensing (QS) and QS mediated biofilm formation of P. aeruginosa increase the severity of infection in the host. New and effective therapeutics are in high demand to eliminate Pseudomonas infections. The current study investigated the quorum quenching and biofilm inhibition properties of alantolactone (ATL) against P. aeruginosa PAO1. The production of key virulence factors and biofilm components were affected in bacteria when treated with sub-MIC of ATL and further validated by qRT-PCR studies. The anti-infective potential of ATL was corroborated in an in vivo model with improved survival of infected Caenorhabditis elegans and reduced bacterial colonization. In silico studies suggested the molecular interactions of ATL to QS proteins as stable. Finally, ATL was explored in the present study to inhibit QS pathways and holds the potential to develop into an effective anti-infective agent against P. aeruginosa.

Bioactive Microbial Metabolites in Cancer Therapeutics: Mining, Repurposing, and Their Molecular Targets.

The persistence and resurgence of cancer, characterized by abnormal cell growth and differentiation, continues to be a serious public health concern critically affecting public health, social life, and the global economy. Hundreds of putative drug molecules of synthetic and natural origin were approved for anticancer therapy in the last few decades. Although conventional anticancer treatment strategies have promising aspects, several factors such as their limitations, drug resistance, and side effects associated with them demand more effort in repositioning or developing novel therapeutic regimens. The rich heritage of microbial bioactive components remains instrumental in providing novel avenues for cancer therapeutics. Actinobacteria, Firmicutes, and fungi have a plethora of bioactive compounds, which received attention for their efficacy in cancer treatment targeting different pathways responsible for abnormal cell growth and differentiation. Yet the full potential remains underexplored to date, and novel compounds from such microbes are reported regularly. In addition, the advent of computational tools has further augmented the mining of microbial secondary metabolites and identifying their molecular targets in cancer cells. Furthermore, the drug-repurposing strategy has facilitated the use of approved drugs of microbial origin in regulating cancer cell growth and progression. The wide diversity of microbial compounds, different mining approaches, and multiple modes of action warrant further investigations on the current status of microbial metabolites in cancer therapeutics. Hence, in this review, we have critically discussed the untapped potential of microbial products in mitigating cancer progression. The review also summarizes the impact of drug repurposing in cancer therapy and discusses the novel avenues for future therapeutic drug development against cancer.

Sesamin and sesamolin rescues Caenorhabditis elegans from Pseudomonas aeruginosa infection through the attenuation of quorum sensing regulated virulence factors.

Pseudomonas aeruginosa is an opportunistic pathogen emerging as a public health threat owing to their multidrug resistance profiles. The quorum sensing systems of P. aeruginosa play a pivotal role in the regulation of virulence and act as the target for the development of alternative therapeutics. The study discussed about anti-quorum sensing and antibiofilm properties of lignans (sesamin and sesamolin) found in Sesamum indicum (L.) against P. aeruginosa. The effect of lignans, sesamin and sesamolin on LasR/RhlR mediated virulence factor production, biofilm formation and bacterial motility were studied. To elucidate the mechanism of action of lignans on QS pathways, QS gene expression and in depth in silico analysis were performed. Both the lignans exerted anti-quorum sensing activity at 75 µg/ml without affecting the growth of bacteria. SA and SO exhibited decreased production of virulence factors such as pyocyanin, proteases, elastase and chitinase. The important biofilm constituents of P. aeruginosa including alginate, exopolysaccharides and rhamnolipids were strongly affected by the lignans. Likewise, plausible mechanism of action of lignans were determined through the down regulation of QS regulated gene expression, molecular docking and molecular simulation studies. The in vitro analysis was supported by C. elegans infection model. SA and SO rescued pre-infected worms within 8 days of post infection and reduced the colonization of bacteria inside the intestine due to the anti-infective properties of lignans. The lignans exhibited profound action on Las pathway rather than Rhl which was elucidated through in vitro and in silico assays. In silico pharmacokinetic analysis portrayed the opportunities to employ ligands as potential therapeutics for human use. The deep insights into the anti-QS, anti-biofilm and mechanism of action of lignans can contribute to the development of novel anti-infectives against pseuodmonal infections.

Mosloflavone attenuates the quorum sensing controlled virulence phenotypes and biofilm formation in Pseudomonas aeruginosa PAO1: In vitro, in vivo and in silico approach.

