Discovery Of Novel Antibacterial Agents Research Articles

Cladophora spp. Extracts Show Remarkable Antibacterial Potential Against Pseudomonas aeruginosa

Background: Bacterial resistance, influenced by genetic processes and adaptive strategies, necessitates the discovery of novel antibacterial agents, especially from natural sources. Specific Background: Pseudomonas aeruginosa, a notorious pathogen in urinary tract infections (UTIs), demonstrates considerable resistance to conventional therapies, necessitating alternative therapeutic approaches. Knowledge Gap: Research indicates that while natural sources like Cladophora spp. offer antibacterial agents, their effectiveness in combating P. aeruginosa resistant strains remains underexplored. Aims: This study aims to evaluate the antibacterial potential of Cladophora spp. algae extracts against Pseudomonas aeruginosa isolated from UTIs, utilizing solvent extraction, MIC determination, disc diffusion assays, and GC-MS analysis to identify bioactive compounds. Results: All extracts, including those prepared with water, ethanol, and hexane, demonstrated inhibitory effects on P. aeruginosa. The hexane extract exhibited the most significant activity, with a mean zone of inhibition of 13.0 ± 0.7 mm at a concentration of 50%. GC-MS analysis identified several bioactive compounds potentially responsible for these effects. Novelty: This study is among the first to investigate Cladophora spp. as a source of antibacterial agents specifically targeting P. aeruginosa, providing new insights into the potential of algae-based therapeutics. Implications: Cladophora spp. holds promise as a source of novel antibacterial compounds, with potential for multidrug-resistant infections treatments. Further research is needed for clinical application. Highlights: Hexane Extract: Most effective against Pseudomonas aeruginosa. Novel Source: Cladophora spp. shows potential as antibacterial agent. GC-MS Findings: Identified key bioactive compounds. Keywords: Cladophora spp., Pseudomonas aeruginosa, antibacterial agents, natural extracts, GC-MS analysis

Synthesis, Characterization, Molecular Docking, and Molecular Dynamics Studies of Schiff Bases of 2-Phenoxy-1-Phenyl-Ethanone as Antibacterial Agents

Background: The development of antimicrobial resistance and reduced discovery and commercialization of newer antibiotics point to the need for the discovery of novel anti-bacterial agents. Schiff bases are reported to possess a broad range of pharmacological activi-ties, which also include antibacterial activity. With this background, novel Schiff bases were synthesized. Aim: The present study aimed to synthesize novel Schiff bases of 2-phenoxy-1-phenyl-etha-none with aryl amines and evaluate their antibacterial activity. Methods: The desired Schiff bases were synthesized by condensing various aryl amines with 2-bromo-1-phenylethanone and characterized by physicochemical and spectral methods. The antibacterial activity of the synthesized Schiff bases was determined by the cup diffusion method. Molecular docking with Staphylococcus aureus tyrosyl-t-RNA synthetase (Protein Data Bank ID: 1JIJ) was performed using Autodock. Molecular dynamics simulation studies were performed using GROMACS. ADME analysis and drug-likeliness of the synthesized compounds were predicted using SwissADME. Protein-ligand interactions were studied using BIOVIA Discovery Studio Visualizer. Results: Out of the synthesized compounds, two compounds, sb_04 and sb_05, exhibited fair antibacterial activity. The compounds sb_04 and sb_05 exhibited better binding energy values than the original ligand of the target enzyme and comparable binding energy with ampicillin. The Autodock program estimated the binding free energy and inhibition constant values of compound sb_05 as -9.18 kcal/mol and 187.33 nM and for the compound sb_04 as -8.82 kcal/mol and 341.59 nM, respectively. The RMSD values of the compound sb_04 were stable throughout the duration of the simulation; however, the compound sb_05 showed lesser sta-bility in the docked complex. Interestingly, the compound sb_05 (-182.754 kJ/mol) exhibited stable interaction with a lower value of total interaction energy than sb_04 (-136.304 kJ/mol). The synthesized Schiff bases showed no violation of Lipinski’s rule of five and a bioavailabil-ity score in the range of 55% to 85%. Conclusion: The synthesized Schiff bases present a scaffold for the development of novel antibacterial agents, in particular the compounds sb_04 and sb_05.

