Broad-spectrum Antimicrobial Agents Research Articles

Enhanced Mechanical Strength and Sustained Drug Release in Carrier-Free Silver-Coordinated Anthraquinone Natural Antibacterial Anti-Inflammatory Hydrogel for Infectious Wound Healing.

The persistent challenge of healing infectious wounds and the rise of bacterial resistance represent significant hurdles in contemporary medicine. In this study, based on the natural small molecule drug Rhein self-assembly to form hydrogels and coordinate assembly with silver ions (Ag+), a sustained-release carrier-free hydrogel with compact structure is constructed to promote the repair of bacterial-infected wounds. As a broad-spectrum antimicrobial agent, Ag+ can avoid the problem of bacterial resistance caused by the abuse of traditional antibiotics. In addition, due to the slow-release properties of Rhein hydrogel, continuous effective concentration of Ag+ at the wound site can be ensured. The assembly of Ag+ and Rhein makes the hydrogel system with enhanced mechanical stability. More importantly, it is found that Rhein effectively promotes skin tissue regeneration and wound healing by reprogramming M1 macrophages into M2 macrophages. Further mechanism studies show that Rhein realizes its powerful anti-inflammatory activity through NRF2/HO-1 activation and NF-κB inhibition. Thus, the hydrogel system combines the excellent antibacterial properties of Ag+ with the excellent anti-inflammatory and tissue regeneration ability of Rhein, providing a new strategy for wound management with dual roles.

Identifying and characterization of novel broad-spectrum bacteriocins from the Shanxi aged vinegar microbiome: Machine learning, molecular simulation, and activity validation

Shanxi aged vinegar microbiome encodes a wide variety of bacteriocins. The aim of this study was to mine, screen and characterize novel broad-spectrum bacteriocins from the large-scale microbiome data of Shanxi aged vinegar through machine learning, molecular simulation and activity validation. A total of 158 potential bacteriocins were innovatively mined from 117,552 representative genes based on metatranscriptomic information from the Shanxi aged vinegar microbiome using machine learning techniques and 12 microorganisms were identified to secrete bacteriocins at the genus level. Subsequently, employing AlphaFold2 structure prediction and molecular dynamics simulations, eight bacteriocins with high stability were further screened, and all of them were confirmed to have bacteriostatic activity by the Escherichia coli BL21 expression system. Then, gene_386319 (named LAB-3) and gene_403047 (named LAB-4) with the strongest antibacterial activities were purified by two-step methods and analyzed by mass spectrometry. The two bacteriocins have broad-spectrum antimicrobial activity with minimum inhibitory concentration values of 6.79 μg/mL-15.31 μg/mL against Staphylococcus aureus and Escherichia coli. Furthermore, molecular docking analysis indicated that LAB-3 and LAB-4 could interact with dihydrofolate reductase through hydrogen bonds, salt-bridge forces and hydrophobic forces. These findings suggested that the two bacteriocins could be considered as promising broad-spectrum antimicrobial agents.

Design and synthesis of new quinazolinone derivatives: investigation of antimicrobial and biofilm inhibition effects.

New quinazolin-4-ones 9-32 were synthesized in an attempt to overcome the life-threatening antibiotic resistance phenomenon. The antimicrobial screening revealed that compounds 9, 15, 16, 18, 19, 20 and 29 are the most broad spectrum antimicrobial agents in this study with safe profile on human cell lines. Additionally, compounds 19 and 20 inhibited biofilm formation in Pseudomonas aeruginosa, which is regulated by quorum sensing system, at sub-minimum inhibitory concentrations (sub-MICs) with IC50 values 3.55 and 6.86µM, respectively. By assessing other pseudomonal virulence factors suppression, it was found that compound 20 decreased cell surface hydrophobicity compromising bacterial cells adhesion, while both compounds 19 and 20 curtailed the exopolysaccharide production which constitutes the major component of the matrix binding biofilm components together. Also, at sub-MICs Pseudomonas cells twitching motility was impeded by compounds 19 and 20, a trait which augments the cells pathogenicity and invasion potential. Molecular docking study was performed to further evaluate the binding mode of candidates 19 and 20 as inhibitors of P. aeruginosa quorum sensing transcriptional regulator PqsR. The achieved results demonstrate that both compounds bear promising potential for discovering new anti-biofilm and quorum quenching agents against Pseudomonas aeruginosa without triggering resistance mechanisms as the normal bacterial life cycle is not disturbed.

