Marine bioactive compounds as antibiofilm agent: a metabolomic approach.

The ocean is a treasure trove of both living and nonliving creatures, harboring incredibly diverse group of organisms. A plethora of marine sourced bioactive compounds are discovered over the past few decades, many of which are found to show antibiofilm activity. These are of immense clinical significance since the formation of microbial biofilm is associated with the development of high antibiotic resistance. Biofilms are also responsible to bring about problems associated with industries. In fact, the toilets and wash-basins also show degradation due to development of biofilm on their surfaces. Antimicrobial resistance exhibited by the biofilm can be a potent threat not only for the health care unit along with industries and daily utilities. Various recent studies have shown that the marine members of various kingdom are capable of producing antibiofilm compounds. Many such compounds are with unique structural features and metabolomics approaches are essential to study such large sets of metabolites. Associating holobiome metabolomics with analysis of their chemical attribute may bring new insights on their antibiofilm effect and their applicability as a substitute for conventional antibiotics. The application of computer-aided drug design/discovery (CADD) techniques including neural network approaches and structured-based virtual screening, ligand-based virtual screening in combination with experimental validation techniques may help in the identification of these molecules and evaluation of their drug like properties.

Regulation of ß-amylase synthesis: a brief overview.

BACKGROUND: The major activity of ß-amylase (BMY) is the production of maltose by the hydrolytic degradation of starch. BMY is found to be produced by some plants and few microorganisms only. The industrial importance of the enzyme warrants its application in a larger scale with the help of genetic engineering, for which the regulatory mechanism is to be clearly understood. RESULTS AND CONCLUSION: In plants, the activities of BMY are regulated by various environmental stimuli including stress of drought, cold and heat. In vascular plant, Arabidopsis sp. the enzyme is coded by nine BAM genes, whereas in most bacteria, BMY enzymes are coded by the spoII gene family. The activities of these genes are in turn controlled by various compounds. Production and inhibition of the microbial BMY is regulated by the activation and inactivation of various BAM genes. Various types of transcriptional regulators associated with the plant- BMYs regulate the production of BMY enzyme. The enhancement in the expression of such genes reflects evolutionary significance. Bacterial genes, on the other hand, as exemplified by Bacillus sp and Clostridium sp, clearly depict the importance of a single regulatory gene, the absence or mutation of which totally abolishes the BMY activity.

Bacterial Cellulose: Production, Characterization, and Application as Antimicrobial Agent.

Bacterial cellulose (BC) is recognized as a multifaceted, versatile biomaterial with abundant applications. Groups of microorganisms such as bacteria are accountable for BC synthesis through static or agitated fermentation processes in the presence of competent media. In comparison to static cultivation, agitated cultivation provides the maximum yield of the BC. A pure cellulose BC can positively interact with hydrophilic or hydrophobic biopolymers while being used in the biomedical domain. From the last two decades, the reinforcement of biopolymer-based biocomposites and its applicability with BC have increased in the research field. The harmony of hydrophobic biopolymers can be reduced due to the high moisture content of BC in comparison to hydrophilic biopolymers. Mechanical properties are the important parameters not only in producing green composite but also in dealing with tissue engineering, medical implants, and biofilm. The wide requisition of BC in medical as well as industrial fields has warranted the scaling up of the production of BC with added economy. This review provides a detailed overview of the production and properties of BC and several parameters affecting the production of BC and its biocomposites, elucidating their antimicrobial and antibiofilm efficacy with an insight to highlight their therapeutic potential.

Bio characterization of purified isoamylase from Rhizopus oryzae.

Extracellular isoamylase produced by Rhizopus oryzae PR7 MTCC 9642 in in Erlenmeyer flasks was purified by ultrafiltration and by two steps of Superose 6 C-10/300GL gel chromatography. The enzyme molecule was found to be a monomer with molecular weight of 68 kDa.The purified isoamylase showed optimum activity at pH 5.5 and temperature 55 °C. The catalytic activity was found to remain stable at a broad range of pH (4-8) and could show remarkable thermo resistance specially in presence of exogenous thiols. The noteworthy enhancement of activity in presence of Mn2+ indicated its role as enzyme cofactor while thermos and chemostability in presence of exogenous thiols indicated the presence of disulfide linkage at active site of the enzyme. Both in vitro study and doking analysis indicated the highest affinity of the isoamylase of R. oryzae PR7 toward glycogen and the enzyme exhibited Km and Vmax values of 0.38 mg/mL and 6.65 mM/min/mL, respectively. Purified debranching amylolytic enzyme from R. oryzae PR7 has potential for the study of glycogen and starch structure and industrial application in combination with other amylolytic enzymes. The rapid, convenient, relatively simple purification process and other functional attributes of the enzyme made it competent to be employed for industrial utilization.