Quorum sensing (QS) is the cell density dependent communication network which coordinates the production of pathogenic determinants in majority of pathogenic bacteria. Pseudomonas aeruginosa causes hospital-acquired infections by virtue of its well-defined QS network. As the QS regulatory network in P. aeruginosa regulates the virulence determinants and antibiotic resistance, attenuating the QS system seems to be influential in developing next-generation anti-infective agents. In the current study, the QS attenuation potential of a flavonoid, mosloflavone was investigated against P. aeruginosa virulence and biofilm formation. Mosloflavone inhibited the pyocyanin production, LasB elastase and chitinase by 59.52 ±â€¯2.74, 35.90 ±â€¯4.34 and 61.18 ±â€¯5.52% respectively. The QS regulated biofilm formation and development was also reduced when supplemented with sub-MIC of mosloflavone. The gene expression studies of mosloflavone using RT-PCR depicted its ability to down-regulate the expression levels of QS regulated virulence genes such as lasI (60.64%), lasR (91.70%), rhlI (57.30%), chiC (90.20%), rhlA (47.87%), rhlR (21.55%), lasB (37.80%), phzM (42.40%), toxA (61.00%), aprA (58.4%), exoS (78.01%), algD (46.60%) and pelA (50.45%). The down-regulation of QS virulence phenotypes by mosloflavone could be attributed to its binding affinity with the QS regulatory proteins, LasR and RhlR by competitively inhibiting the binding of natural autoinducers as evidenced from simulation studies. Mosloflavone also exhibited promising potential in controlling bacterial infection in Caenorhabditis elegans model system, in vivo. The anti-biofilm and anti-QS potential of mosloflavone in the current study illustrated the candidature of mosloflavone as a promising biocide.

Correction: Synthesis and antimicrobial photodynamic effect of methylene blue conjugated carbon nanotubes on E. coli and S. aureus.

Correction for 'Synthesis and antimicrobial photodynamic effect of methylene blue conjugated carbon nanotubes on E. coli and S. aureus' by Paramanantham Parasuraman et al., Photochem. Photobiol. Sci., 2019, DOI: 10.1039/c8pp00369f.

Synthesis and antimicrobial photodynamic effect of methylene blue conjugated carbon nanotubes on E. coli and S. aureus.

Catheter-related bloodstream infections (CRBSIs) are one of the leading causes of high morbidity and mortality in hospitalized patients. The proper management, prevention and treatment of CRBSIs rely on the understanding of these highly resistant bacterial infections. The emergence of such a challenge to public health has resulted in the development of an alternative antimicrobial strategy called antimicrobial photodynamic therapy (aPDT). In the presence of a photosensitizer (PS), light of the appropriate wavelength, and molecular oxygen, aPDT generates reactive oxygen species (ROS) which lead to microbial cell death and cell damage. We investigated the enhanced antibacterial and antibiofilm activities of methylene blue conjugated carbon nanotubes (MBCNTs) on biofilms of E. coli and S. aureus using a laser light source at 670 nm with radiant exposure of 58.49 J cm-2. Photodynamic inactivation in test cultures showed 4.86 and 5.55 log10 reductions in E. coli and S. aureus, respectively. Biofilm inhibition assays, cell viability assays and EPS reduction assays showed higher inhibition in S. aureus than in E. coli, suggesting that pronounced ROS generation occurred due to photodynamic therapy in S. aureus. Results from a study into the mechanism of action proved that the cell membrane is the main target for photodynamic inactivation. Comparatively higher photodynamic inactivation was observed in Gram positive bacteria due to the increased production of free radicals inside these cells. From this study, we conclude that MBCNT can be used as a promising nanocomposite for the eradication of dangerous pathogens on medical devices.

Attenuation of quorum sensing controlled virulence factors and biofilm formation in Pseudomonas aeruginosa by pentacyclic triterpenes, betulin and betulinic acid.