Quantum biochemical analysis of the TtgR regulator and effectors

The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs. These advances are crucial in the ongoing fight against rising antimicrobial drug resistance, providing hope for a future where healthcare-associated infections can be more beneficially treated.

Pharmacokinetics of Enrofloxacin in Plasma, Urine, and Feces of Donkey (Equus asinus) after a Single Intragastric Administration.

Enrofloxacin is a broad-spectrum antimicrobial agent, but the study of its pharmacokinetics/pharmacodynamics (PKs/PDs) in donkeys is rarely reported. The present study aimed to investigate the pharmacokinetics of enrofloxacin administered intragastrically, and to study the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in plasma, urine, and feces, and the PK/PD parameters were investigated to provide a rationale for enrofloxacin treatment in donkeys. A total of five healthy donkeys were selected for intragastric administration of 7.5 mg·kg-1 BW of enrofloxacin by gavage, and blood, urine, and fecal samples were collected. The results showed that the elimination half-life of plasma enrofloxacin was 11.40 ± 6.40 h, Tmax was 0.55 ± 0.12 h, Cmax was 2.46 ± 0.14 mg·L-1, AUC0-∞ was 10.30 ± 3.37 mg·L-1·h, and mean residence time (MRT) was 7.88 ± 1.26 h. The Tmax of plasma ciprofloxacin was 0.52 ± 0.08 h, Cmax was 0.14 ± 0.03 mg·L-1, and AUC0-∞ was 0.24 ± 0.16 mg·L-1·h. Urinary Cmax was 38.18 ± 8.56 mg·L-1 for enrofloxacin and 15.94 ± 4.15 mg·L-1 for ciprofloxacin. The total enrofloxacin and ciprofloxacin recovered amount in urine was 7.09 ± 2.55% of the dose for 144 h after dosing. The total enrofloxacin and ciprofloxacin recovered amount in feces was 25.73 ± 10.34% of the dose for 144 h after dosing. PK/PD parameters were also examined in this study, based on published MICs. In conclusion, 7.5 mg/kg BW of enrofloxacin administered intragastrically to donkeys was rapidly absorbed, widely distributed, and slowly eliminated in their bodies, and was predicted to be effective against bacteria with MICs < 0.25 mg·L-1.

Naphthylisoquinoline alkaloids: novel agents against the causative pathogens of eumycetoma and actinomycetoma-en route to broad-spectrum antimycetomal drugs.

Mycetoma is a devastating neglected tropical infection of the subcutaneous tissues. It is caused by fungal and bacterial pathogens recognized as eumycetoma and actinomycetoma, respectively. Mycetoma treatment involves diagnosing the causative microorganism as a prerequisite to prescribing a proper medication. Current therapy of fungal eumycetoma causative agents, such as Madurella mycetomatis, consists of long-term antifungal medication with itraconazole followed by surgery, yet with usually unsatisfactory clinical outcomes. Actinomycetoma, on the contrary, usually responds to treatment with co-trimoxazole and amikacin. Therefore, there is a pressing need to discover novel broad-spectrum antimicrobial agents to circumvent the time-consuming and costly diagnosis. Using the resazurin assay, a series of 23 naphthylisoquinoline (NIQ) alkaloids and related naphthoquinones were subjected to in vitro screening against two fungal strains of M. mycetomatis and three bacterial strains of Actinomadura madurae and A. syzygii. Seven NIQs, mostly dimers, showed promising in vitro activities against at least one strain of the mycetoma-causative pathogens, while the naphthoquinones did not show any activity. A synthetic NIQ dimer, 8,8'''-O,O-dimethylmichellamine A (18), inhibited all tested fungal and bacterial strains (IC50 = 2.81-12.07 µg/mL). One of the dimeric NIQs, michellamine B (14), inhibited a strain of M. mycetomatis and significantly enhanced the survival rate of Galleria mellonella larvae infected with M. mycetomatis at concentrations of 1 and 4 µg/mL, without being toxic to the uninfected larvae. As a result, broad-spectrum dimeric NIQs like 14 and 18 with antimicrobial activity are considered hit compounds that could be worth further optimization to develop novel lead antimycetomal agents.