Role of Virus on Oral Biofilm: Inducer or Eradicator?

Sessile forms of bacteria remain as an aggregation on biotic and abiotic surfaces, known as biofilm, that protects them from various environmental stress, like antibiotic and host immune response. The oral cavity is enriched with microbial biofilm, formed on dental surface, gingival plaques, and associated tissue. Several pathogenic viruses enter the oral cavity and form biofilms either on pre-existing biofilms or on cell surfaces. They achieved persistence and the ability to prompt dissemination in the biofilm. Dental biofilms of COVID-19 patients are found to harbor SARS-CoV-2 RNA and may act as a budding reservoir, which also promotes COVID-19 transmission. On the other hand, most of the prokaryotic viruses or bacteriophages essentially kill the host bacteria and thereby destroy the biofilm. Bacteria try to evade from phage attack by concealing in biofilm, whereas the eukaryotic virus often utilize bacterial biofilm to escape host's immune response and to achieve an easy way of dissemination. The opposite action of viruses as an inducer and eradicator of biofilm has made the oral biofilm a unique ecosystem.

Docking assisted mechanistic elucidation of bio conversion of hexavalent chromium by Serratia marcescens AJRR-22 that is effective yet long term sustainable in bio-geosphere.

Environmental accumulation of hexavalent chromium [Cr(VI)] in the food chain can induce detrimental effects on plants and animals, which calls for effective remediation strategies using biological entities. The bacterium isolated from an iron mine in Odisha, India, is identified asSerratia marcescensAJRR-22. This multi-metal tolerant strain is capable of bio-converting up to 350 mg/L Cr(VI) within 72 h of incubation. Observable electron dense precipitates in transmission electron microscopic images, data patterns in fluorescence microscopy and flow cytometry clearly reveal the chromate reduction ability of the strain. The molecular study is depicted by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopic analyses. Furthermore, a simulation study to estimate the interactions of chromium bound flavin reductasewith predicted docked complexes suggests significant negative Gibbs free energy and a low inhibition constant (Ki), signifying strong spontaneous binding of Cr(VI) to the enzyme, which makes the strain an efficient candidate for chromium bioremediation.

Immobilised antimicrobial peptides in downregulation of biofilm.

Colonisation of sessile bacterial species on biotic and abiotic surfaces is responsible for the development of various infections in humans. At present, biofilm-associated chronic infections have been a prime concern among the healthcare practitioners since they are impermeable to drugs, resulting in the development of antibiotic resistance or multi-drug resistance. For a few decades, a lot of research activity has been performed in the development of alternative therapeutics to combat biofilm-associated chronic infections. The presence of extracellular polymeric substance (EPS) prevents the permeation of most of the drugs rendering drug failures. The use of small molecules has been necessary to penetrate easily through the EPS and act on the targeted cells. In present days, the use of antimicrobial peptides (AMPs) has gained immense importance as alternative therapeutics since they exhibit a novel class of antibiotics exhibiting a wide spectrum of activity and possess a low rate of development of resistance. In the last few decades, a large number of AMPs have been identified from varied groups of organisms as effector molecules for innate immune system acting as an important line of defence. In this review, we will discuss the use of AMPs as effective agents to combat various biofilm-associated chronic infections.

Periodontitis: An Oral Disease with Severe Consequences.

Periodontitis, being a multifactorial disorder is found to be the most common oral disease denoted by the inflammation of gingiva and resorption of tooth supporting alveolar bone. The disease being closely linked with fast life style and determined by unhygienic behavioural factors, the internal milieu of oral cavity and formation of plaque biofilm on the dental and gingival surfaces. Porphyromonas gingivalis, being the major keystone pathogen of the periodontal biofilm evokes host immune responses that causes damage of gingival tissues and resorption of bones. The biofilm associated microbial community progressively aggravates the condition resulting in chronic inflammation and finally tooth loss. The disease often maintains bidirectional relationship with different systemic, genetic, autoimmune, immunodeficiency diseases and even psychological disorders. The disease can be diagnosed and predicted by various genetic, radiographic and computer-aided design (CAD) & computer-aided engineering (CAE) and artificial neural network (ANN). The elucidation of genetic background explains the inheritance of the disease. The therapeutic approaches commonly followed include mechanical removal of dental plaque with the use of systemic antibiotics. Awareness generation amongst local people, adoption of good practice of timely tooth brushing preferably with fluoride paste or with nanoconjugate pastes will reduce the chance of periodontal plaque formation. Modern tissue engineering technology like 3D bioprinting of periodontal tissue may help in patient specific flawless regeneration of tooth structures and associated bones.