Sub-lethal concentration of a colloidal nanosilver formulation (Silversol®) triggers dysregulation of iron homeostasis and nitrogen metabolism in multidrug resistant Pseudomonas aeruginosa

BackgroundPseudomonas aeruginosa is a notorious pathogen. Its multidrug resistant strains are listed among priority pathogens against whom discovery of novel antibacterial agents and, elucidation of new anti-pathogenicity mechanisms are urgently warranted. This study describes multiple antibacterial effects of a colloidal nano-silver formulation- Silversol® against a multi-drug resistant strain of P. aeruginosa.ResultsMinimum inhibitory concentration (MIC) of Silversol® against P. aeruginosa was found to be 1.5 ppm; and at sub-MIC of 1 ppm, it was able to alter quorum-sensing regulated pigmentation (pyocanin 82%↓; pyoverdine 48%↑), exopolysaccharide synthesis (76%↑) and biofilm formation, susceptibility to antibiotics (streptomycin and augmentin), protein synthesis and export (65%↑), nitrogen metabolism (37%↑ nitrite accumulation), and siderophore production in this pathogen. Network analysis of the differentially expressed genes in the transcriptome of the silversol-treated bacterium identified ten genes as the potential molecular targets: norB, norD, nirS, nirF, nirM, nirQ, nosZ, nosY, narK1, and norE (all associated with nitrogen metabolism or denitrification). Three of them (norB, narK1, and norE) were also validated through RT-PCR.ConclusionsGeneration of nitrosative stress and disturbance of iron homeostasis were found to be the major mechanisms associated with anti-Pseudomonas activity of Silversol®.

Thin Layer Chromatography Bio-autography guided identification of Antibacterial constituents of leaf extract of Stereospermum kunthianum Cham. (Bignoniaceae)

Background: There is an incessant quest for the discovery of novel antibacterial agents. Stereospermum kunthianum Cham.  Bignoniaceae) is used in traditional medicine in Nigeria and other parts of Africa in the treatment of venereal diseases e.g., syphilis,  wounds, refractory cough, malaria, tooth ache leprosy etc. The present work investigates the antimicrobial activity and phytochemical constituents of the ethanolic leaf extract of the plant.  Methods: Ethanolic leaf extract of S.Kunthianum was obtained by macerations method. Agar well diffffusion method was used to carry  out preliminary antimicrobial susceptibility testing. The test was carried out at extract concentration of 100, 200 and 400 mgmL-1 . The  agar dilution method was used to determine the Minimum Inhibitory Concentration (MIC) of the extracts. Phytochemical screening  was conducted using standard procedures. Thin layer chromatography bioautography analysis was carried out using the agar overlay  method. Six micro-organisms including two gram positive- Bacillus subtilis and Staphylococcus aureus, two gram negative Salmonella  typhi , and Pseudomonas aeruginosa, two fungi, Aspergillus niger and Candida albicans were used as test organisms.  Results: The ethanol extracts of S.kunthianum leaves showed antimicrobial activity against B.subtilis, S.aureus and S.typhi with zones of  Inhibition ranging from 13±1.41 to 29.5 ± 1.00 mm and MIC values ranging from 16 -64 mgmL-1 . Phytochemical screening revealed the  presence of saponins, flflavonoids and terpenoid compounds  Conclusion: The study showed that the antibacterial activities of the leaf extract are probably due to polyphenolic and steroidal  compounds.  &nbsp

Phage Display-Derived Peptides and Antibodies for Bacterial Infectious Diseases Therapy and Diagnosis

The emergence of antibiotic-resistant-bacteria is a serious public health threat, which prompts us to speed up the discovery of novel antibacterial agents. Phage display technology has great potential to screen peptides or antibodies with high binding capacities for a wide range of targets. This property is significant in the rapid search for new antibacterial agents for the control of bacterial resistance. In this paper, we not only summarized the recent progress of phage display for the discovery of novel therapeutic agents, identification of action sites of bacterial target proteins, and rapid detection of different pathogens, but also discussed several problems of this technology that must be solved. Breakthrough in these problems may further promote the development and application of phage display technology in the biomedical field in the future.

