RESUMO
In the last few years, there has been a necessary demand in the pharmaceutical industries for finding a treatment against biofilms formed by different bacterial species. We are aware of the fact that classical processes, which are already there for the removal of bacterial biofilms gives a very low efficiency and consequently antimicrobial resistance makes it even worse. To cope up with the cited problems, scientists from the past few years are inclining toward various types of nanoparticle based treatment procedures as a pharmaceutical agent against bacterial biofilms. Nanoparticles are known for their extremely efficient antimicrobial properties. The current review gives a description of different types of metal oxide nanoparticles and their antibiofilm properties. It also shows a comparative analysis of the nanoparticles and depicts the efficiency rates of biofilm degradation in each of them. It explains the mechanism of the nanoparticles through which the disintegration of bacterial biofilm is carried out. Lastly, the review throws light upon the limitations of different nanoparticles, their safety issues, the mutagenicity, genotoxicity concerns, and toxicity hazards caused by them.
Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Nanopartículas , Óxidos/farmacologia , Antibacterianos/farmacologia , Bactérias , Biofilmes , Metais/farmacologiaRESUMO
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.
Assuntos
Arabidopsis/enzimologia , Bacillus cereus/enzimologia , Proteínas de Bactérias/biossíntese , Clostridium/enzimologia , Proteínas de Plantas/biossíntese , beta-Amilase/biossíntese , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Domínio Catalítico , Regulação Bacteriana da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Maltose/metabolismo , Engenharia Metabólica/métodos , Proteínas de Plantas/química , Proteínas de Plantas/genética , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Amido/metabolismo , Estresse Fisiológico/genética , beta-Amilase/química , beta-Amilase/genéticaRESUMO
Bioengineered composite hydrogel platforms made of a supramolecular coassembly have recently garnered significant attention as promising biomaterial-based healthcare therapeutics. The mechanical durability of amyloids, in conjunction with the structured charged framework rendered by biologically abundant key ECM component glycosaminoglycan, enables us to design minimalistic customized biomaterial suited for stimuli responsive therapy. In this study, by harnessing the heparin sulfate-binding aptitude of amyloid fibrils, we have constructed a pH-responsive extracellular matrix (ECM) mimicking hydrogel matrix. This effective biocompatible platform comprising heparin sulfate-amyloid coassembled hydrogel embedded with polyphenol functionalized silver nanoparticles not only provide a native skin ECM-like conductive environment but also provide wound-microenvironment responsive on-demand superior antibacterial efficacy for effective diabetic wound healing. Interestingly, both the cytocompatibility and antibacterial properties of this bioinspired matrix can be fine-tuned by controlling the mutual ratio of heparin sulfate-amyloid and incubated silver nanoparticle components, respectively. The designed biomaterial platform exhibits notable effectiveness in the treatment of chronic hyperglycemic wounds infected with multidrug-resistant bacteria, because of the integration of pH-responsive release characteristics of the incubated functionalized AgNP and the antibacterial amyloid fibrils. In addition to this, the aforementioned assemblage shows exceptional hemocompatibility with significant antibiofilm and antioxidant characteristics. Histological evidence of the incised skin tissue sections indicates that the fabricated composite hydrogel is also effective in controlling pro-inflammatory cytokines such as IL6 and TNFα expressions at the wound vicinity with significant upregulation of angiogenesis markers like CD31 and α-SMA.
Assuntos
Amiloide , Antibacterianos , Matriz Extracelular , Heparina , Hidrogéis , Nanopartículas Metálicas , Prata , Cicatrização , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Heparina/química , Heparina/farmacologia , Prata/química , Prata/farmacologia , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Nanopartículas Metálicas/química , Amiloide/química , Amiloide/metabolismo , Animais , Humanos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
The emergence of antimicrobial resistance, exemplified by methicillin-resistant Staphylococcus aureus (MRSA), poses a grave threat to public health globally. Over time, MRSA has evolved resistance to multiple antibiotics, challenging conventional treatment strategies. The relentless adaptability of MRSA underscores the urgent need for innovative and targeted antimicrobial approaches to combat this resilient pathogen. Ancient knowledge and practices, along with scientific evidence, have established that metallic copper, and its organic coordination complexes can act as potential antibacterial substances. In search of a smart and effective antimicrobial against MRSA, we designed, synthesized, and characterized a bidentate copper(II) ligand complex (SG-Cu) utilizing a comprehensive array of analytical techniques, including ESI-MS, elemental analysis, X-ray photoelectron spectroscopy, electron paramagnetic resonance spectroscopy, and others. Antibacterial efficacy and mechanism of action of the complex were assessed through bacterial growth analyses, bacterial membrane perturbation assays, ROS elicitation assays, and field emission scanning electron microscopy. SG-Cu was found to maintain robust biocompatibility against the mammalian cell lines HEK-293, WI-38, and NIH/3T3. Remarkably, SG-Cu demonstrated significant biofilm disruptive tendency evidenced by the retardation of sliding motility, reduction in slime production, reduction in biofilm viability, and enhanced biofilm eradication, both in vitro and in urinary catheters. In vivo studies on murine excisional wounds, with SG-Cu impregnated in a palmitic acid conjugated NAVSIQ hexapeptide (PA-NV) hydrogel, revealed the sustained release of SG-Cu from the gel matrix, facilitating accelerated wound healing and effective wound disinfection. This multifaceted investigation highlights the potential of SG-Cu as a versatile option for combating MRSA infections and promoting wound healing, solidifying its claim to be developed into a viable therapeutic.