Analysis of Antibiofilm Activities of Bioactive Compounds from Honeyweed (Leonurus sibiricus) Against P. aeruginosa: an In Vitro and In Silico Approach.

Leonurus sibiricus (Red verticilla, honeyweed) is a type of herbaceous plant predominantly found in Asian subcontinents as weed in crop fields and is widely used for treating diabetes, bronchitis, and menstrual irregularities. However, there is a dearth of study in the application of the plant phytocompounds for treating biofilm-associated chronic infections. The bioactive compounds mainly comprise of tri-terpenes, di-terpenes, phenolic acid, and flavonoids which may have potential role as antimicrobial and antibiofilm agents. Acute and chronic infection causing microbes usually form biofilm and develop virulence factors and antibiotic resistance through quorum sensing (QS). In this study, the bioactive compounds leosibirin, sibiricinone A, leosibirone A, leonotin, quercetin, lavandulifolioside, and myricetin were identified using GC-MS analysis. These were used for analyzing the antibiofilm and anti-quorum sensing activities (rhamnolipid, AHL assay, swarming motility assay) against the biofilm formed by Pseudomonas aeruginosa, the most significant nosocomial disease-causing bacteria. The compounds were able to bring about maximum inhibition in biofilm formation and QS. Although the antibiofilm activity of the phytoextract was found to be higher than that of individual phytocompounds at a concentration of 250 µg/mL, quercetin and myricetin showed highest antibiofilm activity against Pseudomonas aeruginosa, respectively, at MIC values of 135 µg/mL and 150 µg/mL against P aeruginosa. FT-IR study also revealed that the active ingredients were able to bring about the destruction of exopolysaccharides (EPS). These observations were further validated by molecular docking interactions that showed the active ingredients inhibit the functioning of QS sensing proteins by binding with them. It was observed that myricetin showed better interactions with the QS proteins of P. aeruginosa. Myricetin and quercetin show considerable inhibition of biofilm in comparison to the phytocompounds. Thus, the present study suggests that the active compounds from L. sibiricus can be used as an alternate strategy in inhibiting the biofilm formed by pathogenic organisms.

Purification, Characterization, and Application of Endoglucanase from Rhizopus oryzae as Antibiofilm Agent.

The enzyme endoglucanase is responsible for the depolymerization of cellulose. This study focuses on characterization and purification of endoglucanase from Rhizopus oryzae MTCC 9642 through a simple size exclusion method and its effective application as an antibiofilm agent. Extracellular ß-1,4-endoglucanase, an enzyme that catalyzes the hydrolysis of carboxymethyl cellulose, was found to be synthesized by Rhizopus oryzae MTCC 9642. The enzyme was purified up to homogeneity simply by size exclusion process through ultrafiltration and gel chromatography. The molecular weight of purified enzyme protein was estimated to be 39.8 kDa and it showed the highest substrate affinity towards carboxymethyl-cellulose with Km and Vmax values of 0.833 mg ml-1 and of 0.33 mmol glucose min-1 mg-1protein, respectively. The purified enzyme exhibited optimal activity at pH 6 with a broad stability range of pH 3-8. The most preferred temperature was 35 °C and 50% of activity could be retained after the thermal exposure at 40 °C for 25 min. The purified enzyme protein was inactivated by Cu2+, while the activity could be enhanced by the addition of exogenous thiols. Since biofilm is a challenge for health sector, with the aim of eradicating the biofilm, the purified endoglucanase was used to remove biofilm produced by two nosocomial bacteria. As predicted by in silico molecular docking interaction, the purified enzyme could effectively degrade biofilm architecture of bacterial strains S. aureus and P. aeruginosa by 76.52 ± 6.52% and 61.67 ± 8.76%, respectively. The properties of purified enzyme protein, as elucidated by in vitro and in silico characterization, may be favourable for its commercial applications as a potent antibiofilm agent.