The production of virulence determinants and biofilm formation in numerous pathogens is regulated by the cell-density-dependent phenomenon, Quorum sensing (QS). The QS system in multidrug resistant opportunistic pathogen, P. aeruginosa constitutes of three main regulatory circuits namely Las, Rhl, and Pqs which are closely linked to its pathogenicity and establishment of chronic infections. In spite intensive antibiotic therapy, P. aeruginosa continue to be an important cause of nosocomial infections and also the major cause of mortality in Cystic Fibrosis patients with 80% of the adults suffering from chronic P. aeruginosa infection. Hence, targeting QS circuit offers an effective intervention to the ever increasing problem of drug resistant pathogens. In the present study, the pentacyclic triterpenes i.e. Betulin (BT) and Betulinic acid (BA) exhibited significant attenuation in production of QS-regulated virulence factors and biofilm formation in P. aeruginosa, at the sub-lethal concentration. The test compound remarkably interfered in initial stages of biofilm development by decreasing the exopolysaccharide production and cell surface hydrophobicity. Based on the in vivo studies, the test compounds notably enhanced the survival of Caenorhabditis elegans infected with P. aeruginosa. Furthermore, molecular docking analysis revealed that BT and BA can act as a strong competitive inhibitor for QS receptors, LasR and RhlR. The findings suggest that BT and BA can serve as potential anti-infectives in the controlling chronic infection of P. aeruginosa.

Attenuation of quorum sensing regulated virulence and biofilm development in Pseudomonas aeruginosa PAO1 by Diaporthe phaseolorum SSP12.

In recent years, Pseudomonas aeruginosa PAO1 emerged as the significant pathogenic microorganism in majority of the hospital-acquired infections due to its resistance to the conventional antibiotics by virtue of its highly organized quorum sensing and associated biofilm formation. In the present study, quorum sensing attenuation potential of Diaporthe phaseolorum SSP12 extract was investigated against P. aeruginosa PAO1 amply supported by molecular docking studies. D. phaseolorum SSP12 extract significantly inhibited the production of LasI/R mediated LasA protease, LasB elastase and chitinase with 66.52 ±â€¯5.41, 71.26 ±â€¯4.58 and 61.16 ±â€¯4.28% of inhibition respectively at a concentration of 750 µg mL-1. In addition, RhlI/R mediated production of pyocyanin, exopolysaccharides and rhamnolipids were also down-regulated by 74.71 ±â€¯3.97, 66.41 ±â€¯3.62 and 63.75 ±â€¯3.76% respectively on treatment with sub-MIC concentration of D. phaseolorum SSP12. The light, fluorescence and confocal laser scanning microscopic (CLSM) analysis confirmed the significant disruption in biofilm formation. The presence of bioactive constituents such as phenyl ethylalcohol, 2, 4-di-tert-butylphenol, fenaclon, 1, 4-phenylenediacetic acid, and benzyl hydrazine in D. phaseolorum SSP12 extract was evident from Gas chromatography-mass spectrophotometric (GC-MS) analysis. From the in silico molecular docking studies, fenaclon and 2, 4-di-tert-butylphenol competitively binds to QS receptors LasR and RhlR and alters the binding of its cognate ligands and modulates the expression of virulence phenotypes. The promising anti quorum sensing efficacy of D. phaseolorum SSP12 extract suggested new avenues for development of anti-infective drugs from fungal derived metabolites to counteract the problems associated with conventional antibiotic therapies.

Cinnamic acid attenuates quorum sensing associated virulence factors and biofilm formation in Pseudomonas aeruginosa PAO1.

OBJECTIVE: Anti-quorum sensing and anti-biofilm efficacy of Cinnamic acid against Pseudomonas aeruginosa was comparatively assessed with respect to potent quorum sensing inhibitor, Baicalein. RESULTS: At sub-lethal concentration, Cinnamic acid effectively inhibited both the production of the QS-dependent virulence factors and biofilm formation in P. aeruginosa without affecting the viability of the bacterium. The phytocompound interfered with the initial attachment of planktonic cells to the substratum thereby causing reduction in biofilm development. In addition, the in vivo study indicated that the test compound protected Caenorhabditis elegans from the virulence factors of P. aeruginosa leading to reduced mortality. The in silico analysis revealed that Cinnamic acid can act as a competitive inhibitor for the natural ligands towards the ligand binding domain of the transcriptional activators of the quorum sensing circuit in P. aeruginosa, LasR and RhlR. CONCLUSIONS: The findings suggest that Cinnamic acid may serve as a novel quorum sensing based anti-infective in controlling P. aeruginosa infections.

Evaluation of in vivo antioxidant potential of Syzygium jambos (L.) Alston and Terminalia citrina Roxb. towards oxidative stress response in Saccharomyces cerevisiae.