Evaluation of potential bacterial protease inhibitor properties of selected hydroxyquinoline derivatives: an in silico docking and molecular dynamics simulation approach

Antimicrobial drug resistance (AMR) is a severe global threat to public health. The increasing emergence of drug-resistant bacteria requires the discovery of novel antibacterial agents. Quinoline derivatives have previously been reported to exhibit antimalarial, antiviral, antitumor, antiulcer, antioxidant and, most interestingly, antibacterial properties. In this study, we evaluated the binding affinity of three newly designed hydroxyquinolines derived from sulfanilamide (1), 4-amino benzoic acid (2) and sulfanilic acid (3) towards five bacterial protein targets (PDB ID: 1JIJ, 3VOB, 1ZI0, 6F86, 4CJN). The three derivatives were designed considering the amino acid residues identified at the active site of each protein involved in the binding of each co-crystallized ligand and drug-likeness properties. The ligands displayed binding energy values with the target proteins ranging from −2.17 to −8.45 kcal/mol. Compounds (1) and (3) showed the best binding scores towards 1ZI0/3VOB and 1JIJ/4CJN, respectively, which may serve as new antibiotic scaffolds. Our in silico results suggest that sulfanilamide (1) or sulfanilic acid (3) hydroxyquinoline derivatives have the potential to be developed as bacterial inhibitors, particularly MRSA inhibitors. But before that, it must go through the proper preclinical and clinical trials for further scientific validation. Further experimental studies are warranted to explore the antibacterial potential of these compounds through preclinical and clinical studies. Communicated by Ramaswamy H. Sarma

Comparison of anti-bacterial activity of the leaves extract of moringa olifera and murraya koenigii

The present study was to performed to compare the the antibaterial activity of crude extract of leaves of moringa oliefera and murraya koenigii against staphylococcus aureus by using agar steak plate method ,hydroalcoholic solvent is used during the study .moringa oliefera showed effective aantibacterial activity than murraya koenigii.priliminary phytochemical investigation on crude extracts of leaves of moringa and murraya are performed, it showed alkaloids,tannins, glycocides, flavonoids and aminoacids presence of these secondary metabolites indicates the pharmacological activity of plant leaves . on the basis of this finding, the extracts demonstrating antibacterial activity could results in discovery of novel anti-bacterial agents. KEYWORDS: Moringaoliefera, murraya koenigii, hydroalcholic, flavonoids, antibacterial activity

Investigating the antimicrobial activity of a crude leaf extract derived from Piper species.

A growing number of human pathogens are becoming resistant to most common antibiotics. Each year, antibiotic-resistant infections are responsible for 35,000 deaths in the United States and billions of dollars in health care costs. This problem is magnified by the fact that very few new antibiotic therapies have been developed and approved for human use in recent years. Historically, plants and other products found in nature have served as essential sources for the discovery of novel antibacterial agents. Piper species are aromatic plants whose secondary metabolites have been shown to have wide ranging human health effects including anti-tumor, anti-diabetic, and anti-inflammatory activity. In collaboration with Dr. Claudia Ospina at Inter American University of Puerto Rico, we generated a crude chemical extract from Piper leaves and will be assessing the antimicrobial activity of this extract against a broad range of bacterial species known to exhibit multidrug resistance. Future studies will involve isolating the active compounds (and/or fractions) from the Piper crude extract using column chromatography and/or HPLC. The pure compounds will be characterized using different spectroscopic techniques such as NMR, IR and MS. We anticipate isolating and identifying several bioactive compounds from the crude Piper leaf extract that exhibit antimicrobial activity.