Biogenic silver nanoparticles (AgNPs) from Tinosporacordifolia leaves: An effective antibiofilm agent against Staphylococcus aureus ATCC 23235.

Medicinal plants are long known for their therapeutic applications. Tinospora cordifolia (commonly called gulancha or heart-leaved moonseed plant), a herbaceous creeper widely has been found to have antimicrobial, anti-inflammatory, anti-diabetic, and anti-cancer properties. However, there remains a dearth of reports regarding its antibiofilm activities. In the present study, the anti-biofilm activities of phytoextractof T. cordifolia and the silver nanoparticles made from this phytoextract were tested against the biofilm of S.taphylococcus aureus, one of the major nosocomial infection-producing bacteria taking tetracycline antibiotic as control. Both phytoextract from the leaves of T. cordifolia, and the biogenic AgNPs from the leaf extract of T. cordifolia, were found successful in reducing the biofilm of Staphylococcus aureus. The biogenic AgNPs formed were characterized by UV- Vis spectroscopy, Field emission Scanning Electron Microscopy (FE- SEM), and Dynamic light scattering (DLS) technique. FE- SEM images showed that the AgNPs were of size ranging between 30 and 50 nm and were stable in nature, as depicted by the zeta potential analyzer. MIC values for phytoextract and AgNPs were found to be 180 mg/mL and 150 µg/mL against S. aureusrespectively. The antibiofilm properties of the AgNPs and phytoextract were analyzed using the CV assay and MTT assay for determining the reduction of biofilms. Reduction in viability count and revival of the S. aureus ATCC 23235 biofilm cells were analyzed followed by the enfeeblement of the EPS matrix to quantify the reduction in the contents of carbohydrates, proteins and eDNA. The SEM analyses clearly indicated that although the phytoextracts could destroy the biofilm network of S. aureuscells yet the biogenicallysynthesizedAgNPs were more effective in biofilm disruption. Fourier Transformed Infrared Radiations (FT- IR) analyses revealed that the AgNPs could bring about more exopolysaccharide (EPS) destruction in comparison to the phytoextract. The antibiofilm activities of AgNPs made from the phytoextract were found to be much more effective than the non-conjugated phytoextract, indicating the future prospect of using such particles for combatting biofilm-mediated infections caused by S aureus.

Light and scanning electron microscopic studies on chromium-induced anemia in a murine model.

Blood hemoglobin level, hematocrit value and erythrocyte count were reduced by 17.5, 17.4 and 15.9%, respectively, as compared to the controls, in Swiss mice treated intraperitoneally with hexavalent chromium (4 mg of potassium dichromate per Kg for 5 day per week) for 2 weeks. Echinocytic transformation of 33.8% erythrocytes, as revealed by both light and scanning electron microscopy, indicated the anemia to be hemolytic in nature. Leucopenia was apparent after 2 weeks (mean leucocyte count: 4.91 thousand c mm(-1)), but not 1 week of treatment (mean count: 6.43 thousand c mm(-1)), However, cytochemical studies indicated that chromium did not interfere with iron utilization for hemoglobin synthesis and also, did not cause denaturation of already synthesized hemoglobin. The study hints to the necessity of periodic monitoring of blood in workers of chromium-dependent tanneries of Kolkata, India.

Effect of Extracellular Factors on Growth and Dimorphism of Rhizopus oryzae with Multiple Enzyme Synthesizing Ability.

Rhizopus oryzae PR7 MTCC 9642 was a dimorphic fungus that showed a regular 90 days cycle of filament (mycelium) to pellet (yeast) transformation through a distinct bottom dwelling intermediate state and the pellets never revert back to filamentous form. Apart from the normal cycle, high temperature (37°C and above) and extreme pH also induced the yeast formation. Among the ions tested, calcium and chloride ions were found to restore the filamentous morphology, even in extreme pH and temperature. Cysteine HCl also played noteworthy role in maintaining mycelial growth even at adverse condition. Immobilized spores showed the appearance of intermediate form instead of typical yeast form even at high temperature. The strain could produce a number of extracellular hydrolytic enzymes like cellulolytic, xylanolytic, pectinolytic and amylolytic enzymes. The pellet and mycelial forms were found to be a better producer of cellulase-lignocellulase enzymes and amylolytic enzymes respectively, which might be correlated with their infectivity. Increase in inoculum size, agitation during cultivation, change in carbon and nitrogen source failed to induce mycelial growth in extreme conditions, which might be explained as irreversible change of configuration of protein responsible for mycelial development.