Excessive production and restricted elimination of free radicals like superoxide, hydroxyl radical (·OH), anion radical (O2 ·-), and non-radical hydrogen peroxide (H2O2) are related to the development of cancer, arteriosclerosis, arthritis and neurodegenerative diseases. According to a report of World Health Organisation, about 80% of the population living in the developing countries predominantly depends on the traditional medicine for their primary healthcare. Plants possess innate ability to synthesize a wide variety of enzymatic and non-enzymatic antioxidants capable of attenuating ROS-induced oxidative damage. The ethanolic leaf extracts of Syzygium jambos L. and Terminalia citrina Roxb. exhibited a significant in vitro antioxidant activity when compared with natural antioxidant, ascorbic acid. The extracts also provided strong cellular protection against the damaging effects of H2O2 induced oxidative stress in the mutant strains (tsa1Δ and sod1Δ) of Saccharomyces cerevisiae. The GC-MS analysis of the leaf extracts revealed the presence of phytoconstituents majorly constituting of terpenes, vitamin and fatty acids contributing to the antioxidant property. The plant extracts may serve as a potential source of exogenous antioxidants to combat the undesirable effects of oxidative stress.

Facile green synthesis of baicalein fabricated gold nanoparticles and their antibiofilm activity against Pseudomonas aeruginosa PAO1.

Biofilm formation is one of the major problems associated with chronic diseases and also attributes for the antibiotic resistance in bacteria. In recent times nanoparticles have been utilized to improve the efficacy of the existing antimicrobial and anti-biofilm agents. The ease in functionalization of gold nanoparticles (AuNPs) makes them a potential carrier for antimicrobial agents. However, the use of physical or chemical methods of the production of nanoparticles is expensive, labour intensive and hazardous to ecosystem. On the other hand, the use of plant based compounds serve as an eco-friendly way for the synthesis of nanoparticles with improved biocompatibility and therapeutic applicability. In the present study, phytocompound, baicalein was used as a reducing and capping agent for the synthesis of spherical shape AuNPs. The baicalein decorated gold nanoparticles (BCL-AuNPs) were characterized and evaluated for their anti-biofilm efficacy against Pseudomonas aeruginosa PAO1. The biosynthesized BCL-AuNPs was characterized using UV-Visible spectra, Dynamic Light Scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Diffraction (EDAX), and High Resolution Transmission Electron Microscopy (HR-TEM). The biosynthesized BCL-AuNPs were determined to be spherical in shape with an average size of 26.5 nm. The sub-MIC concentration of BCL-AuNPs exhibited significant anti-biofilm activity against P. aeruginosa PAO1. On treatment with BCL-AuNPs (100 g mL-1), a reduction in biofilm formation by 58.74 ± 5.8% and 76.51 ± 4.27% was observed in microtiter plate assay and tube method, respectively. A significant reduction in exopolysaccharide (EPS) production by 81.29± 2.96% was observed. The swimming and swarming motility were also effectively arrested in presence of BCL-AuNPs. Further, Light microscope and CLSM studies were carried out to examine the effect of BCL-AuNPs on the surface topography and architecture of P. aeruginosa biofilm. Thus, the present study suggests the potential use of BCL-AuNPs in the development of novel therapeutics for the prevention and treatment of biofilm associated chronic infections.

Ecofriendly biosorption of dyes and metals by bacterial biomass of Aeromonas hydrophila RC1.

The ability of dried bacterial biomass in azo dye and heavy metal removal from aqueous solution was explored. Biosorption of three textile dyes, Eriochrome black T (EBT), Acid Red 26 (AR) and Trypan blue (TB) and heavy metals (Pb and Cr) by dried biomass of Aeromonas hydrophila RC1, was investigated in a batch system under various parameters such as dye concentration, contact time, concentration of biomass, pH, and temperature. The experimental results showed that the extent of biosorption for dyes increased with increase in initial concentration of dyes, biomass concentration, contact time, temperature and decreased with increase in pH. The experimental isotherms data were analyzed using Langmuir and Freundlich isotherm equations. The Langmuir model yielded good fit to the experimental data (R² approximately 0.794, 0.844 and 0.969 for the dyes, EBT, AR and TB, respectively) with maximum monolayer adsorption capacity of 58.8 mg g⁻¹ for AR. Similarly results were obtained for heavy metals and the data fit in Langmuir model (R² value of 0.849 and 0.787) with q(m) value of 40 mg g⁻¹ for Pb. The results fit in pseudo first order kinetics with removal upto 96.67 % for Pb. Involvement of the surface characteristics of the biomass in biosorption was studied using scanning electron micrographs, FTIR, EDX and XRD analysis. Thus, use ofA. hydrophila RC1 biomass can be extensively employed in water treatment plants in order to get desired water quality in the most economical way.

