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With the ever-increasing population and improvement in the healthcare system in the 21st century, the incidence of chronic microbial infections and associated health disorders has also increased at a striking pace. The ability of pathogenic microorganisms to form biofilm matrix aggravates the situation due to antibiotic resistance phenomenon resulting in resistance against conventional antibiotic therapy which has become a public health concern. The canonical Quorum Sensing (QS) signaling system hierarchically regulates the expression of an array of virulence phenotypes and controls the development of biofilm dynamics. It is imperative to develop an alternative, yet effective and non-conventional therapeutic approach, popularly known as “anti-infective therapy” which seems to be interesting. In this regard, targeting microbial QS associated virulence and biofilm development proves to be a quite astonishing approach in counteracting the paucity of traditional antibiotics. A number of synthetic and natural compounds are exploited for their efficacy in combating QS associated microbial infections but the bioavailability and biocompatibility limit their widespread applications. In this context, the nanotechnological intervention offers a new paradigm for widespread biomedical applications starting from targeted drug delivery to diagnostics for the diagnosis and treatment of infectious diseases, particularly to fight against microbial infections and antibiotics resistance in biofilms. A wide range of nanomaterials ranging from metallic nanoparticles to polymeric nanoparticles and recent advances in the development of carbon-based nanomaterials such as Carbon Nanotubes (CNTs), Graphene Oxide (GO) also immensely exhibited intrinsic antiinfective properties when targeted towards microbial infections and associated MDR phenomenon. In addition, the use of nano-based platforms as carriers emphatically increases the efficacy of targeted and sitespecific delivery of potential drug candidates for preventing microbial infections.

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.

Pseudomonas aeruginosa causes severe persistent infections in immunocompromised patients by showing tolerance conventional antibiotic therapy by virtue of specialized hierarchy of quorum sensing (QS) network. The purpose of the study was to evaluate the efficacy of two Mizoram medicinal plants i.e., Anogeissus acuminata and Mallotus roxburghianus Muell. in attenuating QS regulated P. aeruginosa virulence. The crude leaf extracts were tested for their ability to combat QS associated virulence phenotypes such as pyocyanin production, LasB elastase and Staphylolytic activity and production of biofilm determinants such as alginate and exopolysaccharide in P. aeruginosa PAO1. The gas chromatography mass spectrometry (GC-MS) analysis revealed the presence of phytocompounds, the synergistic activity of which is responsible for the anti QS activity. The in silico studies provide the binding efficacy of obtained phytochemical with QS receptor protein, LasR. The in vitro studies followed by in silico analysis demonstrated the efficacy of phytochemical of A. acuminata and M. roxburghianus Muell. in competitively inhibiting the binding of natural ligand with LasR and thereby altering production of virulence phenotypes. The efficacy in down regulating bacterial virulence shown by A. acuminata and M. roxburghianus Muell. provides promising alternatives to develop next generation anti-pathogenic agents.

Pseudomonas aeruginosa is an important opportunistic pathogen which causes bacterial keratitis, cyctic fibrosis and other hospital acquired infections. Its ability to form biofilm provides resistance to conventional antibiotics and further corroborates the global health concerns. The antibiotic resistance by P. aeruginosa is due to highly complex cellular signaling system called quorum sensing (QS). As QS controls bacterial pathogenicity and plays a crucial role in biofilm formation, it is a promising alternative target to combat the bacterial virulence. The present study aims to determine the inhibitory activity of Plectranthus tenuiflorus extract on QS and biofilm development in P. aeruginosa PAO1. The crude plant extract inhibited the production of pyocyanin, elastase, protease and chitinase by 71.96 ± 1.82, 38.74 ± 1.29, 30.84 ± 1.20 and 44.75 ± 1.40 % respectively at sub-MIC concentration of 500 µg/ml. The production of biofilm aggravating phenotypes such as exopolysaccharides, alginate and rhamnolipid were also significantly reduced. The biofilm inhibition capability of P. tenuiflorus was further supported by light microscopic and confocal laser scanning microscopic analysis. The phytochemicals such as phytol and mosloflavone were identified from the crude extract using gas chromatography–mass spectrometry (GC-MS). The role of these phytochemicals in down regulation of QS in P. aeruginosa was further confirmed by in silico studies targeting transcriptional receptors, LasR and RhlR of the QS regulatory network. The in vitro and docking studies suggest the anti QS potential of P. tenuiflorus in combating the bacterial pathogenesis.

