Discovery of a novel antibacterial protein CB6-C to target methicillin-resistant Staphylococcus aureus

Given a serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with methicillin-resistant Staphylococcus aureus as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, Sephadex G-75 column, QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31.405 kDa by SDS-PAGE. LC–MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% identity with chitosanase (Csn) produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 μg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in in vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.

Engineered Bacteriophage as a Delivery Vehicle for Antibacterial Protein, SASP

The difficulties in developing novel classes of antibacterials is leading to a resurgence of interest in bacteriophages as therapeutic agents, and in particular engineered phages that can be optimally designed. Here, pre-clinical microbiology assessment is presented of a Staphylococcus aureus phage engineered to deliver a gene encoding an antibacterial small acid soluble spore protein (SASP) and further, rendered non-lytic to give product SASPject PT1.2. PT1.2 has been developed initially for nasal decolonisation of S. aureus, including methicillin-resistant S. aureus. Time-kill curve assays were conducted with PT1.2 against a range of staphylococcal species, and serial passaging experiments were conducted to investigate the potential for resistance to develop. SASPject PT1.2 demonstrates activity against 100% of 225 geographically diverse S. aureus isolates, exquisite specificity for S. aureus, and a rapid speed of kill. The kinetics of S. aureus/PT1.2 interaction is examined together with demonstrating that PT1.2 activity is unaffected by the presence of human serum albumin. SASPject PT1.2 shows a low propensity for resistance to develop with no consistent shift in sensitivity in S. aureus cells passaged for up to 42 days. SASPject PT1.2 shows promise as a novel first-in-class antibacterial agent and demonstrates potential for the SASPject platform.

A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria

The human intestine harbors a highly complex microbial community; interpersonal variation in this community can impact pathogen susceptibility, metabolism, and other aspects of health. Here, we identified and characterized a commensal-targeting antibacterial protein encoded in the gut microbiome.

Discovery of a Novel Antibacterial Protein CB6-C to Target Methicillin-Resistant Staphylococcus Aureus

Given the serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with MRSA as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, a Sephadex G-75 column, a QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31405.48 Da by SDS-PAGE. LC-MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% homology with chitosanase Csn produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 μg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in In Vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.

In- vitro Pharmacological investigation and Molecular Docking validation of Rhodiola rosea root against Bacterial and Helminthiasis infections

The present study's objective was to identify the phytoconstituents present in methanolic extract of Rhodiola rosea (R. rosea) with a help of Gas chromatography-Mass Spectrometry (GC-MS). The extract was subjected for the antibacterial (Escherichia coli ) and anthelmintic (adult Indian earthworms-Pheretima posthuma)in-vitro activities followed by the validation of the same by subjecting the bioactive compounds obtained in GCMS analysis to molecular docking studies for anthelmintic and antibacterial protein targets. Six compounds with molecular formula C12H14O4NF3, C9H14O2Si, C29H44O12, C18H30O, C12H23O2N, and C17H32O were identified in GCMS analysis. Different extract concentrations viz 50, 75, 100, 150, and 200 mg/ml and 50, 75, 100, 150, and 200 µg/ml for anthelmintic activity and anti-bacterial activity respectively. For anthelmintic protein target, results of molecular docking (presented by 3D & 2D model) revealed that the identified compounds (binding energy -6.05 to -8.40 Kcal/mol) exhibited a comparable binding affinity as that of albendazole(binding energy -9.54 Kcal/mol) except C3 (binding energy +33.42 Kcal/mol) compound. antibacterial protein target, compounds' binding affinities were found to be in the range -4.49 to -6.68 Kcal/mol, while chlorobiocin was found to be -4.75 Kcal/mol. The extract exhibited dose-dependent in-vitroanthelmintic (150 and 200 mg/ml) and antibacterial activity (150 and 200 µg/ml. The minimum lethal amount of extract concentration for anthelmintic activity was found to be 150 μg/ml. At this concentration, Pheretimaposthuma died in 33.56 ± 2.15 min while with a standard dose of albendazole, the lethal time was found to be 22.75 ± 1.63 min. Finally concluded that the identified bioactive compounds from R. rosea have the potential anthelmintic and antibacterial activity as justified by in-vitro biological evaluations and molecular docking studies.

Nutritional Assessment and Biological Activity of Moringa oleifera

Moringa oleifera medicinal plant is used for medicinal purposes for the treatment of different types of human diseases. The fresh roots, stems, leaves, flowers and seeds have been selected for such medicinal purposes. The findings of present study indicated that an appreciable amount of proximate composition and phytochemical had been confirmed. The leaves and seeds for this study showed significant phytochemical sources including phenolic compound, flavonoid, tannin alkaloid and antioxidant content, whereas the most sensitive minerals composition sources including Ca, Fe, Mg, Na, K, antibacterial activity including the Escherichia coli, Bacillus cereus and Staphylococcus aurous were found to be the most sensitive, while Klebsiella pneumonia least sensitive in this study. The growth of Escherichia coli is mostly inhibited by all plants components. Whereas, flowers and leaves showed good inhibition zone against Escherichia coli. The flowers of Maringa oleifera possessed antibacterial protein and peptide which showed highly significant against Staphylococcus aurous, Escherichia coli, Klebsiella pneumonia, Pseudomonas, proteus and enterobacter. The research will be supported for nutrition and sources of new drugs for the treatment of the different types of diseases.

A comprehensive overview of the synthesis of Tetrahydrocarbazoles and its biological properties

: Tetrahydrocarbazoles (THC) is a privileged structural scaffold containing natural indole as the central moiety. This extraordinary skeleton features in a plethora of naturally occurring pharmacological compounds and alkaloids exhibiting a significant inhibitory activity such as antibacterial, protein kinase inhibitor, and tumor growth inhibitor, etc. Due to its versatile biological properties, it always gains considerable attention among the scientific community. The main objective of this review is to make a comprehensive reference work on the synthesis and biological properties of THCs, thus targeting a broad audience on the assessment of various catalysts along with their reaction condition, mechanism of action, and yield, which are categorized into three groups: 1) organocatalyzed reactions; 2) TfOH catalyzed reactions; 3) metal-catalyzed reactions and 4) miscellaneous.