Indolylmethylene benzo[h]thiazolo[2,3-b]quinazolinones: synthesis, characterization and evaluation of anticancer and antimicrobial activities.

A series of novel 10-((1H-indol-3-yl)methylene)-7-aryl-7,10-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-9(6H)-ones (8a-t) have been synthesized in good yields by the reaction of benzo[h]quinazoline-2(1H)-thiones (4a-f) with 2-chloro-N-phenylacetamide (5) followed by Knoevenagel condensation with various indole-3-carbaldehydes (7a-d) under conventional method. All the synthesized compounds were characterized by spectral studies and screened for their in vitro anticancer and antimicrobial activities. Compound 8c has exhibited excellent activity against MCF-7 (breast cancer cell line) than the standard drug Doxorubicin. Compound 8d against both the cancer cell lines, 8q against MCF-7 and 8c, 8h against HepG2 have also shown good activity. Remaining compounds have shown moderate activity against both the cell lines. Antimicrobial activity revealed that, the compound 8q and 8t against Staphylococcus aureus and 8i, 8k, 8l, 8q &8t against Klebsiella pneumoniae have shown equipotent activity on comparing with the standard drug Streptomycin. Remaining compounds have shown significant antibacterial and comparable antifungal activities against all the tested microorganisms.

Effects of gut microbiome and obesity on the development, progression and prevention of cancer (Review).

Cancer is one of the leading causes of death worldwide and it is estimated that the mortality rate of cancer will increase in the coming years. The etiology of the development and progression of cancer is multifactorial. Insights have been gained on the association between the human microbiome and tumor cell malignancy. A number of commensal microbe species are present in the human gut. They serve pivotal roles in maintaining several health and disease conditions, such as inflammatory bowel disease, irritable bowel syndrome, obesity and diabetes. Known major factors involved in cancer development include age, hormone levels, alcohol consumption, diet, being overweight, obesity, and infections, regardless of the type of cancer. Therefore, the present review aims to discuss the relationship between the gut microbiome and obesity­associated malignancies, including colorectal, gastric and liver cancer. Obesity has been reported to contribute to the development of numerous types of cancer primarily caused by high fatty food intake. In addition, obesity­associated microbiome alterations can lead to cancer and its progression. Dysbiosis of the gut microbiota can alter the metabolite profile, whilst increasing the levels of toxins, such as Bacteroides fragilis toxin and colibactin and cytolethal distending toxin, which are responsible for oncogenesis. The present review provides insights into the impact of gut microbiome dysbiosis on the progression of different types of cancers associated with obesity. It also discusses possible strategies for preserving a healthy gut microbiome. Different pre­clinical and clinical models are available for studying cancer development downstream of gut microbiome dysbiosis. Furthermore, the role of metabolites or drugs employed in colorectal, gastric and liver cancer therapy would be discussed.

Surveillance and mitigation of soil pollution through metagenomic approaches.

Soil pollution is one of the serious global threats causing risk to environment and humans. The major cause of accumulation of pollutants in soil are anthropogenic activities and some natural processes. There are several types of soil pollutants which deteriorate the quality of human life and animal health. They are recalcitrant hydrocarbon compounds, metals, antibiotics, persistent organic compounds, pesticides and different kinds of plastics. Due to the detrimental properties of pollutants present in soil on human life and ecosystem such as carcinogenic, genotoxic and mutagenic effects, alternate and effective methods to degrade the pollutants are recommended. Bioremediation is an effective and inexpensive method of biological degradation of pollutants using plants, microorganisms and fungi. With the advent of new detection methods, the identification and degradation of soil pollutants in different ecosystems were made easy. Metagenomic approaches are a boon for the identification of unculturable microorganisms and to explore the vast bioremediation potential for different pollutants. Metagenomics is a power tool to study the microbial load in polluted or contaminated land and its role in bioremediation. In addition, the negative ecosystem and health effect of pathogens, antibiotic and metal resistant genes found in the polluted area can be studied. Also, the identification of novel compounds/genes/proteins involved in the biotechnology and sustainable agriculture practices can be performed with the integration of metagenomics.

