A comprehensive guide on screening and selection of a suitable AMP against biofilm-forming bacteria.

Lately, antimicrobial resistance (AMR) is increasing at an exponential rate making it important to search alternatives to antibiotics in order to combat multi-drug resistant (MDR) bacterial infections. Out of the several antibacterial and antibiofilm strategies being tested, antimicrobial peptides (AMPs) have shown to give better hopes in terms of a long-lasting solution to the problem. To select a desired AMP, it is important to make right use of available tools and databases that aid in identification, classification, and analysis of the physiochemical properties of AMPs. To identify the targets of these AMPs, it becomes crucial to understand their mode-of-action. AMPs can also be used in combination with other antibacterial and antibiofilm agents so as to achieve enhanced efficacy against bacteria and their biofilms. Due to concerns regarding toxicity, stability, and bioavailability, strategizing drug formulation at an early-stage becomes crucial. Although there are few concerns regarding development of bacterial resistance to AMPs, the evolution of resistance to AMPs occurs extremely slowly. This comprehensive review gives a deep insight into the selection of the right AMP, deciding the right target and combination strategy along with the type of formulation needed, and the possible resistance that bacteria can develop to these AMPs.

Combination therapy of biogenic C-dots and lysozyme for enhanced antibacterial and antibiofilm activity.

Nearly 80% of human chronic infections are caused due to bacterial biofilm formation. The increased resistance against the conventional antimicrobial agents makes it difficult to treat the biofilm-related infections. The antibiotics resistance developed by planktonic cells has also become a major threat for human. Therefore, we have attempted here to develop an effective alternative strategy to overcome the issues of antibiotics resistance of bacteria. Upon synthesis, biogenic C-dots were combined with lysozymes which were further encapsulated into chitosan nanocarrier to form C-dots carrier (CDC). The as-synthesized C-dots were found irregular shaped and the average size of C-dots and CDC were 8 ± 2 nm and 450 ± 50 nm, respectively. To ensure secure and targeted delivery of C-dots and lysozyme we have employed chitosan, a biodegradable and natural biopolymer, as a delivery system. The study of time-dependent bacterial growth and flow cytometry analysis demonstrated that CDC can exhibit a synergistic bactericidal activity against the antibiotics resistant recombinant E. coli cells. Further, we have shown that the CDC could be a potent agent for both prevention of biofilm formation and eradication of preformed biofilm. In addition, we have observed that our drug delivery system is hemocompatible in nature making it suitable for in vivo applications. Therefore, we believe that the combination therapy of C-dots and lysozyme may be used as an excellent antibacterial and antibiofilm strategy.

Outbreak of COVID-19: A Detailed Overview and Its Consequences.

INTRODUCTION: After the outbreak from Wuhan City of China, COVID-19, caused by SARS-CoV-2, has become a pandemic worldwide in a very short span of time. The high transmission rate and pathogenicity of this virus have made COVID-19 a major public health concern globally. Basically, the emergence of SARS-CoV-2 is the third introduction of a highly infectious human epidemic coronavirus in the twenty-first century. Various research groups have claimed bats to be the natural host of SARS-CoV-2. However, the intermediate host and mode of transmission from bat to humans are not revealed yet. The COVID-19 cost hundreds and thousands of lives and millions are facing the consequences. The objective of this chapter was to analyze the outbreak of COVID-19 and problems faced globally. METHODS: All published relevant literature from scientific sources and reputed news channels are considered to write the current review. RESULTS: Generally, elder persons and more particularly people with underlying medical conditions are found to be highly vulnerable to severe infection and prone to fatal outcomes. Unfortunately, there is no specific treatment with clinically approved drugs or vaccines to treat this disease. Several research groups have been investigating the efficacies of several antiviral and repurposed drugs. Currently, most of the SARS-COV-2 vaccines are at the preclinical or clinical stage of development. The latest research progress on the epidemiology, clinical characteristics, pathogenesis, diagnosis, and current status of therapeutic intervention indicates that still a specific drug or vaccine needs to come up for the effective treatment of the pandemic COVID-19. It is observed that various aspects of social life, economic status, and healthcare systems are majorly affected by this pandemic. CONCLUSION: It is concluded that the outbreak of COVID-19 has severely affected each and every field, such as social, scientific, industrial, transport, and medical sectors. Irrespective of tremendous efforts globally, few vaccines are now available for the prevention of the disease. Specific drug is not available publicly for the treatment of COVID-19. Prevention of air pollution that can aggravate COVID-19 has been suggested. Therefore, as of now, social distancing and sanitization practices are the only options available for the prevention of the disease for many.