Screening for Antibacterial Activity of Chemical Extracts from Puerto Rican Plants.

Antibiotic resistance is one of the world’s most urgent public health threats. According to the Centers for Disease Control and Prevention, at least 2.8 million people get an antibiotic-resistant infection each year, and more than 35,000 people die in the United States from these infections. The development of new antibiotics is essential to combat this crisis and prevent the loss of additional lives. Natural products have historically been an essential source for the discovery of novel antibacterial agents. Furthermore, several studies have shown Puerto Rican plant extracts possess biologically active compounds. Therefore, we sought to determine whether extracts derived from Puerto Rican plants have broad-spectrum antimicrobial activity against a variety of pathogenic bacteria. Using a broth microdilution assay, we screened thirteen extracts generated from different plant species for antibacterial activity. Each extract was tested against the ESKAPE pathogens, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp, which are known to exhibit multidrug resistance. All extracts tested thus far were ineffective at inhibiting bacterial growth with the exception of the Bucida buceras leaf extract which showed broad spectrum antibacterial activity against E. faecalis, K. pneumoniae, and E. aerogenes. We are currently validating the antimicrobial activity of B. buceras extract through other antibiotic susceptibility assays. Here, we have shown that Puerto Rican plants have potential as a source of novel antimicrobial agents.

Effect of Sudanese honey on bacteria strains

Eight types of Sudanese honey produced by Apis mellifera collected from Tabga region, River Nile State (North Central Sudan) of different floral sources, namely, Faseolus vulgaris " Fasoulia" , Balanites aegyptiaca" Hejleeg" , Acacia seyal var. seyal" Taleh Ahmr" , Faidherbia albida" Haraz" , Lawsonia inermis" Henna" , Tamarix nilotica" Tarfa" , Acacia seyal var. fistula" Taheh Abiyad" , and Acacia tortilis" Samur" were assayed for antibacterial activities against five clinical isolates bacteria associated with venereal diseases. These isolated bacteria include: Staphylococcus aureus, Escherichia coli, Klebsilla sp., Pseudomonas aeruginosa and Proteus sp. The antibacterial activity was determined by the method of Minimum Inhibitory Concentration (MIC). The study shows that the sensitivity of bacterial strains varies depending on the botanical source of the honey. The Minimum Inhibitory Concentration of honey ranged from <5 to >20 mg/ml." Fasoulia" ," Hejleeg" and" Taleh" honeys showed the highest activity against all tested bacteria. The antibacterial activity recorded for most honey samples used in the present study and the known safe use of honey without toxic effects suggest that honey could be used to treat venereal infections in a cheap and effective manner. Results of the present study also suggest a fairly good correlation between traditional therapeutic use and the in vitro antibacterial activity. These results corroborate the importance of ethnomedical surveys for screening honeys as a potential source of bioactive compounds. Hence these could result in discovery of novel antibacterial agents. Further bio-guided fractionation will be conducted for and to identify the active compounds.

Potential therapeutic targets from Mycobacterium abscessus (Mab): recently reported efforts towards the discovery of novel antibacterial agents to treat Mab infections.

Mycobacterium abscessus (Mab) are rapidly growing mycobacteria that cause severe and persistent infections in both skin and lung tissues. Treatment regimens involve the extended usage of complex combinations of drugs, often leading to severe adverse side effects, particularly in immunocompromised patients. Current macrolide therapies are gradually proving to be less effective, largely due to emergence of antibiotic resistance; there is therefore an increasing need for the discovery of new antibacterials that are active against Mab. This review highlights recent research centred upon a number of potential therapeutic targets from Mab (Ag85C, ClpC1, GyrB, MmpL3 and TrmD), and discusses the various approaches used to discover small molecule inhibitors, in the search for future antibiotics for the treatment of Mab infections.

