Broad-spectrum Antibacterial Activity Research Articles

The Ocular Chloramphenicol Story

Chloramphenicol eye drops and ointment are the most used ocular antibiotic worldwide. Chloramphenicol was discovered in 1947 and was only the third antibiotic to successfully be produced and only the first antibiotic suitable for large-scale commercial production. By the 1950s, the drug had been developed into drop and ointment forms. The broad spectrum of anti-bacterial activity of Chloramphenicol led to widespread use. Ocular Chloramphenicol remains an important weapon in the ophthalmic armamentarium despite emergence of evidence of possible side effects in the 1970s. This is a short review of the remarkable story of the discovery, development and tribulations of ocular Chloramphenicol. Keywords: History; Chloramphenicol Abbreviations: FDA: Food and Drug Administration

Characterization of antibiofilm compound from marine sponge Stylissa carteri.

The fouling phenomenon grabbed global attention and caused huge economic losses specifically in marine-related industries. Sessile behavior exposed the sponge to the risk of fouling. However, their bodies remained free from foulers, which were attributed to the chemical defense system. The objectives of this study were to determine the antibiofilm activity of the marine sponge, Stylissa carteri, and to characterize the isolated compound involved. The antibiofilm activity of S. carteri methanolic crude extract (MCE) and fractions was tested against biofilm-producing bacteria, Pseudomonas aeruginosa, using two different modes of crystal violet biofilm assays: preventive and detachment. Besides that, the disc-diffusion test was conducted to screen the antibacterial activity against gram-positive and gram-negative bacteria while a cytotoxicity assay was conducted on the HepG2 cell line. Bioassay-guided fractionation was carried out using vacuum liquid chromatography (VLC) and solid phase extraction using a C18 Sep-Pak Cartridge. The crystal compound was isolated and characterized through thin-layer chromatography (TLC), Fourier transform infrared (FTIR) spectroscopy, liquid chromatography-mass spectrometry (LCMS), and nuclear magnetic resonance (NMR) spectroscopy. The S. carteri MCE showed a promising result with a half-maximal inhibitory concentration (IC50) of 20.22μg/mL in the preventive assay, while no IC50 was determined in the detachment assay since all inhibitions < 50%. The S. carteri MCE exhibited broad-spectrum antibacterial activity and displayed a non-cytotoxic effect. Fraction 4 from MCE of S. carteri (IC50 = 2.40μg/mL) reduced the biofilm in the preventive assay at all concentrations and exhibited no antibacterial activity indicating the independence of antibiofilm from antibacterial properties. Based on the data obtained, an alkaloid named debromohymenialdisine (DBH) was identified from Fraction 4 of S. carteri MCE. In conclusion, S. carteri was able to reduce the establishment of the biofilm formed by P. aeruginosa and could serve as a prominent source of natural antifouling agents.

Michael Addition Reaction between Dehydroalanines and Phosphites Enabled the Introduction of Phosphonates into Oligopeptides.

A method for introducing a range of phosphonates into oligopeptides through a Michael addition reaction between dehydroalanine and phosphite is presented. The method offers a mild, cheap, and straightforward approach to peptide phosphorylation that has potential applications in chemical biology and medicinal chemistry. Moreover, the introduction of a phosphonate group into short antibacterial peptides is described to demonstrate its utility, leading to the discovery of phosphonated antibacterial peptides with potent broad-spectrum antibacterial activity.

Heterologous expression of frog antimicrobial peptide Odorranain-C1 in Pichia pastoris: Biological characteristics and its application in food preservation

To reduce food spoilage and deterioration caused by microbial contamination, antimicrobial peptides (AMPs) have gradually gained attention as a biological preservative. Odorranain-C1 is an α-helical cationic antimicrobial peptide extracted from the skin of frogs with broad-spectrum antimicrobial activity. In this study, we achieved the expression of Odorranain-C1 in Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) by employing DNA recombination technology. The recombinant Odorranain-C1 showed broad-spectrum antibacterial activity and displayed a minimum inhibitory concentration within the range of 8–12 μg.mL-1. Meanwhile, Odorranain-C1 exhibited superior stability and lower hemolytic activity. Mechanistically, Odorranain-C1 disrupted the bacterial membrane's integrity, ultimately causing membrane rupture and subsequent cell death. In tilapia fillets preservation, Odorranain-C1 inhibited the total colony growth and pH variations, while also reducing the production of total volatile basic nitrogen (TVB-N) and thiobarbituric acid (TBA). In conclusion, these studies demonstrated the efficient recombinant expression of Odorranain-C1 in P. pastoris, highlighting its promising utilization in food preservation.