Recent development of autonomously driven micro/nanobots for efficient treatment of polluted water.

Autonomously propelled micro/nanobots are one of the most advanced and integrated structures which have been fascinated researchers owing to its exceptional property that enables them to be carried out user-defined tasks more precisely even on an atomic scale. The unique architecture and engineering aspects of these manmade tiny devices make them viable options for widespread biomedical applications. Moreover, recent development in this line of interest demonstrated that micro/nanobots would be very promising for the water treatment as these can efficiently absorb or degrade the toxic chemicals from the polluted water based on their tunable surface chemistry. These auto propelled micro/nanobots catalytically degrade toxic pollutants into non-hazardous compounds more rapidly and effectively. Thus, for the last few decades, nanobots mediated water treatment gaining huge popularity due to its ease of operation and scope of guided motion that could be monitored by various external fields and stimuli. Also, these are economical, energy-saving, and suitable for large scale water treatment, particularly required for industrial effluents. However, the efficacy of these bots hugely relies on its design, characteristic of materials, properties of the medium, types of fuel, and surface functional groups. Minute variation for one of these things may lead to a change in its performance and hinders its dynamics of propulsion. It is deemed that nanobots might be a smart choice for using these as the new generation devices for treating industrial effluents before discharging it in the water bodies, which is a major concern for human health and the environment.

Autonomous magnetic microbots for environmental remediation developed by organic waste derived carbon dots.

Biodegradable precursors for micro/nanobots development are key requirements for several sustainable applications. In this regard, we propose an innovative solution for water purification at minimum cost and efforts where organic waste is used for the treatment of organic pollutants. Herein, catalytic magnetic microbots were developed by functionalizing iron oxide nanoparticles with carbon dots (C-Dots), which were synthesized by using household waste such as potato peels as precursors. The speed of these autonomously propelling bots indeed is found very promising for large distance swimming even in viscous medium by using hydrogen peroxide as fuel. These microbots catalytically propel and degrade toxic polar as well as sparingly water-soluble industrial dyes without any external agitation. The degradation of dyes was confirmed by mass-spectra analysis. Furthermore, these microbots can efficiently degrade a mixture of dyes and reused without compromising its performance significantly. Additionally, rate constant (K) and activation energy (Ea) were also determined to establish the catalytic nature of the bots. The present microbots acted as nanozyme owing to its synergistic catalytic activity of Fe3O4 and C-Dots for degradation of mixture of toxic dyes, essential for large scale water treatment.

Role of surface charge in enhancing antibacterial activity of fluorescent carbon dots.

Herein, different surface charged carbon dots (Cdots) were synthesized by using diethylene glycol as a carbon source with various amine containing surface passivating agents. The synthesis method is very simple and fast microwave oven-based, that results in almost similar sized positive, negative and uncharged fluorescent Cdots which has been confirmed by zeta potential analysis in our case. The formation of Cdots was confirmed by characterization using fluorescence spectroscopy, transmission electron microscopy, XRD, FT-IR, and XPS spectroscopy. To find out relative bactericidal activity of these Cdots, green fluorescence protein expressing recombinant E. coli bacteria were taken as a model system. Time-dependent bacterial growth and FACS study demonstrated that both uncharged Cdots and positively charged Cdots were showing better bactericidal activity as compared to negative charged Cdots. The Cdots caused elevation of reactive oxygen species level, which is possibly leading to bacterial cell death.