Evaluation of Fusobacterium nucleatum Enoyl-ACP Reductase (FabK) as a Narrow-Spectrum Drug Target.

Fusobacterium nucleatum, a pathobiont inhabiting the oral cavity, contributes to opportunistic diseases, such as periodontal diseases and gastrointestinal cancers, which involve microbiota imbalance. Broad-spectrum antimicrobial agents, while effective against F. nucleatum infections, can exacerbate dysbiosis. This necessitates the discovery of more targeted narrow-spectrum antimicrobial agents. We therefore investigated the potential for the fusobacterial enoyl-ACP reductase II (ENR II) isoenzyme FnFabK (C4N14_ 04250) as a narrow-spectrum drug target. ENRs catalyze the rate-limiting step in the bacterial fatty acid synthesis pathway. Bioinformatics revealed that of the four distinct bacterial ENR isoforms, F. nucleatum specifically encodes FnFabK. Genetic studies revealed that fabK was indispensable for F. nucleatum growth, as the gene could not be deleted, and silencing of its mRNA inhibited growth under the test conditions. Remarkably, exogenous fatty acids failed to rescue growth inhibition caused by the silencing of fabK. Screening of synthetic phenylimidazole analogues of a known FabK inhibitor identified an inhibitor (i.e., 681) of FnFabK enzymatic activity and F. nucleatum growth, with an IC50 of 2.1 μM (1.0 μg/mL) and a MIC of 0.4 μg/mL, respectively. Exogenous fatty acids did not attenuate the activity of 681 against F. nucleatum. Furthermore, FnFabK was confirmed as the intracellular target of 681 based on the overexpression of FnFabK shifting MICs and 681-resistant mutants having amino acid substitutions in FnFabK or mutations in other genetic loci affecting fatty acid biosynthesis. 681 had minimal activity against a range of commensal flora, and it was less active against streptococci in physiologic fatty acids. Taken together, FnFabK is an essential enzyme that is amenable to drug targeting for the discovery and development of narrow-spectrum antimicrobial agents.

Synthesis and evaluation of novel ring-conjugated coumarins as biosafe broad-spectrum antimicrobial candidates

This study presents, for the first time, the synthesis of innovative conjugates identified as a five-membered ring integrating three heteroatoms linked linearly to the coumarin framework. Seven conjugates, comprising combinations of 1,3,2-dioxathiole-2-oxide and coumarin derivatives, were made via a three-stage synthetic procedure originating from benzene 1,2,4-triole. Spectroscopic methodologies, encompassing 1H-NMR, 13C-NMR, and FTIR, were utilized to validate the structural frameworks of the synthesized conjugates. Their capacity in the biomedicine field to act as broad-spectrum antimicrobial agents was evaluated. Furthermore, the biosafety and in silico pharmacokinetic characteristics of the conjugates were also examined. Six pathogenic aerobic bacteriomers, three anaerobic bacteriomers, and two fungiomers were utilized to investigate the broad-spectrum antimicrobial activity of the conjugates. On the other hand, three non-pathogenic bacteriomers were employed to reveal the biosafety profiles of the synthesized conjugates. Finally, two web-based programs were utilized to unveil the pharmacokinetic profiles of the title conjugates. The authors outlined four principal outcomes drawn from the extracted results. The conjugation between 1,3,2-dioxathiole-2-oxide and coumarin derivatives demonstrates biosafety and broad-spectrum antimicrobial implications. Conjugate DOTC5 displayed potent antibacterial activity against the tested aerobic bacteriomers, showing a potency comparable to that of the reference drug. Conjugate DOTC1 demonstrated strong antifungal activity exceeding that of the standard used. The synthesized conjugates, particularly DOTC5, displayed interesting biosafety profiles against the non-pathogenic bacteriomers. It concluded that the conjugates DOTC5 and DOTC1 exhibit the potential to function as valuable scaffolds for developing novel medications with biosafe, broad-spectrum antimicrobial activities in the foreseeable future.