Dental Caries Management with Antibacterial Silver-Doped Prussian Blue Hydrogel by the Combined Effects of Photothermal Response and Ion Discharge.

Caries is a destructive condition caused by bacterial infection that affects the hard tissues of the teeth, significantly reducing the quality of life for individuals. Photothermal therapy (PTT) offers a noninvasive and painless treatment for caries, but the use of unsafe laser irradiance limits its application. To address this challenge, we prepared nanoparticles of silver ion-doped Prussian blue (AgPB), which was encased within cationic guar gum (CG) to form the antibacterial PTT hydrogel CG-AgPB with a photothermal conversion efficiency of 34.4%. When exposed to an 808 nm laser at a power density of 0.4 W/cm2, the hydrogel readily reached a temperature of over 50 °C in just 3 min, synchronized by the discharge of Ag+ ions from the interstitial sites of AgPB crystals, resulting in broad-spectrum and synergistic antibacterial activities (>99%) against individual oral pathogens (Streptococcus sanguinis, Streptococcus mutans, and Streptococcus sobrinus) and pathogen-induced biofilms. In vivo, CG-AgPB-mediated PTT demonstrated a capability to profoundly reduce the terminal number of cariogenic bacteria to below 1% in a rat model of caries. Given the outstanding biocompatibility, injectability, and flushability, this CG-AgPB hydrogel may hold promise as a next-generation oral hygiene adjunct for caries management in a clinical setting.

Secondary Structure Stabilization of Macrocyclic Antimicrobial Peptides via Cross-Link Swapping.

Lactam cross-links have been employed to stabilize the helical secondary structure and enhance the activity and physiological stability of antimicrobial peptides; however, stabilization of β-sheets via lactamization has not been observed. In the present study, lactams between the side chains of C- and N-terminal residues have been used to stabilize the β-sheet conformation in a short ten-residue analogue of chicken angiogenin-4. Designed using a combination of molecular dynamics simulations and Markov state models, the lactam cross-linked peptides are shown to adopt stabilized β-sheet conformations consistent with simulated structures. Replacement of the peptide side-chain Cys-Cys disulfide by a lactam cross-link enhanced the broad-spectrum antibacterial activity compared to the parent peptide and exhibited greater propensity to induce proinflammatory activity in macrophages. The combination of molecular simulations and conformational and biological analyses of the synthetic peptides provides a useful paradigm for the rational design of therapeutically active peptides with constrained β-sheet structures.

Novel biaryloxazolidinone derivatives with broad-spectrum antibacterial activity, favorable drug-like profiles and in vivo efficacy against linezolid-resistant Staphylococcusaureus

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S. aureus, multidrug resistant S. aureus and Enterococcus faecalis were evaluated. Remarkably, compound 8b was identified with potent antibacterial activity against S. aureus (MIC=0.06μg/mL), MSSA (MIC=0.125μg/mL), MRSA (MIC=0.06μg/mL), LRSA (MIC=0.125μg/mL) and LREFa (MIC=0.5μg/mL). Compound 8b was demonstrated as a promising candidate through druglikeness evaluation including metabolism in microsomes and plasma, Caco-2cell permeability, plasma protein binding, cytotoxicity, and inhibition of CYP450 and human monoamine oxidase. Notably, compound 8b displayed excellent PK profile with appropriate T1/2 of 1.49h, high peak plasma concentration (Cmax=2320ng/mL), high plasma exposure (AUC0-t=8310hng/mL), and superior oral bioavailability (F=68.1%) in Sprague-Dawley rats. Ultimately, in vivo efficacy of compound 8b in a mouse model of LRSA systemic infection was also demonstrated. Taken together, compound 8b represents a promising drug candidate for the treatment of linezolid-resistant Gram-positive bacterial strains infection.