Synthesis and applications of biogenic nanomaterials in drinking and wastewater treatment.

The continuous increase in water pollution by various organic & inorganic contaminants has become a major issue of concern worldwide. Furthermore, the anthropogenic activities for the manufacturing of various products have boosted this problem manifold. To overcome this serious issue, nanotechnology has initiated to explore various proficient strategies to treat waste water in a more precise and accurate way with the support of various nanomaterials. In recent times, nanosized materials have proved their applicability to provide clean and affordable water treatment technologies. The exclusive features such as high surface area and mechanical properties, greater chemical reactivity, lower cost and energy, efficient regeneration for reuse allow the nanomaterials perfect for water remediation. But the conventional routes of synthesis of nanomaterials encompass the involvement of hazardous and volatile chemicals; therefore the use of nanomaterials further creates the secondary pollution. This issue has intrigued the scientists to develop biogenic pathways and procedures which are environmentally safer and inexpensive. It has led to the new trends that involve developing bio-inspired nano-scale adsorbents and catalysts for the removal and degradation of a wide range of water pollutants. Carbohydrates, proteins, polymers, flavonoids, alkaloids and several antioxidants obtained from plants, bacteria, fungi, and algae have proven their effectiveness as capping and stabilizing agents during manufacture of nanomaterials. Application of biogenic nanomaterials for waste water treatment is relatively newer but rapidly escalating area of research. In the present review, promises and challenges for the synthesis of various biogenic nanomaterials and their potential applications in waste water treatment and/or water purification have been discussed.

Developing anti-microbial peptide database version 1 to provide comprehensive and exhaustive resource of manually curated AMPs.

Anti-Microbial Peptide Database version 1 (AMPDB v1) is a meticulously curated resource that aims to address the limitations of existing databases in the field of antimicrobial research. We have utilized the latest technology and put our best efforts into adding all relevant tools to cater to the needs of our users. AMPDB v1 is a derived database, built upon information gathered from the available resources and boasts a significant size of 59,122 entries which are classified into 88 classes. All the information in this resource was curated manually. Sequence alignment and protein feature calculation tools were integrated into the database in the form of web applications, to make them easy to use, quick, and responsive in real-time. We have included multiple types of browsing and searching options to enhance the user experience, from simple text search to a completely customizable advanced search page with intuitive options that let the user combine multiple options together to make a powerful search query. The database is accessible by a web browser at https://bblserver.org.in/ampdb/ .

Docking and molecular dynamics simulation for therapeutic repurposing in small cell lung cancer (SCLC) patients infected with COVID-19.

Cancer care has become a challenge with the current COVID-19 pandemic scenario. Specially, cancers like small cell lung cancers (SCLC) are difficult to treat even in the normal situation due to their rapid growth and early metastasis. For such patients, treatment can't be compromised and care must be taken to ensure their minimum exposure to the ongoing spread of COVID-19 infection. For this reason, in-house treatments are being suggested for these patients. Another issue is that symptoms of SCLC match well with that of COVID-19 infection. Hence, the detection of COVID-19 may also get delayed leading to unnecessary complications. Thus, we have tried to investigate if the therapeutics that is currently used in lung cancer treatment can also act against SARS-CoV-2. If it is so, the same treatment protocols can be continued even if the SCLC patient had contracted COVID-19 without compromising the cancer care. For this, RNA dependent RNA polymerase (RdRP) from SARS-CoV-2 has been selected as drug target. Both docking and molecular dynamicssimulation analysis have indicated that Paclitaxel and Dacomitinib may be explored as multi-target drugs for both SCLC and COVID-19.Communicated by Ramaswamy H. Sarma.

Identification of candidate target genes of oral squamous cell carcinoma using high-throughput RNA-Seq data and in silico studies of their interaction with naturally occurring bioactive compounds.