Therapeutic Potential of Naturally Occurring Benzofuran Derivatives and Hybrids of Benzofurans with other Pharmacophores as Antibacterial Agents.

Gram-positive and Gram-negative pathogens are able to evade the host immune system, persist within the human host, and lead to severe disease and even death. At present, bacterial infections are one of the leading causes of morbidity and mortality across the world. The development of novel antibacterial agents still represents a challenging endeavor, which is mainly attributed to the continuous emergence of more virulent and drug-resistant pathogens. Benzofuran constitutes the core of diverse pharmacologically active compounds, and there are a variety of approved benzofuranbased drugs in the market or currently going through different clinical phases or registration statuses. Benzofurans could exert antibacterial activity through various mechanisms and possess pronounced activity; therefore, benzofuran is a useful skeleton for the discovery of novel antibacterial agents. This review focuses on the recent advancement of naturally occurring benzofuran derivatives and hybrids of benzofurans with other pharmacophores as antibacterial agents, covering articles published between January 2015 and July 2021. The chemical structures and structure-activity relationships are also discussed.

Antibacterial Activity Prediction Model of Traditional Chinese Medicine Based on Combined Data-Driven Approach and Machine Learning Algorithm: Constructed and Validated.

Traditional Chinese medicines (TCMs), as a unique natural medicine resource, were used to prevent and treat bacterial diseases in China with a long history. To provide a prediction model of screening antibacterial TCMs for the design and discovery of novel antibacterial agents, the literature about antibacterial TCMs in the China National Knowledge Infrastructure (CNKI) and Web of Science database was retrieved. The data were extracted and standardized. A total of 28,786 pieces of data from 904 antibacterial TCMs were collected. The data of plant medicine were the most numerous. The result of association rules mining showed a high correlation between antibacterial activity with cold nature, bitter and sour tastes, hemostatic, and purging fire efficacies. Moreover, TCMs with antibacterial activity showed a specific aggregation in the phylogenetic tree; 92% of them came from Tracheophyta, of which 74% were mainly concentrated in rosids, asterids, Liliopsida, and Ranunculales. The prediction models of anti-Escherichia coli and anti-Staphylococcus aureus activity, with AUC values (the area under the ROC curve) of 77.5 and 80.0%, respectively, were constructed by the Neural Networks (NN) algorithm after Bagged Classification and Regression Tree (Bagged CART) and Linear Discriminant Analysis (LDA) selection. The in vitro experimental results showed the prediction accuracy of these two models was 75 and 60%, respectively. Four TCMs (Cirsii Japonici Herba Carbonisata, Changii Radix, Swertiae Herba, Callicarpae Formosanae Folium) were proposed for the first time to show antibacterial activity against E. coli and/or S. aureus. The results implied that the prediction model of antibacterial activity of TCMs based on properties and families showed certain prediction ability, which was of great significance to the screening of antibacterial TCMs and can be used to discover novel antibacterial agents.

Synthesis, Characterization, And Evaluation Of The Antibacterial Activity Of Novel 5-aryl-2-amino 1,3,4 Thiadiazole Derivatives

The antibiotic resistant crisis is a worldwide phenomenon that threatens the global health. The misuse and overuse of antibiotics as well as the inadequate development of new antibacterial drugs have all drove the evolution of resistance. Thus, the development and discovery of novel antibacterial agents is a critical field within medicinal chemistry. In this study, a series of novel 1,3,4 thiadiazole derivatives containing imine group was synthesized. The chemical structures had been identified by 1H-NMR, FT-IR, Elemental Analysis (CHNS), and some physicochemical properties. The antibacterial activity of the synthesized compounds was evaluated against two gram-positive (Staphylococcus aureus, Enterococcus faecalis), and two gram negative (Escherichia coli, Klebsiella pneumonia) bacteria. Among the synthesized compounds, compounds e4, e5, and e6 were found to exhibit good antibacterial activity against the tested bacterial strains.