Synthesis of narrow-spectrum anti-mycobacterial molecules without effect on the diversity of gut microbiota in mice based on the structure of rifampicin

Rifampicin (RIF) is a broad-spectrum antimicrobial agent that is also a first-line drug for treating tuberculosis (TB). Based on the naphthyl ring structure of RIF this study synthesized 16 narrow-spectrum antimicrobial molecules that were specifically anti-Mycobacterium tuberculosis (Mtb). The most potent candidate was 2-((6-hydroxynaphthalen-2-yl) methylene) hydrazine-1-carbothioamide (compound 3c) with minimum inhibitory concentration (MIC) of 1 μg/mL against Mtb. Synergistic anti-Mtb test indicated that none of the combinations of 3c with the major anti-TB drugs are antagonistic. Consistent with RIF, compound 3c induced large amounts of reactive oxygen radicals (ROS) in the cells of Mtb. The killing kinetics of compound 3c and RIF are very similar. Furthermore, molecular docking showed that compound 3c was able to access the RIF binding pocket of the β subunit of Mtb RNA polymerase (RNAP). Experiments in mice showed that compound 3c increased the variety of intestinal flora in mice, while RIF significantly decreased the diversity of intestinal flora in mice. In addition, compound 3c is non-toxic to animal cells with a selection index (SI) much more than 10. The evidence from this study suggests that the further development of 3c could contribute to the development of novel drug for TB treatment.

Unlocking nature's potential: Novel isomagnolone analogues as broad-spectrum antimicrobial agents for plant disease control

In an effort to develop novel, less toxic, and effective controls for plant diseases, we aimed to identify derivatives of the natural product isomagnolone with antimicrobial activity. We established a facile method for the synthesis of isomagnolone and its isomer Ⅱ, and prepared a series of novel isomagnolone analogues bearing N-(1,3-thiazol-2-yl)amides Ⅲ1–30. The structures of Ⅲ1–30 were determined by IR, 1H NMR, 13C NMR, and ESI-MS. Among them, compounds Ⅲ24 and Ⅲ26 exhibited potent antifungal activity against four fungi with EC50 values substantially lower than that of the positive control, hymexazol. Additionally, the antibacterial results showed that Ⅲ20 and Ⅲ22 displayed more potent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo) with EC50 values of 12.6 and 10.3 ​μg/mL, respectively, approximately 2-fold lower than that of the positive control, thiodiazole copper (EC50: 24.0 ​μg/mL). Structure-activity relationships suggested that the antifungal activity of title isomagnolone analogues was favored when the substituent (R) was pyridyl or the 2-chloro-3-pyridyl group. Mechanism of action studies revealed that Ⅲ22 could disrupt bacterial membranes, thus resulting in cell death. Furthermore, the potent compounds Ⅲ20, Ⅲ22, Ⅲ24, and Ⅲ26 showed low toxicity against the human hepatocyte cell line (LO2). Given these results, these isomagnolone analogues bearing N-(1,3-thiazol-2-yl)amides are promising antimicrobials against phytopathogenic fungi and bacteria for controlling plant diseases.

Safety and efficacy of McCarey-Kaufman medium supplemented with colistin (polymyxin E) and amphotericin B in inhibiting the multidrug-resistant Pseudomonas aeruginosa using an ex vivo donor corneal infection model.