Citrus Essential Oils: a Treasure Trove of Antibiofilm Agent.

Biofilms are groups of adherent cell communities that cohere to the biotic and abiotic surfaces with the help of extracellular polymeric substances (EPS). EPS allow bacteria to form a biofilm that facilitates their binding to biotic and abiotic surfaces and provides resistance to the host immune responses and to antibiotics. There are efforts that have led to the development of natural compounds that can overcome this biofilm-mediated resistance. Essential oils (EOs) are a unique mixture of compounds that plays a key role in preventing the development of biofilm. The present overview focusses on the role of various types of citrus essential oils in acting against the biofilm, and the antibiofilm properties of natural compounds that may show an avenue to treat the multidrug-resistant bacteria.

Immobilized enzymes as potent antibiofilm agent.

Biofilm has been a point of concern in hospitals and various industries. They not only cause various chronic infections but are also responsible for the degradation of various medical appliances. Since the last decade, various alternate strategies are being adopted to combat the biofilm formed on various biotic and abiotic surfaces. The use of enzymes as a potent anti-fouling agent is proved to be of utmost importance as the enzymes can inhibit biofilm formation in an eco-friendly and cost-effective way. The physical and chemical immobilization of the enzyme not only leads to the improvement of thermostability and reusability of the enzyme, but also gains better efficiency of biofilm removal. Immobilization of amylase, cellobiohydrolase, pectinase, subtilisin A and ß-N-acetyl-glucosaminidase (DspB) are proved to be most effective in inhibition of biofilm formation and removal of matured biofilm than their free forms. Hence, these immobilized enzymes provide greater eradication of biofilm formed on various surfaces and are coming up to be the potent antibiofilm agent.

Engineered Biofilm: Innovative Nextgen Strategy for Quality Enhancement of Fermented Foods.

Microbial communities within fermented food (beers, wines, distillates, meats, fishes, cheeses, breads) products remain within biofilm and are embedded in a complex extracellular polymeric matrix that provides favorable growth conditions to the indwelling species. Biofilm acts as the best ecological niche for the residing microbes by providing food ingredients that interact with the fermenting microorganisms' metabolites to boost their growth. This leads to the alterations in the biochemical and nutritional quality of the fermented food ingredients compared to the initial ingredients in terms of antioxidants, peptides, organoleptic and probiotic properties, and antimicrobial activity. Microbes within the biofilm have altered genetic expression that may lead to novel biochemical pathways influencing their chemical and organoleptic properties related to consumer acceptability. Although microbial biofilms have always been linked to pathogenicity owing to its enhanced antimicrobial resistance, biofilm could be favorable for the production of amino acids like l-proline and L-threonine by engineered bacteria. The unique characteristics of many traditional fermented foods are attributed by the biofilm formed by lactic acid bacteria and yeast and often, multispecies biofilm can be successfully used for repeated-batch fermentation. The present review will shed light on current research related to the role of biofilm in the fermentation process with special reference to the recent applications of NGS/WGS/omics for the improved biofilm forming ability of the genetically engineered and biotechnologically modified microorganisms to bring about the amelioration of the quality of fermented food.

Precision targeting of food biofilm-forming genes by microbial scissors: CRISPR-Cas as an effective modulator.

The abrupt emergence of antimicrobial resistant (AMR) bacterial strains has been recognized as one of the biggest public health threats affecting the human race and food processing industries. One of the causes for the emergence of AMR is the ability of the microorganisms to form biofilm as a defense strategy that restricts the penetration of antimicrobial agents into bacterial cells. About 80% of human diseases are caused by biofilm-associated sessile microbes. Bacterial biofilm formation involves a cascade of genes that are regulated via the mechanism of quorum sensing (QS) and signaling pathways that control the production of the extracellular polymeric matrix (EPS), responsible for the three-dimensional architecture of the biofilm. Another defense strategy utilized commonly by various bacteria includes clustered regularly interspaced short palindromic repeats interference (CRISPRi) system that prevents the bacterial cell from viral invasion. Since multigenic signaling pathways and controlling systems are involved in each and every step of biofilm formation, the CRISPRi system can be adopted as an effective strategy to target the genomic system involved in biofilm formation. Overall, this technology enables site-specific integration of genes into the host enabling the development of paratransgenic control strategies to interfere with pathogenic bacterial strains. CRISPR-RNA-guided Cas9 endonuclease, being a promising genome editing tool, can be effectively programmed to re-sensitize the bacteria by targeting AMR-encoding plasmid genes involved in biofilm formation and virulence to revert bacterial resistance to antibiotics. CRISPRi-facilitated silencing of genes encoding regulatory proteins associated with biofilm production is considered by researchers as a dependable approach for editing gene networks in various biofilm-forming bacteria either by inactivating biofilm-forming genes or by integrating genes corresponding to antibiotic resistance or fluorescent markers into the host genome for better analysis of its functions both in vitro and in vivo or by editing genes to stop the secretion of toxins as harmful metabolites in food industries, thereby upgrading the human health status.