Testing of Anti-EMT, Anti-Inflammatory and Antibacterial Activities of 2',4'-Dimethoxychalcone.

Chalcone (1,3-diaryl-2-propen-1-one) is an α, β-unsaturated ketone that serves as an active constituent or precursor of numerous natural substances, exhibiting a broad spectrum of pharmacological effects. In this study, the classical Claisen-Schmidt condensation method was used to synthesize the chalcone derivative 2',4'-dimethoxychalcone (DTC) and evaluate its pharmacological activity. By upregulating the expression of the epithelial cell marker E-cadherin and downregulating the expression of the mesenchymal cell marker vimentin, DTC was found to inhibit transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) process in A549 cells, maintaining the cells' epithelial-like morphology and reducing the ability of the cells to migrate. Additionally, DTC demonstrated the ability to decrease the expression levels of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in RAW264.7 cells, suggesting a possible anti-inflammatory effect. Furthermore, DTC was found to exhibit bacteriostatic activity against Staphylococcus aureus (S. aureus), Proteus vulgaris (P. vulgaris), methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans (C. albicans), indicating that this chemical may possess broad-spectrum antibacterial activity.

Discovery and Structure-Activity Relationship of Cadazolid: A First-In-Class Quinoxolidinone Antibiotic for the Treatment of Clostridioides difficile Infection.

Clostridioides difficile (C. difficile) is one of the leading causes of healthcare-associated infections worldwide. The increasing incidence of strains resistant to currently available therapies highlights the need for alternative treatment options with a novel mode of action. Oxazolidinones that are connected to a quinolone moiety with a pyrrolidine linker, such as compound 1, are reported to exhibit potent broadspectrum antibacterial activity. In an effort to optimize this class of compounds for the treatment of C. difficile infection (CDI), we have identified cadazolid (9), a first-in-class quinoxolidinone antibiotic, which is a potent inhibitor of C. difficile protein synthesis. In order to achieve narrow-spectrum coverage of clinically most relevant strains without affecting the gut microbiota, an emphasis was placed on abolishing activity against commensals of the intestinal microbiome while retaining good coverage of pathogenic C. difficile, including hypervirulent and epidemic strains.

Highly Efficient Self-Assembly of Heterometallic [2]Catenanes and Cyclic Bis[2]catenanes via Orthogonal Metal-Coordination Interactions.

Although catenated cages have been widely constructed due to their unique and elegant topological structures, cyclic catenanes formed by the connection of multiple catenane units have been rarely reported. Herein, based on the orthogonal metal-coordination-driven self-assembly, we prepare a series of heterometallic [2]catenanes and cyclic bis[2]catenanes, whose structures are clearly evidenced by single-crystal X-ray analysis. Owing to the multiple positively charged nature, as well as the potential synergistic effect of the Cu(I) and Pt(II) metal ions, the cyclic bis[2]catenanes display broad-spectrum antibacterial activity. This work not only provides an efficient strategy for the construction of heterometallic [2]catenanes and cyclic bis[2]catenanes but also explores their applications as superior antibacterial agents, which will promote the construction of advanced supramolecular structures for biomedical applications.

Antibacterial Activity by Diffusion and Dilution Methods of Liquid Smoke Cocos nucifera L.

Introduction: Liquid smoke is a product that obtained industrially from coconut shell through pyrolysis process at 400°C for 2,5 hours and redestillation to obtain grade 1 liquid smoke. Coconut shell liquid smoke contains chemical compounds, namely phenol, which has been researched to act as a disinfectant that has broad spectrum antibacterial activity against gram positive and gram negative bacteria. Method: This study aims to determine the potential of cocos nucifera L. liquid smoke as an antibacterial against Staphylococcus aureus and Methicillin-resistant staphylococcus aureus (MRSA) bacteria using diffusion and dilution methods. The concentrations used were 100%, 80%, 60%, 40%, 35%, 30%, 15%, 10%, 7%, 5%. As positive control was used Tetracycline 25 ppm. Results: Liquid smoke has the potential to inhibit the growth of both bacteria. The effective concentration to inhibit the growth of S. aureus at 40% concentration and MRSA at 80% concentration. The MIC value of liquid smoke against S. aureus is 0,78%, while on MRSA 3,12%. The MBC of S. aureus and MRSA bacteria at concentrations 1,56% and 6,25%. Staphylococcus aureus has higher sensitivity to Cocos nucifera L. grade 1 liquid smoke than MRSA bacteria. Conclusion: Cocos nucifera L. liquid smoke has antibacterial activity against Staphylococcus aureus and MRSA at effective concentrations of 40% and 80%. The MIC value of S. aureus is 0,78%, while MRSA is 3,12%. The MBC of S. aureus and MRSA bacteria at concentrations 1,56% and 6,25%. Keywords: antibacterial, liquid smoke, phenol, Cocos nucifera L.