This study aimed to evaluate the efficacy and safety of McCarey-Kaufman (MK) medium supplemented with colistin and amphotericin B in inhibiting the growth of multidrug-resistant Pseudomonas (P.) aeruginosa , using an ex vivo experimental model with human donor corneas. Cadaveric human corneas deemed unsuitable for corneal transplantation were obtained, and MK media were supplemented with colistin and amphotericin B. Multidrug-resistant P. aeruginosa was cultured and used to infect the human donor corneas ex vivo . Infected corneas were placed in the MK media with additional antibiotics (colistin and amphotericin B) and the standard MK media, which served as the control arm for comparison. Corneal opacity due to infiltration and quantitative analysis of colony-forming units (CFUs) were assessed. The viability of the corneal endothelium was assessed using trypan blue staining. Corneas incubated in MK media supplemented with additional antibiotics showed less corneal opacification compared with those in standard MK media at both 48- and 96-hour (hr) time points. Quantitative analysis revealed a lower bacterial load and a significant reduction in CFU in the corneas incubated in MK media with additional antibiotics compared with the control group. At 48 hrs, there was 84% ( P value = 0.024) reduction in bacterial load, and at 96 hr, a 53% ( P value = 0.016) reduction was observed in comparison with those placed in standard MK media. The trypan blue staining tests revealed that the extent of endothelial cell loss in corneas incubated in supplemented MK media was comparable to the ones in standard MK media. The addition of colistin and amphotericin B to MK media demonstrated efficacy in inhibiting the growth of multidrug-resistant P. aeruginosa in an ex vivo cornea infection model. The supplemented media had no detrimental effect on the corneal endothelium. The findings suggest that supplementing the MK media with these broad-spectrum antimicrobial agents may help mitigate the risk of postoperative donor-related infection in the recipients by reducing and containing the load of microbial contamination in donor corneas.

Tiny but mighty: metal nanoparticles as effective antimicrobial agents for plant pathogen control.

Metal nanoparticles (MNPs) have gained significant attention in recent years for their potential use as effective antimicrobial agents for controlling plant pathogens. This review article summarizes the recent advances in the role of MNPs in the control of plant pathogens, focusing on their mechanisms of action, applications, and limitations. MNPs can act as a broad-spectrum antimicrobial agent against various plant pathogens, including bacteria, fungi, and viruses. Different types of MNPs, such as silver, copper, zinc, iron, and gold, have been studied for their antimicrobial properties. The unique physicochemical properties of MNPs, such as their small size, large surface area, and high reactivity, allow them to interact with plant pathogens at the molecular level, leading to disruption of the cell membrane, inhibition of cellular respiration, and generation of reactive oxygen species. The use of MNPs in plant pathogen control has several advantages, including their low toxicity, selectivity, and biodegradability. However, their effectiveness can be influenced by several factors, including the type of MNP, concentration, and mode of application. This review highlights the current state of knowledge on the use of MNPs in plant pathogen control and discusses the future prospects and challenges in the field. Overall, the review provides insight into the potential of MNPs as a promising alternative to conventional chemical agents for controlling plant pathogens.

Essential Oils from Azorean Cryptomeria japonica Female Cones at Different Developmental Stages: Variations in the Yields and Chemical Compositions

Cryptomeria japonica (Thunb. ex L.f.) D. Don (Cupressaceae) is widely cultivated in the Azores archipelago (Portugal) for landscaping and timber production, generating a huge amount of biomass residues. Among these, female cones (FC) emerge as a source of particularly valuable essential oils (EOs), namely, as promising broad-spectrum antimicrobial agents. However, phytochemical research on C. japonica FC EOs remains scarce. This study evaluated the EO yields and chemical compositions of immature and mature FC (IFC and MFC) from the same batch of Azorean C. japonica. IFC and MFC EOs, obtained via hydrodistillation, presented different yields (0.72% vs. 1.12% w/w, dry weight), and their composition, determined via gas chromatography/mass spectroscopy, revealed that the monoterpenes class was dominant (51.84% vs. 69.13%), followed by the sesquiterpenes (36.44% vs. 26.28%) and diterpenes (10.96% vs. 3.03%) classes. However, the correspondent oxygen-containing terpenes classes were 1.5–2.0 times higher in IFC. Thus, the maturation process revealed an increase in EO yield and α-pinene content (19.5% vs. 41.3%) but a decrease in other important bioactive terpenes/terpenoids (terpinen-4-ol, bornyl acetate, elemol, γ-eudesmol, phyllocladene, and nezukol) content. In conclusion, IFC and MFC EOs, due to their unique composition, may have differential commercial applications and, consequently, contribute to increasing the commercial potential of C. japonica’s EO industry.