Oral Squamous Cell Carcinoma (OSCC) accounts for more than 90% of all kinds of oral neoplasms that develop in the oral cavity. It is a type of malignancy that shows high morbidity and recurrence rate, but data on the disease's target genes and biomarkers is still insufficient. In this study, in silico studies have been performed to find out the novel target genes and their potential therapeutic inhibitors for the effective and efficient treatment of OSCC. The DESeq2 package of RStudio was used in the current investigation to screen and identify differentially expressed genes for OSCC. As a result of gene expression analysis, the top 10 novel genes were identified using the Cytohubba plugin of Cytoscape, and among them, the ubiquitin-conjugating enzyme (UBE2D1) was found to be upregulated and playing a significant role in the progression of human oral cancers. Following this, naturally occurring compounds were virtually evaluated and simulated against the discovered novel target as prospective drugs utilizing the Maestro, Schrodinger, and Gromacs software. In a simulated screening of naturally occurring potential inhibitors against the novel target UBE2D1, Epigallocatechin 3-gallate, Quercetin, Luteoline, Curcumin, and Baicalein were identified as potent inhibitors. Novel identified gene UBE2D1 has a significant role in the proliferation of human cancers through suppression of 'guardian of genome' p53 via ubiquitination dependent pathway. Therefore, the treatment of OSCC may benefit significantly from targeting this gene and its discovered naturally occurring inhibitors.Communicated by Ramaswamy H. Sarma.

Finding Novel AMPs Secreted from the Human Microbiome as Potent Antibacterial and Antibiofilm Agents and Studying Their Synergistic Activity with Ag NCs.

Due to the enhanced resistance of bacteria to antibiotics, researchers always try to find effective alternatives to treat drug-resistant bacterial infections. In this context, we have explored antimicrobial peptides (AMPs), which are a broad class of small peptide molecules, and investigated their efficacy as potent antibacterial and antibiofilm agents. AMPs can cause cell death either through disruption of the cell membrane or by inhibiting vital intracellular functions, by binding to RNA, DNA, or intracellular components upon transversion through the cell membrane. We attempted to find potent intracellular cationic AMPs that can demonstrate antibacterial activity through interaction with DNA. As a source of AMPs, we have utilized those that are secreted from the human microbiome with the anticipation that these will be non-toxic in nature. Out of the total 1087 AMPs, 27 were screened on the basis of amino acid length and efficacy to cross the cell membrane barrier. From the list of 27 peptides, 4 candidates were selected through the docking score of these peptides with the DNA binding domain of H2A proteins. Further, the molecular dynamics simulation analysis demonstrated that 2 AMPs, i.e., peptides 7 and 25, are having considerable membrane permeation and DNA binding ability. Further, the in vitro analysis indicated that both peptides 7 and 25 could exhibit potent antibacterial and antibiofilm activities. In order to further enhance the antibiofilm potency, the above AMPs were used as supplements to silver nanoclusters (Ag NCs) to get synergistic activity. The synergistic activity of Ag NCs was found to be significantly increased with both the above AMPs.

Nanoengineering of biohybrid micro/nanobots for programmed biomedical applications.

Biohybrid micro/nanobots have emerged as an innovative resource to be employed in the biomedical field due to their biocompatible and biodegradable properties. These are tiny nanomaterial-based integrated structures engineered in a way that they can move autonomously and perform the programmed tasks efficiently even at hard-to-reach organ/tissues/cellular sites. The biohybrid micro/nanobots can either be cell/bacterial/enzyme-based or may mimic the properties of an active molecule. It holds the potential to change the landscape in various areas of biomedical including early diagnosis of disease, therapeutics, imaging, or precision surgery. The propulsion mechanism of the biohybrid micro/nanobots can be both fuel-based and fuel-free, but the most effective and easiest way to propel these micro/nanobots is via enzymes. Micro/nanobots possess the feature to adsorb/functionalize chemicals or drugs at their surfaces thus offering the scope of delivering drugs at the targeted locations. They also have shown immense potential in intracellular sensing of biomolecules and molecular events. Moreover, with recent progress in the material development and processing is required for enhanced activity and robustness the fabrication is done via various advanced techniques to avoid self-degradation and cause cellular toxicity during autonomous movement in biological medium. In this review, various approaches of design, architecture, and performance of such micro/nanobots have been illustrated along with their potential applications in controlled cargo release, therapeutics, intracellular sensing, and bioimaging. Furthermore, it is also foregrounding their advancement offering an insight into their future scopes, opportunities, and challenges involved in advanced biomedical applications.