Systematic alanine and stapling mutational analysis of antimicrobial peptide Chem-KVL

Chem-KVL is a tandem repeating peptide, with 14 amino acids that was modified based on a short peptide from a fragment of the human host defense protein chemerin. Chem-KVL increases cationicity and hydrophobicity and shows broad-spectrum antibacterial activity. To determine the molecular determinants of Chem-KVL and whether staple-modified Chem-KVL would improve antibacterial activity and protease stability or decrease cytotoxicity, we combined alanine and stapling scanning, and designed a series of alanine and staple-derived Chem-KVL peptides, termed Chem-A1 to Chem-A14 and SCL-1 to SCL-7. We next examined their antibacterial activity against several gram-positive and gram-negative bacteria, their proteolytic stability, and their cytotoxicity. Ala scanning of Chem-KVL suggested that both the positively charged residues (Lys and Arg) and the hydrophobic residues (Lue and Val) were critical for the antibacterial activities of Chem-KVL peptide. Of note, Chem-A4 was able to remarkably inhibit the growth of gram-positive and gram-negative bacteria when compared to the original peptide. And the antibacterial activities of stapled SCL-4 and SCL-7 were several times higher than those of the linear peptide against gram-positive and gram-negative bacteria. Stapling modification of peptides resulted in increased helicity and protein stability when compared with the linear peptide. These stapled peptides, especially SCL-4 and SCL-7, may serve as the leading compounds for further optimization and antimicrobial therapy.

Acorus calamus L. rhizome extract and its bioactive fraction exhibits antibacterial effect by modulating membrane permeability and fatty acid composition.

Ethnopharmacological relevanceIndia's ancient texts, the Charak Samhita and Sushruta Samhita, make reference to the traditional medicinal usage of Acorus calamus L. In India and China, it has long been used to cure stomach aches, cuts, diarrhea, and skin conditions. This ability of the rhizome is attributed to its antimicrobial properties. Research studies to date have shown its antimicrobial properties. However, scientific evidence on its mode of action is still lacking. Aim of the studyAcorus calamus L. rhizome extract and its bioactive fraction exhibits antibacterial effect by modulating membrane permeability and fatty acid composition. Material and methodThe secondary metabolites in the rhizome of A. calamus L. were extracted in hexane using Soxhlet apparatus. The ability of the extract to inhibit multidrug resistant bacterial isolates, namely Bacillus cereus, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were evaluated using checkerboard assay. Further, the extract was purified using thin layer chromatography, gravity column chromatography, and combiflash chromatography. Structure elucidation of the active compound was done using GC-MS, FT-IR, and UV–Vis spectral scan. The mode of action of the bioactive fraction was determined. Bacterial membrane damage was analyzed using SEM, membrane permeability was determined using SYBR green I and PI dye, leakage of cytoplasmic contents were analyzed using Bradford assay and Fehling’s reagent. The ability to inhibit efflux pump of A. baumannii was determined using EtBr accumulation assay and β-lactamase inhibition was analyzed using nitrocefin as substrate. Also, the biofilm inhibition of B. cereus was determined using crystal violet dye. Moreover, the effect of the bioactive fraction on the fatty acid profile of the bacterial membrane was determined by GC-FAME analysis using 37 component FAME mix as standard. ResultsAcorus calamus L. rhizome hexane extract (AC-R-H) demonstrated broad-spectrum antibacterial activity against all the isolates tested. AC-R-H extract also significantly reduced the MIC of ampicillin against all tested bacteria, indicating its bacterial resistance modulating properties. The assay guided purification determined Asarone as the major compound present in the bioactive fraction (S-III-BAF). S-III-BAF was found to reduce the MIC of ampicillin against Escherichia coli (100–25 mg/mL), Pseudomonas aeruginosa (15–3.25 mg/mL), Acinetobacter baumannii (12.5–1.56 mg/ml), and Bacillus cereus (10–1.25 mg/mL). Further, it recorded synergistic activity with ampicillin against B. cereus (FICI = 0.365), P. aeruginosa (FICI = 0.456), and A. baumannii (FICI = 0.245). The mode of action of S-III-BAF can be attributed to its ability to disturb the membrane integrity, enhance membrane permeability, reduce biofilm formation, and possibly alter the fatty acid composition of the bacterial cell membranes. ConclusionThe bioactive fraction of AC-R-H extract containing Asarone as the active compound showed antibacterial activity and synergistic interactions with ampicillin against the tested bacterial isolates. Such activity can be attributed to the modulation of fatty acids present in bacterial membranes, which enhances membrane permeability and causes membrane damage.