Metagenomic analysis of hot spring soil for mining a novel thermostable enzybiotic.

The misuse and overuse of antibiotics have contributed to a rapid emergence of antibiotic-resistant bacterial pathogens. This global health threat underlines the urgent need for innovative and novel antimicrobials. Endolysins derived from bacteriophages or prophages constitute promising new antimicrobials (so-called enzybiotics), exhibiting the ability to break down bacterial peptidoglycan (PG). In the present work, metagenomic analysis of soil samples, collected from thermal springs, allowed the identification of a prophage-derived endolysin that belongs to the N-acetylmuramoyl-L-alanine amidase type 2 (NALAA-2) family and possesses a LysM (lysin motif) region as a cell wallbinding domain (CWBD). The enzyme (Ami1) was cloned and expressed in Escherichia coli, and its bactericidal and lytic activity was characterized. The results indicate that Ami1 exhibits strong bactericidal and antimicrobial activity against a broad range of bacterial pathogens, as well as against isolated peptidoglycan (PG). Among the examined bacterial pathogens, Ami1 showed highest bactericidal activity against Staphylococcus aureus sand Staphylococcus epidermidis cells. Thermostability analysis revealed a melting temperature of 64.2 ± 0.6°C. Overall, these findings support the potential that Ami1, as a broad spectrum antimicrobial agent, could be further assessed as enzybiotic for the effective treatment of bacterial infections. KEY POINTS: • Metagenomic analysis allowed the identification of a novel prophage endolysin • The endolysin belongs to type 2 amidase family with lysin motif region • The endolysin displays high thermostability and broad bactericidal spectrum.

VesiX cetylpyridinium chloride is rapidly bactericidal and reduces uropathogenic Escherichia coli bladder epithelial cell invasion in vitro.

When urinary tract infections (UTIs), which affect over 50% of women, become resistant to available antibiotic therapies dangerous complications like kidney infection and lethal sepsis can occur. New therapeutic paradigms are needed to expand our arsenal against these difficult to manage infections. Our study investigates VesiX, a Cetylpyridinium chloride (CPC)-based therapeutic, as a candidate broad-spectrum antimicrobial agent for use in bladder instillation therapy for antibiotic-resistant UTI. CPC is a cationic surfactant that is FDA-approved for use in mouthwashes and is used as a food additive but has not been extensively evaluated as a UTI therapeutic. Our study is the first to investigate its rapid bactericidal kinetics against diverse uropathogenic bacterial species isolated from postmenopausal women with recurrent UTI and host cytotoxicity. We also report that together with the FDA-approved bladder-instillation agent gentamicin, VesiX was able to significantly reduce intracellular populations of uropathogenic bacteria in cultured bladder epithelial cells.

Smart Nanofibrous Hydrogel Wound Dressings for Dynamic Infection Diagnosis and Control: Soft but Functionally Rigid.