The encapsulation of cinnamaldehyde into biodegradable polymeric systems represents a possible strategy to overcome the bioavailability issues and enhance the sustained release of the drug at the target sites. In the present study, the efficacy of cinnamaldehyde encapsulated chitosan nanoparticles (CANPs) in attenuating the quorum sensing (QS) regulated virulence of P. aeruginosa PAO1 was investigated. CANPs were synthesized by ionic gelation method, characterized by dynamic light scattering (DLS), and transmission electron microscopic (TEM) analysis. The DLS and TEM analysis confirmed the synthesis of CANPs with a mean diameter of 208.12 nm. The encapsulation efficiency was observed to be 65.04 ± 3.14% and in vitro release study confirmed the slow and sustained release of cinnamaldehyde. CANPs showed significant anti quorum sensing activity by down regulating the QS regulated virulence factors and associated biofilm formation as evidenced from microscopic observation. CANPs also significantly altered the swimming and swarming motility of P. aeruginosa PAO1. The present results suggested the greater prospective of the application of CANPs as potential anti quorum sensing agents as compared to native cinnamaldehyde and suggested new avenues for development of novel anti-infective agents in the post antibiotic era.

From ancient times, plants and plant derived products are exploited as a prominent source of folkloric medicines with tremendous therapeutic potential for an array of health disorders. In the present study, ethanolic leaf extract of Hibiscus sabdariffa and Croton caudatus were evaluated for free radical scavenging activity in Saccharomyces cerevisiae model system. H. sabdariffa and C. caudatus showed tremendous DPPH free radical scavenging potential with an IC50 value of 184.88 and 305.39 µg/mL respectively at a concentration of 500 µg/mL. The ethanolic leaf extract of H. sabdariffa and C. caudatus also showed significant hydoxyl radical scavenging and total antioxidant activity. Ascorbic acid was used as positive control. The in vitro antioxidant activity was further supported by in vivo studies using radical scavenging mechanism in S. cerevisiae wild type and its isogenic deletion strains sod1∆ and tsa1∆. The mutant yeast cells substantially scavenged the stress generated by H2O2 when supplemented with ethanolic leaf extract of H. sabdariffa and C. caudatus as evident from spot assays followed by fluorescence assay (DCF-DA) using fluorescence microscopic and intensity studies. H. sabdariffa and C.caudatus significantly neutralize the ROS level in yeast mutants with concomitant decrease in fluorescence intensity as compared to the untreated yeast cells. The results suggested the efficacy of H. sabdariffa and C. caudatus as potent antioxidants in yeast system and thus their futuristic applications in therapeutics.

Over the last few decades, though there is a significant upliftment in the technological interfaces and advancement in the biotechnological and biomedical sectors to combat microbial infections, the increasing prevalence of multidrug resistance (MDR) to conventional antimicrobials remains a serious public health issue. The inherent ability of pathogenic bacteria to form highly resistant biofilm matrix further aggravates the situation emphatically. In this context, the current drug discovery programmes focus on the development of novel bioactive compounds to combat bacterial virulence and biofilm formation. Though the natural bioactive compounds exhibit characteristic influence on biofilm development, their solubility, bioavailability and biocompatibility limit their widespread application. In this regard, nanotechnological intervention has revolutionized the current drug discovery programmes to combat microbial infections and associated health consequences. Among the different nanomaterials used, nanoemulsions hold unique advantages to be used as novel antimicrobials and anti-biofilm agents owing to their unique physicochemical properties, improved stability and enhanced biocompatibility. Nanoemulsions are nano-sized emulsions, engineered and designed to characteristically improve the targeted and localized delivery of drug moieties or bioactive compounds in the physiological conditions with prolonged therapeutic efficacy without any adverse effect and related toxicity. Owing to the physical stability and improved bioavailability of nanoemulsions, it can be exploited for efficient and localized delivery of antimicrobial drugs and anti-biofilm agents to target sites for combating microbial infections, biofilm formation and associated MDR phenomenon. The antimicrobial nanoemulsions have also exhibited widespread application in the pharmaceutical and food processing industries and agricultural sectors suggesting new avenues and dimensions for the development of novel antimicrobials in the post-antibiotic era.

Pink pigmented facultative methylotrophs (PPFMs) are diversified group of microorganisms that promote plant growth by producing indole acetic acid (IAA) and cytokinins. The objective of the present study is to isolate and characterize methylotrophic bacteria from the phyllosphere of mustard plant (Brassica niagra) and to study their plant growth promotion in tomato (Lycopersicon esculentum L.). Bacteria were isolated from the phyllosphere and the conserved mxaF gene sequence was amplified. Production of IAA was determined by High Performance Thin Layer Chromatography (HPTLC) and further quantified by spectrophotometric analysis. Effect of seed bacterization with the bacterial isolate MM2 was studied for percentage seed germination, root & shoot length. Based on NCBI BLAST search of the mxaF sequence obtained, the bacterial isolate was identified as Methylobacterium extorquens MM2. The amount of IAA produced by M. extorquens MM2 was 6.16 μg/ml. M. extorquens MM2 significantly increased seed vigour index (SVI) in tomato plants. The SVI of the treated plant was 1462.56 ± 83.96 as compared to the control, 1019.94 ± 113.61. Foliar application of M. extorquens MM2 also contributed a substantial impact on growth of tomato plant. The bacterial isolate M. extorquens MM2 thus can be employed in the crops for sustainable agriculture.