Lactic Acid Bacteria (LAB): Autochthonous and Probiotic Microbes for Meat Preservation and Fortification.

The enhanced concern of the consumers regarding the safety, quality of the food products, and avoidance of the use of chemical food preservatives has resulted in a breakthrough in biopreservation. This has resulted in the use of beneficial microbial species, including bacteria and their secondary metabolites, to enhance the shelf-life and quality of the food products. Meat preservation and fortification are among the biggest concerns, as they are relevant to the majority of food products. The chemical preservatives conventionally used in preserving meat and meat products possess several detrimental effects on the consumers. Thus, alternative strategies are needed to combat strategically in facilitating the shelf-life and quality. Lactic acid bacteria (LAB) are considered the safest organism and have a profound role in food and food-processing industries. The biofilm developed by the bacteria prevents the growth of various undesirable microorganisms on meat and meat products. Various studies depicted that LAB produces various antimicrobial metabolites that can act effectively on the food-degrading pathogens, rendering it safe and enhancing shelf-life. This review, thus, deals with the use of LAB as biopreservatives for enhancing the shelf-life of meat and meat products and helping its fortification.

Seafood Discards: A Potent Source of Enzymes and Biomacromolecules With Nutritional and Nutraceutical Significance.

In recent times, the seafood industry is found to produce large volumes of waste products comprising shrimp shells, fish bones, fins, skins, intestines, and carcasses, along with the voluminous quantity of wastewater effluents. These seafood industry effluents contain large quantities of lipids, amino acids, proteins, polyunsaturated fatty acids, minerals, and carotenoids mixed with the garbage. This debris not only causes a huge wastage of various nutrients but also roots in severe environmental contamination. Hence, the problem of such seafood industry run-offs needs to be immediately managed with a commercial outlook. Microbiological treatment may lead to the valorization of seafood wastes, the trove of several useful compounds into value-added materials like enzymes, such as lipase, protease, chitinase, hyaluronidase, phosphatase, etc., and organic compounds like bioactive peptides, collagen, gelatin, chitosan, and mineral-based nutraceuticals. Such bioconversion in combination with a bio-refinery strategy possesses the potential for environment-friendly and inexpensive management of discards generated from seafood, which can sustainably maintain the production of seafood. The compounds that are being produced may act as nutritional sources or as nutraceuticals, foods with medicinal value. Determining utilization of seafood discard not only reduces the obnoxious deposition of waste but adds economy in the production of food with nutritional and medicinal importance, and, thereby meets up the long-lasting global demand of making nutrients and nutraceuticals available at a nominal cost.

Phytocompound Mediated Blockage of Quorum Sensing Cascade in ESKAPE Pathogens.

Increased resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. (ESKAPE) pathogens against various drugs has enhanced the urge for the development of alternate therapeutics. Quorum sensing (QS) is a density dependent cell-to-cell communication mechanism responsible for controlling pathogenicity with the regulation of gene expression. Thus, QS is considered a potential target for the development of newer anti-biofilm agents that do not depend on the utilization of antibiotics. Compounds with anti-QS effects are known as QS inhibitors (QSIs), and they can inhibit the QS mechanism that forms the major form in the development of bacterial pathogenesis. A diverse array of natural compounds provides a plethora of anti-QS effects. Over recent years, these natural compounds have gained importance as new strategies for combating the ESKAPE pathogens and inhibiting the genes involved in QS. Different pharmacognostical and pharmacological studies have been carried out so far for identification of novel drugs or for the discovery of their unique structures that may help in developing more effective anti-biofilm therapies. The main objective of this review is to discuss the various natural compounds, so far identified and their employed mechanisms in hindering the genes responsible for QS leading to bacterial pathogenesis.