Chronic wounds, such as burns and diabetic foot ulcers, pose significant challenges to global healthcare systems due to prolonged hospitalization and increased costs attributed to susceptibility to bacterial infections. The conventional use of antibiotic-loaded and metal-impregnated dressings exacerbates concerns related to multidrug resistance and skin argyrosis. In response to these challenges, our research introduces a unique approach utilizing antibiotic-free smart hydrogel wound dressings with integrated infection eradication and diagnostic capabilities. Electrospinning stands out as a method capable of producing hydrogel nanofibrous materials possessing favorable characteristics for treating wounds and detecting infections under conditions utilizing sustainable materials. In this study, innovative dressings are fabricated through electrospinning polycaprolactone (PCL)/gelatin (GEL) hybrid hydrogel nanofibers, incorporating pDA as a cross-linker, εPL as a broad-spectrum antimicrobial agent, and anthocyanin as a pH-responsive probe. The developed dressings demonstrate exceptional antioxidant (>90% radical scavenging) and antimicrobial properties (95-100% killing). The inclusion of polyphenols/flavonoids and εPL leads to absolute bacterial eradication, and in vitro assessments using HaCaT cells indicate increased cell proliferation, decreased reactive oxygen species (ROS) production, and enhanced cell viability (100% Cell viability). The dressings display notable alterations in color that correspond to different wound conditions. Specifically, they exhibit a red/violet hue under healthy wound conditions (pH 4-6.5) and a green/blue color under unhealthy wound conditions (pH > 6.5). These distinctive color changes provide valuable insights into the versatile applications of the dressings in the care and management of wounds. Our findings suggest that these antibiotic-free smart hydrogel wound dressings hold promise as an effective and sustainable solution for chronic wounds, providing simultaneous infection control and diagnostic monitoring. This research contributes to advancing the field of wound care, offering a potential paradigm shift in the development of next-generation wound dressings.

An adamantyl-caffeoyl-anilide exhibits broad-spectrum antibacterial activity by inhibiting FtsZ assembly and Z-ring formation

Several harmful bacteria have evolved resistance to conventional antibiotics due to their extensive usage. FtsZ, a principal bacterial cell division protein, is considered as an important drug target to combat resistance. We identified a caffeoyl anilide derivative, (E)-N-(4-(3-(3,4-dihydroxyphenyl)acryloyl)phenyl)-1-adamantylamide (compound 11) as a new antimicrobial agent targeting FtsZ. Compound 11 caused cell elongation in Mycobacterium smegmatis, Bacillus subtilis, and Escherichia coli cells, indicating that it inhibits cell partitioning. Compound 11 inhibited the assembly of Mycobacterium smegmatis FtsZ (MsFtsZ), forming short and thin filaments in vitro. Interestingly, the compound increased the rate of GTP hydrolysis of MsFtsZ. Compound 11 also impeded the assembly of Mycobacterium tuberculosis FtsZ. Fluorescence and absorption spectroscopic analysis suggested that compound 11 binds to MsFtsZ and produces conformational changes in FtsZ. The docking analysis indicated that the compound binds at the interdomain cleft of MsFtsZ. Further, it caused delocalization of the Z-ring in Mycobacterium smegmatis and Bacillus subtilis without affecting DNA segregation. Notably, compound 11 did not inhibit tubulin polymerization, the eukaryotic homolog of FtsZ, suggesting its specificity on bacteria. The evidence indicated that compound 11 exerts its antibacterial effect by impeding FtsZ assembly and has the potential to be developed as a broad-spectrum antimicrobial agent.

Phytochemical Contents and In Vitro Pathogenic Microbial Growth Inhibitory Activities of Acanthus montanus Root and Leaf Extracts