In Silico Study of a Small Bioactive Molecule Targeting Topoisomerase II and P53-MDM2 Complex in Triple-Negative Breast Cancer.

Treatment of triple-negative breast cancer (TNBC) is very challenging as only few therapeutic options are available, including chemotherapy. Thus, a constant search for new and effective approaches of therapy that could potentially fight against TNBC and mitigate side effects is "turn-on". Recently, multitarget therapy has come up with huge possibilities, and it may possibly be useful to overcome several concurrent challenges in cancer therapy. Herein, we proposed the inhibition of both Topoisomerase II enzyme and p53-MDM2 (p53 cavity in MDM2) protein complex by the same bioactive molecules for multitarget therapy. RNA-seq analysis was performed to get a network of essential proteins involved in the apoptosis pathway by considering the triple-negative breast cancer cell line (MDA-MB-231). All of the untreated duplicate sample data were retrieved from NCBI (GSC149768). Further, via in silico screening, potent bioactive molecules were screened out to target both Topo II and the p53-MDM2 complex. The results of ligand-based screening involving docking, MMGBSA, ADME/T, MD simulation, and PCA suggested that resveratrol, a plant bioactive molecule, showed more potential binding in the same cavity of target proteins compared with doxorubicin for Topo IIα (5GWK) and etoposide for the second protein target (p53-MDM2 complex; 4OQ3) as the control drug. This is also evident from the in vitro validation in case of triple-negative breast cancer cell lines (MDA-MB-231) and Western blotting analysis. Thus, it paves the scope of multitargeting against triple-negative breast cancer.

Strategies in design of self-propelling hybrid micro/nanobots for bioengineering applications.

Micro/nanobots are integrated devices developed from engineered nanomaterials that have evolved significantly over the past decades. They can potentially be pre-programmed to operate robustly at numerous hard-to-reach organ/tissues/cellular sites for multiple bioengineering applications such as early disease diagnosis, precision surgeries, targeted drug delivery, cancer therapeutics, bio-imaging, biomolecules isolation, detoxification, bio-sensing, and clearing up clogged arteries with high soaring effectiveness and minimal exhaustion of power. Several techniques have been introduced in recent years to develop programmable, biocompatible, and energy-efficient micro/nanobots. Therefore, the primary focus of most of these techniques is to develop hybrid micro/nanobots that are an optimized combination of purely synthetic or biodegradable bots suitable for the execution of user-defined tasks more precisely and efficiently. Recent progress has been illustrated here as an overview of a few of the achievable construction principles to be used to make biomedical micro/nanobots and explores the pivotal ventures of nanotechnology-moderated development of catalytic autonomous bots. Furthermore, it is also foregrounding their advancement offering an insight into the recent trends and subsequent prospects, opportunities, and challenges involved in the accomplishments of the effective multifarious bioengineering applications.

Neolamarckia cadamba (Roxb.) Bosser (Rubiaceae) extracts: promising prospects for anticancer and antibacterial potential through in vitro and in silico studies.