Assuntos
Antibacterianos , Cobre , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Quinolinas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Animais , Quinolinas/química , Quinolinas/farmacologia , Ligantes , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Biofilmes/efeitos dos fármacos , Tamanho da Partícula , Cicatrização/efeitos dos fármacos , Teste de Materiais , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Estrutura MolecularRESUMO
The escalation of bacterial resistance against existing therapeutic antimicrobials has reached a critical peak, leading to the rapid emergence of multidrug-resistant strains. Stringent pathways in novel drug discovery hinder our progress in this survival race. A promising approach to combat emerging antibiotic resistance involves enhancing conventional ineffective antimicrobials using low-toxicity small molecule adjuvants. Recent research interest lies in weak membrane-perturbing agents with unique cyclic hydrophobic components, addressing a significant gap in antimicrobial drug exploration. Our study demonstrates that quinoline-based amphipathic small molecules, SG-B-52 and SG-B-22, significantly reduce MICs of selected beta-lactam antibiotics (ampicillin and amoxicillin) against lethal methicillin-resistant Staphylococcus aureus (MRSA). Mechanistically, membrane perturbation, depolarization, and ROS generation drive cellular lysis and death. These molecules display minimal in vitro and in vivo toxicity, showcased through hemolysis assays, cell cytotoxicity analysis, and studies on albino Wistar rats. SG-B-52 exhibits impressive biofilm-clearing abilities against MRSA biofilms, proposing a strategy to enhance beta-lactam antibiosis and encouraging the development of potent antimicrobial potentiators.
Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Quinolinas , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico , Sinergismo Farmacológico , Anti-Infecciosos/farmacologia , Quinolinas/farmacologiaRESUMO
In pharmaceutical industries, various chemical carriers are present which are used for drug delivery to the correct target sites. The most popular and upcoming drug delivery carriers are mesoporous silica nanoparticles (MSN). The main reason for its popularity is its ability to be specific and optimize the drug delivery process in a controlled manner. Nowadays, MSNs are widely used to eradicate various microbial infections, especially the ones related to biofilms. Biofilms are sessile groups of cells that live by forming a consortium and exhibit antibacterial resistance (AMR). They exhibit AMR by extracellular polymeric substances (EPS) and various quorum sensing (QS) signaling molecules. Usually, bacterial and fungal cells are capable of forming biofilms. These biofilms are pathogenic. In the majority of the cases, biofilms cause nosocomial diseases. This review will focus on the antibiofilm activities of MSN, its mechanism of target-specific drug delivery, and its ability to disrupt the bacterial biofilms inhibiting the infection. The review will also discuss various mechanisms for the delivery of pharmaceutical molecules by the MSNs to inhibit the bacterial biofilms, and lastly, we will talk about the different types of MSNs and their antibiofilm activities.
RESUMO
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.
Assuntos
Leonurus , Pseudomonas aeruginosa , Pseudomonas aeruginosa/metabolismo , Leonurus/metabolismo , Simulação de Acoplamento Molecular , Quercetina , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes , Fatores de Virulência/metabolismoRESUMO
Biofilm is a syntrophic association of sessile groups of microbial cells that adhere to biotic and abiotic surfaces with the help of pili and extracellular polymeric substances (EPS). EPSs also prevent penetration of antimicrobials/antibiotics into the sessile groups of cells. Hence, methods and agents to avoid or remove biofilms are urgently needed. Enzymes play important roles in the removal of biofilm in natural environments and may be promising agents for this purpose. As the major component of the EPS is polysaccharide, amylase has inhibited EPS by preventing the adherence of the microbial cells, thus making amylase a suitable antimicrobial agent. On the other hand, salivary amylase binds to amylase-binding protein of plaque-forming Streptococci and initiates the formation of biofilm. This review investigates the contradictory actions and microbe-associated genes of amylases, with emphasis on their structural and functional characteristics.
Assuntos
Amilases , Biofilmes , Antibacterianos , Fímbrias Bacterianas , StreptococcusRESUMO
The biggest challenge in the present-day healthcare scenario is the rapid emergence and spread of antimicrobial resistance due to the rampant use of antibiotics in daily therapeutics. Such drug resistance is associated with the enhancement of microbial virulence and the acquisition of the ability to evade the host's immune response under the shelter of a biofilm. Quorum sensing (QS) is the mechanism by which the microbial colonies in a biofilm modulate and intercept communication without direct interaction. Hence, the eradication of biofilms through hindering this communication will lead to the successful management of drug resistance and may be a novel target for antimicrobial chemotherapy. Chitosan shows microbicidal activities by acting electrostatically with its positively charged amino groups, which interact with anionic moieties on microbial species, causing enhanced membrane permeability and eventual cell death. Therefore, nanoparticles (NPs) prepared with chitosan possess a positive surface charge and mucoadhesive properties that can adhere to microbial mucus membranes and release their drug load in a constant release manner. As the success in therapeutics depends on the targeted delivery of drugs, chitosan nanomaterial, which displays low toxicity, can be safely used for eradicating a biofilm through attenuating the quorum sensing (QS). Since the anti-biofilm potential of chitosan and its nano-derivatives are reported for various microorganisms, these can be used as attractive tools for combating chronic infections and for the preparation of functionalized nanomaterials for different medical devices, such as orthodontic appliances. This mini-review focuses on the mechanism of the downregulation of quorum sensing using functionalized chitosan nanomaterials and the future prospects of its applications.