Discovery Of Antibacterial Compounds Research Articles

Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Mur ligase Family Members by In Silico Structure-Based Drug Screening.

Staphylococcus aureus (S. aureus) is a major bacterial infection in humans, leading to severe disease and causing death. The stagnation of antibiotic development in recent decades has made it difficult to combat drug-resistant infections. In this study, we performed an in silico structure-based drug screening (SBDS) targeting the S. aureus MurE (saMurE) enzyme involved in cell wall synthesis of S. aureus. saMurE is an enzyme that is essential for the survival of S. aureus but not present in humans. SBDS identified nine saMurE inhibitor candidates, Compounds 1-9, from a structural library of 154,118 compounds. Among them, Compound 2 showed strong antibacterial activity against Staphylococcus epidermidis (S. epidermidis) used as a model bacterium. Amino acid sequence homology between saMurE and S. epidermidis MurE is 87.4%, suggesting that Compound 2 has a similar inhibitory effect on S. aureus. Compound 2 showed an IC50 value of 301 nM for S. epidermidis in the dose-dependent growth inhibition assay. Molecular dynamics simulation showed that Compound 2 binds stably to both S. aureus MurD and S. aureus MurF, suggesting that it is a potential multi-pharmacological pharmacological inhibitor. The structural and bioactivity information of Compound 2, as well as its potential multiple-target activity, could contribute to developing new antimicrobial agents based on MurE inhibition.

Discovery of Antibacterial Compounds against Xanthomonas citri subsp. citri from a Marine Fungus Aspergillus terreus SCSIO 41202 and the Mode of Action.

Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a severe citrus disease. Currently, copper-containing pesticides are widely used to manage this disease, posing high risks to the environment and human health. This study reports the discovery of naturally occurring anti-Xcc compounds from a deep-sea fungus, Aspergillus terreus SCSIO 41202, and the possible mode of action. The ethyl acetate extract of A. terreus was subjected to bioassay-guided isolation, resulting in the discovery of eight anti-Xcc compounds (1-8) with minimum inhibitory concentrations (MICs) ranging from 0.078 to 0.625 mg/mL. The chemical structures of these eight metabolites were determined by integrative analysis of various spectroscopic data. Among these compounds, Asperporonin A (1) and Asperporonin B (2) were identified as novel compounds with a very unusual structural skeleton. The electronic circular dichroism was used to determine the absolute configurations of 1 and 2 through quantum chemical calculation. A bioconversion pathway involving pinacol rearrangement was proposed to produce the unusual compounds (1-2). Compound 6 exhibited an excellent anti-Xcc effect with a MIC value of 0.078 mg/mL, which was significantly more potent than the positive control CuSO4 (MIC = 0.3125 mg/mL). Compound 6 inhibited cell growth by disrupting biofilm formation, destroying the cell membrane, and inducing the accumulation of reactive oxygen species. In vivo tests indicated that compound 6 is highly effective in controlling citrus canker disease. These results indicate that compounds 1-8, especially 6, have the potential as lead compounds for the development of new, environmentally friendly, and efficient anti-Xcc pesticides.

Antibacterial Activity of Gonad Methanol Extract of the Sea Urchin Diadema Setosum Against Methicillin-Resistant Staphylococcus aureus and Escherichia coli

The discovery of antibacterial compounds from nature has been widely used as an effort to overcome the resistance of pathogenic bacteria. Sea urchin is a marine biota of phylum Echinoderms that has a potency as an antibacterial to the variety of pathogenic microbes. This study aims to determine the antibacterial activity of gonad extract on Diadema setosum against Methicillin-Resistant Staphylococcus Aureus bacteria and Escherichia coli bacteria. The Gonad of Diadema setosum was extracted by maseration and rotary evaporator. Phytochemical screening tests were performed on alkaloids, flavonoids, triterpenoids, steroids and phenolic compounds. The antibacterial activity test was performed by two different methods of agar diffusion method and microdilution broth method. The results of phytochemical screening tests showed that gonad methanol extract of the Diadema setosum contain flavonoid and saponin compounds. The result of the antibacterial activity test of the diffusion method showed that gonad methanol extract did not have antibacterial activity with no inhibition zone formed at all test concentrations. The result of antibacterial activity test of broth microdilution method showed that Minimum Inhibitory Concentration (MIC) value extract to MRSA and E. coli bacteria were 62,5 mg/ml, meanwhile Minimum Bactericidal Concentration (MBC) value was not found until even at the highest concentration.

The secondary metabolites of rare actinomycetes: chemistry and bioactivity.

Actinomycetes are outstanding and fascinating sources of potent bioactive compounds, particularly antibiotics. In recent years, rare actinomycetes have had an increasingly important position in the discovery of antibacterial compounds, especially Micromonospora, Actinomadura and Amycolatopsis. Focusing on the period from 2008 to 2018, we herein summarize the structures and bioactivities of secondary metabolites from rare actinomycetes, involving 21 genera.

Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase or ribosomal protein S12

We show that selection of drug-resistant bacterial mutants allows the discovery of antibacterial compounds. Mutant strains of a soil-isolated Streptomyces species that does not produce antibacterials synthesize a previously unknown class of antibacterial, which we name piperidamycin. Overall, 6% of non-Streptomyces actinomycetes species and 43% of Streptomyces species that do not produce antibacterials are activated to produce them. The antibacterial-producing mutants all carried mutations in RNA polymerase and/or the ribosomal protein S12.

A new β-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Helicobacter pylori: Molecular cloning, enzymatic characterization, and structural modeling

Helicobacter pylori is a gram-negative pathogenic bacterium that causes peptic ulcer disease and gastric cancer, and studies of the related potent enzymes associated with this bacterium are urgent for the discovery of novel drug targets. In bacteria, β-hydroxyacyl-acyl carrier protein (ACP) dehydratase (FabZ) is a potent enzyme in fatty acid biosynthesis and catalyzes the dehydration of β-hydroxyacyl-ACP to trans-2-acyl-ACP. In this study, the cloning and enzymatic characterization of FabZ from H. pylori strain SS1 (HpFabZ) were reported, and the gene sequence of Hp fabZ was deposited in the GenBank database (Accession No. AY725427). Enzyme dynamic analysis showed that HpFabZ had a K m of 82.6 ± 4.3 μM toward its substrate analog crotonoyl-CoA. Dynamic light scattering and native-PAGE investigations suggested that HpFabZ exists as hexamer in native state. Enzymatic characterization and thermal-induced unfolding analysis based on circular dichroism spectral measurements indicated that HpFabZ is very stable against high temperature (90 °C). Such a high stability of HpFabZ was well elucidated by the strong H-bonds and hydrophobic interactions among the HpFabZ hexamer as investigated in the modeled HpFabZ hexamer structure. Our current study is hoped to provide useful information in better understanding the FabZ of H. pylori strain and further supply possible hints in the discovery of anti-bacterial compounds using HpFabZ as target.