Neolamarckia cadamba is an Indian traditional medicinal plant having various therapeutic potentials. In the present study, we did solvent-based extraction of Neolamarckia cadamba leaves. The extracted samples were screened against liver cancer cell line (HepG2) and bacteria (Escherichia coli). MTT cytotoxic assay was performed for in vitro analysis of extracted samples against the HepG2 cell lines and the normal human prostate PNT2 cell line. Chloroform extract of Neolamarckia cadamba leaves showed better activity with IC50 value 69 µg/ml. DH5α strain of Escherichia coli (E. coli) was cultured in Luria Bertani (LB) broth media and minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were calculated. Solvent extract chloroform showed better activity in MTT analysis and antibacterial screening and it was taken for characterization of phytocomposition by Fourier transform infrared (FTIR) and gas chromatography mass spectrometry (GC-MS). The identified phytoconstituents were docked with potential targets of liver cancer and E. coli. The phytochemical 1-(5-Hydroxy-6-hydroxymethyl-tetrahydropyran-2-yl)-5-methyl-1H-pyrimidine-2,4-dione shows highest docking score against the targets PDGFRA (PDB ID: 6JOL) and Beta-ketoacyl synthase 1(PDB ID: 1FJ4) and their stability was further confirmed by molecular dynamics simulation studies.

Identification of naturally occurring compounds as alternatives to radiation therapy for treatment of small cell lung cancer.

Radiation resistance is one of the major problems in the treatment of small cell lung cancer (SCLC). Most of these patients are given radiation as first-line treatment and it was observed that the initial response in these patients is very good. However, they show relapse in a few months which is also associated with resistance to treatment. Thus, targeting the mechanism by which these cells develop resistance could be an important strategy to improve the survival chances of these patients. From the RNA-Seq data analysis, it was identified that CHEK1 gene was overexpressed. Chk1 protein which is encoded by the CHEK1 gene is an important protein that is involved in radiation resistance in SCLC. It is known to favour the cells to deal with replicative stress. CHEK1 is the major cause for developing radiation resistance in SCLC. Thus, natural compounds that could also serve as potential inhibitors for Chk1 were explored. Accordingly; the compounds were screened based on ADME, docking and MM-GBSA scores. MD simulations were performed for the selected protein-ligand complexes and the results were compared to the co-crystallised ligand, 3-(indol-2-yl)indazole. The results showed that compound INC000033832986 could be a natural alternative to the commercial ligand for the prevention of SCLC.Communicated by Ramaswamy H. Sarma.

Stress-responsive AMP Kinase like protein regulates encystation of Entamoeba invadens.

Starvation is always accompanied by an increase in the ratio of AMP/ATP followed by activation of AMPK. It is one of the sensors for cellular energy status and is highly conserved across various species. Its role in the stage differentiation process of protozoan species like Giardia, Plasmodium, Trypanosome, and Toxoplasma has been reported. Since Entamoeba undergoes encystation in glucose-starved conditions; it intrigued us to investigate the existence and role of AMPK during the differentiation of trophozoites to the cyst. By employing in silico approaches, we have identified an AMPK homologue which is denominated here as EiAMPK (AMPK-like protein in Entamoeba invadens). Sequence and structural analysis indicate that EiAMPK is sequentially and structurally similar to the AMPK alpha subunit of other organisms. The recombinant form of EiAMPK was functionally active and in accordance, its activity was inhibited by an AMPK-specific inhibitor (eg. Compound C). The increased expression of EiAMPK during different stresses indicated that EiAMPK is a stress-responsive gene. To further investigate, whether EiAMPK has any role in encystation, we employed RNAi-mediated gene silencing that demonstrated its active involvement in encystation. It is known that Entamoeba maintains a flow of glucose from the glycolytic pathway to chitin synthesis for cyst wall formation during encystation. It is conceivable that EiAMPK might have a command over such glucose metabolism. As anticipated, the chitin synthesis was found greatly inhibited in both EiAMPK knockdown and Compound C treated cells, indicating that EiAMPK regulates the cyst wall chitin synthesis.

Naturally occurring anthraquinones as potential inhibitors of SARS-CoV-2 main protease: an integrated computational study.