AMP-Mimetic Antimicrobial Polymer-Involved Synergic Therapy with Various Coagents for Improved Efficiency.

The misuse of antibiotics contributes to the emergence of multidrug-resistant (MDR) bacteria. Infections caused by MDR bacteria are rapidly evolving into a significant threat to global healthcare due to the lack of effective and safe treatments. Antimicrobial peptides (AMPs) with broad-spectrum antibacterial activity kill bacteria generally through a membrane disruption mechanism; hence, they tend not to induce resistance readily. However, AMPs exhibit disadvantages, such as high cost and susceptibility to proteolytic degradation, which limit their clinical application. AMP-mimetic antimicrobial polymers, with low cost, stability to proteolysis, broad-spectrum antimicrobial activity, negligible antimicrobial resistance, and rapid bactericidal effect, have received extensive attention as a new type of antibacterial drugs. Lately, AMP-mimetic polymer-involved synergic therapy provides a superior alternative to combat MDR bacteria by distinct mechanisms. In this Review, we summarize the AMP-mimetic antimicrobial polymers involved in synergic therapy, particularly focusing on the different combinations between the polymers with commercially available antimicrobials, organic small molecule photosensitizers, inorganic nanomaterials, and nitric oxide.

Development of a Selective and Stable Antimicrobial Peptide.

Antimicrobial peptides (AMPs) are presented as potential scaffolds for antibiotic development due to their desirable qualities including broad-spectrum activity, rapid action, and general lack of susceptibility to current resistance mechanisms. However, they often lose antibacterial activity under physiological conditions and/or display mammalian cell toxicity, which limits their potential use. Identification of AMPs that overcome these barriers will help develop rules for how this antibacterial class can be developed to treat infection. Here we describe the development of our novel synthetic AMP, from discovery through in vivo application. Our evolved AMP, DTr18-dab, has broad-spectrum antibacterial activity and is nonhemolytic. It is active against planktonic bacteria and biofilm, is unaffected by colistin resistance, and importantly is active in both human serum and a Galleria mellonella infection model. Several modifications, including the incorporation of noncanonical amino acids, were used to arrive at this robust sequence. We observed that the impact on antibacterial activity with noncanonical amino acids was dependent on assay conditions and therefore not entirely predictable. Overall, our results demonstrate how a relatively weak lead can be developed into a robust AMP with qualities important for potential therapeutic translation.

Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii

Multidrug-resistant (MDR) pathogens are a rising global health worry that imposes an urgent need for the discovery of novel antibiotics particularly those of natural origin. In this context, we aimed to use the metagenomic nanopore sequence analysis of soil microbiota coupled with the conventional phenotypic screening and genomic analysis for identifying the antimicrobial metabolites produced by promising soil isolate(s). In this study, whole metagenome analysis of the soil sample(s) was performed using MinION™ (Oxford Nanopore Technologies). Aligning and analysis of sequences for probable secondary metabolite gene clusters were extracted and analyzed using the antiSMASH version 2 and DeepBGC. Results of the metagenomic analysis showed the most abundant taxa were Bifidobacterium, Burkholderia, and Nocardiaceae (99.21%, followed by Sphingomonadaceae (82.03%) and B. haynesii (34%). Phenotypic screening of the respective soil samples has resulted in a promising Bacillus isolate that exhibited broad-spectrum antibacterial activities against various MDR pathogens. It was identified using microscopical, cultural, and molecular methods as Bacillus (B.) haynesii isolate MZ922052. The secondary metabolite gene analysis revealed the conservation of seven biosynthetic gene clusters of antibacterial metabolites namely, siderophore lichenicidin VK21-A1/A2 (95% identity), lichenysin (100%), fengycin (53%), terpenes (100%), bacteriocin (100%), Lasso peptide (95%) and bacillibactin (53%). In conclusion, metagenomic nanopore sequence analysis of soil samples coupled with conventional screening helped identify B. haynesii isolate MZ922052 harboring seven biosynthetic gene clusters of promising antimicrobial metabolites. This is the first report for identifying the bacteriocin, lichenysin, and fengycin biosynthetic gene clusters in B. haynesii MZ922052.

Nonphytotoxic and pH-responsive ZnO-ZIF‑8 loaded with honokiol as a “nanoweapon” effectively controls the soil-borne bacterial pathogen Ralstonia solanacearum

The development of intelligently released and environmentally safe nanocarriers not only aligns with the sustainable agricultural strategy but also offers a potential solution for controlling severe soil-borne bacterial diseases. Herein, the core-shell structured nanocarrier loaded with honokiol bactericide (honokiol@ZnO-ZIF-8) was synthesized via a one-pot method for the targeted control of Ralstonia solanacearum, the causative agent of tobacco bacterial wilt disease. Results indicated that honokiol@ZnO-ZIF-8 nanoparticles induced bacterial cell membrane and DNA damage through the production of excessive reactive oxygen species (ROS), thereby reducing bacterial cell viability and ultimately leading to bacterial death. Additionally, the dissociation mechanism of the nanocarriers was elucidated for the first time through thermodynamic computational simulation. The nanocarriers dissociate primarily due to H+ attacking the N atom on imidazole, causing the rupture of the Zn-N bond under acidic conditions and at room temperature. Furthermore, honokiol@ZnO-ZIF-8 exhibited potent inhibitory effects against other prominent Solanaceae pathogenic bacteria (Pseudomonas syringae pv. tabaci), demonstrating its broad-spectrum antibacterial activity. Biosafety assessment results indicated that honokiol@ZnO-ZIF-8 exhibited non-phytotoxicity towards tobacco and tomato plants, with its predominant accumulation in the roots and no translocation to aboveground tissues within a short period. This study provides potential application value for the intelligent release of green pesticides. Environment implicationThe indiscriminate use of agrochemicals poses a significant threat to environmental, ecological security, and sustainable development. Slow-release pesticides offer a green and durable strategy for crop disease control. In this study, we developed a non-phytotoxic and pH-responsive honokiol@ZnO-ZIF-8 nano-bactericide based on the pathogenesis of Ralstonia solanacearum. Thermodynamic simulation revealed the dissociation mechanism of ZIF-8, with different acidity controlling the dissociation rate. This provides a theoretical basis for on-demand pesticide release while reducing residue in the. Our findings provide strong evidence for effective soil-borne bacterial disease control and on-demand pesticide release.

Triton X-100 enhanced antibacterial effect of photodynamic therapy against Enterococcus faecalis infection: an in vitro study

Photodynamic therapy (PDT) is an effective method for bacterial infection control in root canals of teeth with a broad-spectrum antibacterial activity. However, its application in root canal treatment is limited due to its inefficiency under hypoxic conditions and dentin staining. Triton X-100 (TX) shows great potential in enhancing the efficiency of antimicrobial agents through improving bacterial membrane permeability. The present study employed a combination of toluidine blue O (TB)-mediated PDT with TX to target the Enterococcus faecalis (E. faecalis), a bacterium with strong resistance to various antibacterial agents and mostly detected in infected root canals. PDT combined with TX showed enhanced antibacterial efficiency against both planktonic cells and biofilms of E. faecalis. At the same time, TX enhanced the antibacterial effect in dentinal tubules and reduced the incubation time. Mechanism studies revealed that TX improved reactive oxygen species (ROS) production through increasing the proportion of TB monomers. Additionally, increased membrane permeability and wettability were also observed. The findings demonstrated the PDT combined with TX could be used as a highly effective method for the root canal disinfection of teeth.