Soil carries diverse microorganisms which maintain plant and soil health.The different types of recalcitrant soil pollutants affect the ecosystem and human health.Complex pollutants can be degraded through bioremediation using microorganisms/plantsMetagenomic approaches help to explore novel organisms and enzymes involved in bioremediation.

Bioactive molecules from haloarchaea: Scope and prospects for industrial and therapeutic applications.

Marine environments and salty inland ecosystems encompass various environmental conditions, such as extremes of temperature, salinity, pH, pressure, altitude, dry conditions, and nutrient scarcity. The extremely halophilic archaea (also called haloarchaea) are a group of microorganisms requiring high salt concentrations (2-6 M NaCl) for optimal growth. Haloarchaea have different metabolic adaptations to withstand these extreme conditions. Among the adaptations, several vesicles, granules, primary and secondary metabolites are produced that are highly significant in biotechnology, such as carotenoids, halocins, enzymes, and granules of polyhydroxyalkanoates (PHAs). Among halophilic enzymes, reductases play a significant role in the textile industry and the degradation of hydrocarbon compounds. Enzymes like dehydrogenases, glycosyl hydrolases, lipases, esterases, and proteases can also be used in several industrial procedures. More recently, several studies stated that carotenoids, gas vacuoles, and liposomes produced by haloarchaea have specific applications in medicine and pharmacy. Additionally, the production of biodegradable and biocompatible polymers by haloarchaea to store carbon makes them potent candidates to be used as cell factories in the industrial production of bioplastics. Furthermore, some haloarchaeal species can synthesize nanoparticles during heavy metal detoxification, thus shedding light on a new approach to producing nanoparticles on a large scale. Recent studies also highlight that exopolysaccharides from haloarchaea can bind the SARS-CoV-2 spike protein. This review explores the potential of haloarchaea in the industry and biotechnology as cellular factories to upscale the production of diverse bioactive compounds.

Metagenomic insights into taxonomic, functional diversity and inhibitors of microbial biofilms.

Microbial cells attached to inert or living surfaces adopt biofilm mode with self-produced exopolysaccharide matrix containing polysaccharides, proteins, and extracellular DNA, for protection from adverse external stimuli. Biofilms in hospitals and industries serve as a breeding ground for drug-resistant pathogens and ARG enrichment that are linked to pathogenicity and also impede industrial production process. Biofilm formation, including virulence and pathogenicity, is regulated through quorum sensing (QS), a means of bacterial cell to cell communication for cooperative physiological processes. Hence, QS inhibition through quorum quenching (QQ) is a feasible approach to inhibit biofilm formation. In contrast, biofilms have beneficial roles in promoting plant growth, biocontrol, and wastewater treatment. Furthermore, polymicrobial biofilms can harbour novel compounds and species of industrial and pharmaceutical interest. Hence, surveillance of biofilm microbiome structure and functional attributes is crucial to determine the extent of the risk it poses and to harness its bioactive potential. One of the most preferred approaches to delineate the microbiome is culture-independent metagenomics. In this context, this review article explores the biofilm microbiome in built and natural settings such as agriculture, household appliances, wastewater treatment plants, hospitals, microplastics, and dental biofilm. We have also discussed the recent reports on discoveries of novel QS and biofilm inhibitors through conventional, metagenomics, and machine learning approaches. Finally, we present biofilm-derived novel metagenome-assembled genomes (MAGs), genomes, and taxa of medical and industrial interest.

Polymicrobial Infections and Biofilms: Clinical Significance and Eradication Strategies.

Biofilms are population of cells growing in a coordinated manner and exhibiting resistance towards hostile environments. The infections associated with biofilms are difficult to control owing to the chronicity of infections and the emergence of antibiotic resistance. Most microbial infections are contributed by polymicrobial or mixed species interactions, such as those observed in chronic wound infections, otitis media, dental caries, and cystic fibrosis. This review focuses on the polymicrobial interactions among bacterial-bacterial, bacterial-fungal, and fungal-fungal aggregations based on in vitro and in vivo models and different therapeutic interventions available for polymicrobial biofilms. Deciphering the mechanisms of polymicrobial interactions and microbial diversity in chronic infections is very helpful in anti-microbial research. Together, we have discussed the role of metagenomic approaches in studying polymicrobial biofilms. The outstanding progress made in polymicrobial research, especially the model systems and application of metagenomics for detecting, preventing, and controlling infections, are reviewed.