The novel coronavirus disease (COVID-19) has spread throughout the globe, affecting millions of people. The World Health Organization (WHO) has declared this infectious disease a pandemic. At present, several clinical trials are going on to identify possible drugs for treating this infection. SARS-CoV-2 Mpro is one of the most critical drug targets for the blockage of viral replication. The aim of this study was to identify potential natural anthraquinones that could bind to the active site of SARS-CoV-2 main protease and stop the viral replication. Blind molecular docking studies of 13 anthraquinones and one control drug (Boceprevir) with SARS-CoV-2 Mpro were carried out using the SwissDOCK server, and alterporriol-Q that showed the highest binding affinity towards Mpro were subjected to molecular dynamics simulation studies. This study indicated that several antiviral anthraquinones could prove to be effective inhibitors for SARS-CoV-2 Mpro of COVID-19 as they bind near the active site having the catalytic dyad, HIS41 and CYS145 through non-covalent forces. The anthraquinones showed less inhibitory potential as compared to the FDA-approved drug, boceprevir. Among the anthraquinones studied, alterporriol-Q was found to be the most potent inhibitor of SARS-CoV-2 Mpro. Further, MD simulation studies for Mpro- alterporriol-Q system suggested that alterporriol-Q does not alter the structure of Mpro to a significant extent. Considering the impact of COVID-19, identification of alternate compounds like alterporriol-Q that could inhibit the viral infection will help in accelerating the process of drug discovery. Supplementary Information: The online version contains supplementary material available at 10.1007/s11756-021-01004-4.

Ag NCs as a potent antibiofilm agent against pathogenic Pseudomonas aeruginosa and Acinetobacter baumannii and drug-resistant Bacillus subtilis by affecting chemotaxis and flagellar assembly pathway genes.

Biofilm infections are highly resistant to commercial antibiotics. Therefore, developing a potent agent against such drug-resistant bacterial infections is highly desirable. Here, we synthesized positively charged silver nanoclusters (Ag NCs) with a diameter of <2 nm, which were found to be very effective antibacterial and antibiofilm agents against tetracycline-resistant Bacillus subtilis and most importantly multidrug-resistant pathogenic strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Ag NCs were able to both prevent and eradicate the biofilm formation very effectively. The antibiofilm activity can be significantly increased with α-amylase and/or DNase which degrade the structural components of biofilms. The antibiofilm activity of antibiotics gets considerably lowered due to poor penetration and the acidic microenvironment of biofilms. However, the potency of antibiotics gets significantly increased when applied with Ag NCs. Finally, RNA seq-based analysis has demonstrated that the biofilm degradation was likely due to the regulation of bacterial chemotaxis and flagellar assembly pathway genes by Ag NCs.

Bacterial biofilm infections, their resistance to antibiotics therapy and current treatment strategies.

Nearly 80% of human chronic infections are caused due to bacterial biofilm formation. This is the most leading cause for failure of medical implants resulting in high morbidity and mortality. In addition, biofilms are also known to cause serious problems in food industry. Biofilm impart enhanced antibiotic resistance and become recalcitrant to host immune responses leading to persistent and recurrent infections. It makes the clinical treatment for biofilm infections very difficult. Reduced penetration of antibiotic molecules through EPS, mutation of the target site, accumulation of antibiotic degrading enzymes, enhanced expression of efflux pump genes are the probable causes for antibiotics resistance. Accordingly, strategies like administration of topical antibiotics and combined therapy of antibiotics with antimicrobial peptides are considered for alternate options to overcome the antibiotics resistance. A number of other remediation strategies for both biofilm inhibition and dispersion of established biofilm have been developed. The metallic nanoparticles (NPs) and their oxides have recently gained a tremendous thrust as antibiofilm therapy for their unique features. This present comprehensive review gives the understanding of antibiotic resistance mechanisms of biofilm and provides an overview of various currently available biofilm remediation strategies, focusing primarily on the applications of metallic NPs and their oxides.