The study was directed at extraction, bioactivity analysis and ascertaining phytochemical composition of the leaf and root extracts of Acanthus montanus. Acanthus montanus (Acanthaceae family) is a shrub that is popularly grown in tropical countries of the world. The plant materials were harvested from Choba community in Rivers State, Nigeria. Extracts of Acanthus montanus (28.3, 19.45 and 25.5 g of n-hexane, ethylacetate and ethanol leaf extracts; and 3.45, 11.32 and 12.44 g of n-hexane, ethylacetate and ethanol root extracts respectively) were obtained through sequential maceration and were separately subjected to in vitro bioassay against a wide range of pathogenic microbes using the agar well diffusion method. Fifteen microorganisms were employed in the investigation, eight bacteria which included Salmonella typhi, Salmonella paratyphi, Pseudomonas aeruginosa, Shigella sonniea, Shigella dysentariae, Escherichia coli, Staphylococcus aureus, Staphylococcus pyogenes and seven fungi which included Candida albicans, Sacharomyces cerevisiae, Rhizopus eligastus, Aspergillus flavus, Aspergillus fumigates, Fusa equisetti and Aspergillus niger. The crude extracts exhibited high microbial growth inhibitory activities with zones of inhibition which ranged between 14 and 34 mm, though there was moderate (19 mm zone of inhibition), or no activity observed for the n-hexane leaf and root extracts. All test organisms were sensitive to the extracts. Standard analytical methods and Gas Chromatography - Flame Ionization Detector (GC-FID) were used for analysis and quantification of the phytochemicals present in the extracts. Major phytochemical contents of the leaf and root extracts included flavonoids (86% - 52.66%), alkaloids (10.66% - 3.25%) and other phenolic compounds (20.52% - 6.38%). In conclusion, the leaf and root extracts of Acanthus montanus are broad-spectrum antimicrobial agents also rich in flavonoids.

Klebsiella and Acinetobacter Isolated from Patients with Special Reference to Antibacterial Sensitivity and Biofilm Formation

Klebsiella pneumoniae and Acinetobacter baumannii are the most important Gram-negative opportunistic pathogen that cause infectious diseases as respiratory tract infection, urinary tract infection and bacteremia. With high multidrug resistance due to their ability to form biofilm in medical devices as endotracheal tube and catheter. The biofilms consisted of micro colonies coated in extracellular polysaccharide material. The biofilms were not killed by the tested antibiotics. Biofilm is primed for survival to external stressors. Biofilms are responsible for more than 65% of nosocomial infections and contribute to infections associated with medical devices. Using plants in infectious diseases as lemon balm (Melissa officinalis), garlic (Allium sativum) and tee tree (Melaleuca alternifolia). Garlic (Allium sativum) have positive effect on human health. Garlic (Allium sativum) is described as broad-spectrum antimicrobial agent. A total number of samples of 50 human sputum samples were used in this experiment. klebsiella pneumoniae was isolated from 35 out of 50 samples and Acinetobacter baumannii from 15 out of 50 samples. Formation of biofilm from isolated bacteria. Extraction of garlic and use it as antimicrobial. The result showed that most of isolates of Klebsiella pneumoniae and Acinetobacter baumannii were form biofilm in medical devices. Klebsiella pneumoniae and Acinetobacter baumannii biofilm were resistance to most antibiotics. Garlic (Allium sativum) has broad-spectrum antimicrobial agent and has ability to elimination biofilm.

Rhynchophorus ferrugineus larvae: A novel source for combating broad-spectrum bacterial and fungal infections.

Antimicrobial resistance is a growing concern due to the growth of antibiotic-resistant microorganisms, which makes it difficult to treat infection. Due to its broad-spectrum antimicrobial properties against a diverse array of bacteria, both Gram-positive and Gram-negative bacteria, and fungi, Rhynchophorus ferrugineus larval antimicrobial peptides (AMPs) have demonstrated potential as antimicrobial agents for the treatment of microbial infections and prevention of antibiotic resistance. This study emphasizes the unexplored mechanisms of action of R. ferrugineus larvae against microorganisms. Among the most widely discussed mechanisms is the effect of AMPs in larvae in response to a threat or infection. Modulation of immune-related genes in the intestine and phagocytic capacity of its hemocytes may also affect the antimicrobial activity of R. ferrugineus larvae, with an increase in phenoloxidase activity possibly correlated with microbial clearance and survival rates of larvae. The safety and toxicity of R. ferrugineus larvae extracts, as well as their long-term efficacy, are also addressed in this paper. The implications of future research are explored in this paper, and it is certain that R. ferrugineus larvae have the potential to be developed as a broad-spectrum antimicrobial agent with proper investigation.