A novel antimicrobial peptide Spasin141-165 identified from Scylla paramamosain exhibiting protection against Aeromonas hydrophila infection

Aeromonas hydrophila is a widely distributed Gram-negative waterborne pathogen responsible for large-scale outbreaks of hemorrhagic septicemia in fish, causing severe economic losses to the global aquaculture industry. In view of few therapeutic drugs currently available for use in aquaculture and the emergence of multidrug-resistant A. hydrophila, there is an urgent need to develop new antimicrobial agents as an alternative to antibiotics. Antimicrobial peptides (AMPs) have strong antimicrobial effects and unique machanisms of action, and are not easy to induce bacterial resistance, making them an ideal alternative to antibiotics. In this study, we identified a new functional gene from marine crab Scylla paramamosain, named Spasin, which encodes a mature peptide of 240 amino acids and expressed widely in various tissues of crabs. Notably, a truncated peptide Spasin141–165 derived from Spasin, showed potent and broad-spectrum antibacterial and antifungal activity at minimum inhibitory concentrations (MICs) ranged from 0.75 μM–48 μM, which is a novel AMP. It effectively killed S. aureus and A. baumannii within 2 h and 90 min, respectively. Importantly, it is not toxic to HEK-293 T, RAW 264.7, and ZF4 cell lines. Mechanistic studies showed that addition of 8 μg mL−1 lipoteichoic acid or lipopolysaccharides decreased bacterial susceptibility to Spasin141–165. In addition, Spasin141–165 altered the permeability of the inner and outer cell membranes, and resulted in the release of ATP and the accumulation of intracellular reactive oxygen species. Notably, Spasin141–165 significantly increased the survival rate of zebrafish infected with A. hydrophila, redcued the bacterial load in the spleen, and effectively inhibited the expression of inflammation-associated factors (e.g., IL-1β, TNF-α, etc.). Taken together, Spasin141–165 is a potential antibacterial agent for the treatment of A. hydrophila infections in aquaculture and a promising antibiotic alternative.

Antibacterial, Phytochemical and Toxicological Activities of Garcinia kola Extracts against Multidrug Resistant Clinical Bacteria

Objective: The rise in multiple antibiotic resistant microorganisms has led to a decline in the efficacy of many antibiotics, prompting the investigation of alternative solutions such as medicinal plants. To tackle this concerning issue, this study was undertaken to evaluate the phytochemical composition, antibacterial activity, and toxicological characteristics of Garcinia kola extracts against multidrug-resistant bacteria commonly found in clinical settings. Material-Method: The cold maceration technique was employed to extract the root and leaf of Garcinia kola using water and methanol. The extracts were then subjected to phytochemical screening. To evaluate the extracts' potential to inhibit bacterial growth, five multidrug-resistant isolates were utilized in this study. Agar well assay was used to determine the zones of inhibition. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined using the broth macro dilution technique. Additionally, Brine shrimp lethality assay was conducted to determine the lethal concentration (LC50) of the extracts. The extracts were also combined for synergism. Results: The investigation found that the root extract in methanol had the highest yield at 25.58%. All four extracts contained ten out of the fourteen tested phytochemicals. The methanol leaf and root extracts exhibited the highest and lowest inhibition zones of 20mm and 9mm against Staphylococcus aureus, respectively. The MIC values ranged from 250 to 600 mg/ml, indicating broad-spectrum antibacterial activity. The cytotoxicity test showed a range of 33.03 to 126.3µg/mL for the aqueous and methanol extracts. Conclusion: Although Garcinia kola shows potential as a source of antibacterial compounds, caution should be exercised due to its toxic effects.