Discovery of novel antibacterial agents: Recent developments in D-alanyl-D-alanine ligase inhibitors.

Bacterial infections can cause serious problems that threaten public health over a long period of time. Moreover, the continuous emergence of drug-resistant bacteria necessitates the development of novel antibacterial agents. D-alanyl-D-alanine ligase (Ddl) is an indispensable adenosine triphosphate-dependent bacterial enzyme involved in the biosynthesis of peptidoglycan precursor, which catalyzes the ligation of two D-alanine molecules into one D-alanyl-D-alanine dipeptide. This dipeptide is an essential component of the intracellular peptidoglycan precursor, uridine diphospho-N-acetylmuramic acid (UDP-MurNAc)-pentapeptide, that maintains the integrity of the bacterial cell wall by cross-linking the peptidoglycan chain, and is crucial for the survival of pathogens. Consequently, Ddl is expected to be a promising target for the development of antibacterial agents. In this review, we present a brief introduction regarding the structure and function of Ddl, as well as an overview of the various Ddl inhibitors currently being used as antibacterial agents, specifically highlighting their inhibitory activities, structure-activity relationships and mechanisms of action.

Novel (+)-Neoisopulegol-Based O-Benzyl Derivatives as Antimicrobial Agents.

Discovery of novel antibacterial agents with new structures, which combat pathogens is an urgent task. In this study, a new library of (+)-neoisopulegol-based O-benzyl derivatives of aminodiols and aminotriols was designed and synthesized, and their antimicrobial activity against different bacterial and fungal strains were evaluated. The results showed that this new series of synthetic O-benzyl compounds exhibit potent antimicrobial activity. Di-O-benzyl derivatives showed high activity against Gram-positive bacteria and fungi, but moderate activity against Gram-negative bacteria. Therefore, these compounds may serve a good basis for antibacterial and antifungal drug discovery. Structure–activity relationships were also studied from the aspects of stereochemistry of the O-benzyl group on cyclohexane ring and the substituent effects on the ring system.

Effectiveness of Bioactive Compound as Antibacterial and Anti-Quorum Sensing Agent from Myrmecodia pendans: An In Silico Study.

Background: antibiotic resistance encourages the development of new therapies, or the discovery of novel antibacterial agents. Previous research revealed that Myrmecodia pendans (Sarang Semut) contain potential antibacterial agents. However, specific proteins inhibited by them have not yet been identified as either proteins targeted by antibiotics or proteins that have a role in the quorum-sensing system. This study aims to investigate and predict the action mode of antibacterial compounds with specific proteins by following the molecular docking approach. Methods: butein (1), biflavonoid (2), 3″-methoxyepicatechin-3-O-epicatechin (3), 2-dodecyl-4-hydroxylbenzaldehyde (4), 2-dodecyl-4-hydroxylbenzaldehyde (5), pomolic acid (6), betulin (7), and sitosterol-(6′-O-tridecanoil)-3-O-β-D-glucopyranoside (8) from M. pendans act as the ligand. Antibiotics or substrates in each protein were used as a positive control. To screen the bioactivity of compounds, ligands were analyzed by Prediction of Activity Spectra for Substances (PASS) program. They were docked with 12 proteins by AutoDock Vina in the PyRx 0.8 software application. Those proteins are penicillin-binding protein (PBP), MurB, Sortase A (SrtA), deoxyribonucleic acid (DNA) gyrase, ribonucleic acid (RNA) polymerase, ribosomal protein, Cytolysin M (ClyM), FsrB, gelatinase binding-activating pheromone (GBAP), and PgrX retrieved from UniProt. The docking results were analyzed by the ProteinsPlus and Discovery Studio software applications. Results: most compounds have Pa value over 0.5 against proteins in the cell wall. In nearly all proteins, biflavonoid (2) has the strongest binding affinity. However, compound 2 binds only three residues, so that 2 is the non-competitive inhibitor. Conclusion: compound 2 can be a lead compound for an antibacterial agent in each pathway.

How to Enter a Bacterium: Bacterial Porins and the Permeation of Antibiotics.

Despite tremendous successes in the field of antibiotic discovery seen in the previous century, infectious diseases have remained a leading cause of death. More specifically, pathogenic Gram-negative bacteria have become a global threat due to their extraordinary ability to acquire resistance against any clinically available antibiotic, thus urging for the discovery of novel antibacterial agents. One major challenge is to design new antibiotics molecules able to rapidly penetrate Gram-negative bacteria in order to achieve a lethal intracellular drug accumulation. Protein channels in the outer membrane are known to form an entry route for many antibiotics into bacterial cells. Up until today, there has been a lack of simple experimental techniques to measure the antibiotic uptake and the local concentration in subcellular compartments. Hence, rules for translocation directly into the various Gram-negative bacteria via the outer membrane or via channels have remained elusive, hindering the design of new or the improvement of existing antibiotics. In this review, we will discuss the recent progress, both experimentally as well as computationally, in understanding the structure-function relationship of outer-membrane channels of Gram-negative pathogens, mainly focusing on the transport of antibiotics.

1,2,4-Triazole hybrids with potential antibacterial activity against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has developed numerous mechanisms of virulence and strategies to evade the human immune system, and it can be transmitted between humans, animals, and the environment. Thus, MRSA is an important cause of morbidity and mortality in both hospitals and in the community, creating an urgent demand for the development of novel anti-MRSA candidates. The 1,2,4-triazole nucleus is a bioisostere of amide, ester, and carboxylic acid, and the 1,2,4-triazole ring is found in many compounds with diverse biological effects. 1,2,4-Triazole derivatives could exert their antibacterial activity through inhibition of efflux pumps, filamentous temperature-sensitive protein Z, penicillin-binding protein, DNA gyrase, and topoisomerase IV, and they play an important role in the discovery of novel antibacterial agents. Among them, 1,2,4-triazole hybrids, which have the potential to exert dual/multiple mechanisms of action, possess a promising broad-spectrum antibacterial activity against a panel of clinically important drug-resistant pathogens including MRSA. This review outlines the recent developments of 1,2,4-triazole hybrids with a potential anti-MRSA activity, covering articles published between 2010 and 2020. The mechanisms of action, critical aspects of their design, and structure-activity relationships are also discussed.

Protective Effect of Green Algae Ulva reticulata Against Pseudomonas aeruginosa in Drosophila Infection Model

The emergence of antibiotic-resistant Pseudomonas aeruginosa is one of main health issues in global communities. To overcome such threat, the discovery of novel antibacterial agents is indispensable. This study aimed to evaluate the in vivo antipseudomonal activity of Ulva reticulata extract in Drosophila model of infection. Ethanolic extract of Ulva reticulata was prepared using maceration method and the extract was subsequently assessed for its in vivo antibacterial effect against P. aeruginosa using survival assay, bacterial load enumeration, and gene expression analysis in the wildtype Drosophila. Survival and bacterial load analysis were further performed in a similar fashion on the mutant flies devoid of component responsible in the activation of immune responses against P. aeruginosa. Decline in the survival of infected host accompanied by augmentation of bacterial proliferation was documented in the wildtype Drosophila upon infection with P. aeruginosa. These phenotypic events were further amplified in immune-deficient mutant Drosophila. Nevertheless, improvement of host survivorship and reduction of bacterial burden were demonstrated in both wildtype or immune-deficient mutant flies upon treatment with Ulva reticulata extract after bacterial challenge. Our data demonstrated in vivo antipseudomonal activity of Ulva reticulata extract and thus provide a valuable information about its future potential for health promotion.