scholarly journals De novo design of a pH-triggered self-assembled β-hairpin nanopeptide with the dual biological functions for antibacterial and entrapment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiuke Li ◽  
Jinze Li ◽  
Weikang Yu ◽  
Zhihua Wang ◽  
Jiawei Li ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
De Novo ◽  
Ph Regulation ◽  
Membrane Integrity ◽  
Intestinal Flora ◽  
Building Blocks ◽  
Self Assembled

Abstract Background Acid-tolerant enteric pathogens can evade small intestinal acid barriers, colonize and infect the intestinal tract. However, broad-spectrum antibiotics are not the best therapeutic strategy because of the disruption of intestinal flora caused by its indiscriminate antimicrobial activity against beneficial and harmful bacteria. So that is what inspired us to combine pH regulation with nanotechnology to develop a pH-triggered site-targeted antimicrobial peptide with entrapping function. Results A pH-triggered dual biological functional self-assembled peptide (SAP) was designed according to the features of amino-acid building blocks and the diagonal cation–π interaction principle. The results of characterization experiments showed that changes in pH conditions could trigger microstructural transformation of the nanopeptide from nanospheres to nanofibers. The subsequent antibacterial and toxicity experiments determined that SAP had great antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Bacillus cereus above 15.6 μg/mL under acidic conditions by disrupting bacterial membrane integrity, excellent biocompatibility in vitro even at 250 μg/mL and high tolerance in physical environment. Moreover, at peptide concentrations greater than 62.5 μg/mL, SAP showed the entrapment property, which played an important role in phagocytic clearance in infection forces. Meanwhile, the in vivo results revealed that SAP possessed excellent therapeutic effect and good biosafety. Conclusions Our study revealed the antibacterial activity of a short β-hairpin forming self-assembled peptide, and established an innovative design strategy for peptide-based nanomaterials and a new treatment strategy for gastrointestinal bacterial infections. Graphic Abstract

scholarly journals De Novo Design of a pH-triggered Self-assembled β-hairpin Nano Peptide for the Dual Biological Function of Antibacterial and Entrapment

2021 ◽  
Author(s):  
Qiuke Li ◽  
Jinze Li ◽  
Weikang Yu ◽  
Zhihua Wang ◽  
Jiawei Li ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
De Novo ◽  
Ph Regulation ◽  
Membrane Integrity ◽  
Intestinal Flora ◽  
Building Blocks ◽  
Self Assembled ◽  
High Concentrations

Abstract BackgroundAcid-tolerant enteric pathogens could evade small intestinal acid barriers, colonizing and infecting the intestinal tract. Whereas broad-spectrum antibiotics are not the best therapeutic strategy because of the disruption of intestinal flora caused by its indiscriminate antimicrobial activity against beneficial and harmful bacteria. So that is what inspired us to combine pH regulation with nanotechnology to develop a pH-triggered site-targeted antimicrobial peptide with entrapping function. ResultsAccording to the features of amino-acid building blocks and the diagonal cation–π interaction principle, a self-assembled peptide (SAP) was designed, and the results showed that changes in pH conditions could trigger the transformation of the microstructure of the nanopeptide, which has great antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Bacillus cereus under acidic conditions by disrupting bacterial membrane integrity, and great biocompatibility in vivo and in vitro and high tolerance. Moreover, SAP at high concentrations showed the entrapment property, which plays an important role in phagocytic clearance in the infection forces.ConclusionsOur study revealed the antibacterial activity of a short β-hairpin forming self-assembled peptide and establishes an innovative design strategy for peptide-based nanomaterials and a new treatment strategy for gastrointestinal bacterial infection.

scholarly journals De novo design of self-assembling helical protein filaments

Science ◽  
2018 ◽  
Vol 362 (6415) ◽  
pp. 705-709 ◽  
Author(s):  
Hao Shen ◽  
Jorge A. Fallas ◽  
Eric Lynch ◽  
William Sheffler ◽  
Bradley Parry ◽  
...  
Keyword(s):  
De Novo ◽  
Computational Design ◽  
Building Blocks ◽  
Repeat Units ◽  
Self Assembling ◽  
Wide Range ◽  
Helical Protein ◽  
Monomeric Proteins

We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this approach to design proteins that assemble into micrometer-scale filaments with a wide range of geometries in vivo and in vitro. Cryo–electron microscopy structures of six designs are close to the computational design models. The filament building blocks are idealized repeat proteins, and thus the diameter of the filaments can be systematically tuned by varying the number of repeat units. The assembly and disassembly of the filaments can be controlled by engineered anchor and capping units built from monomers lacking one of the interaction surfaces. The ability to generate dynamic, highly ordered structures that span micrometers from protein monomers opens up possibilities for the fabrication of new multiscale metamaterials.

scholarly journals Antimicrobial and Antihypercholesterolemic Activities of Pulicaria gnaphalodes

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090485 ◽  
Author(s):  
Syed Ali Raza Naqvi ◽  
Syed Muhammad Ali Shah ◽  
Laiba Kanwal ◽  
Muhammad Saeed ◽  
Atta-ul-Haq ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Methanol Extract ◽  
Ethanol Extract ◽  
Alternative Therapies ◽  
Zone Of Inhibition

Multidrug resistance has increased globally in the communities. Bacterial infections associated with health care have weakened the existing antimicrobial therapy and demand the search for alternative therapies. In the present investigation, the medicinal plant Pulicaria gnaphalodes from Quetta, Pakistan, has been screened for antimicrobial potential. In vitro antimicrobial efficacy of P gnaphalodes extracts (methanol and ethanol) was quantitatively evaluated on the basis of zone of inhibition against different bacteria and minimum inhibitory concentration (MIC). In vivo, antihypercholesterolemic activity is determined in different rat groups. The results of the study indicated that the ethanol extract of P gnaphalodes showed maximum zone of inhibition for Bacillus subtilis of 12.1 ± 1.1 mm from all others. The methanol extract showed maximum zone of inhibition for Staphylococcus aureus of 11.9 ± 1.0 mm and rifampicin showed maximum zone of inhibition of 23.1 ± 0.9 mm. The results of ethanol and methanol extract of P gnaphalodes against different bacteria revealed that this plant has greater antimicrobial activity. However, the plant extract shows nonsignificant antihypercholesterolemic activity. The extract of this plant can be utilized as medicine to inhibit several infections caused by some bacterial pathogens found in human body.

scholarly journals Evaluation of the Antimicrobial Activity of Lysostaphin-Coated Hernia Repair Meshes

2011 ◽  
Vol 55 (9) ◽  
pp. 4379-4385 ◽  
Author(s):  
Rohan Satishkumar ◽  
Sriram Sankar ◽  
Yuliya Yurko ◽  
Amy Lincourt ◽  
John Shipp ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Hernia Repair ◽  
Bacterial Infections ◽  
Synthetic Mesh ◽  
Content Type ◽  
Wound Fluid ◽  
Count Model ◽  
Mesh Surface

ABSTRACTBacterial infections by antibiotic-resistantStaphylococcus aureusstrains are among the most common postoperative complications in surgical hernia repair with synthetic mesh. Surface coating of medical devices/implants using antibacterial peptides and enzymes has recently emerged as a potentially effective method for preventing infections. The objective of this study was to evaluate thein vitroantimicrobial activity of hernia repair meshes coated by the antimicrobial enzyme lysostaphin at different initial concentrations. Lysostaphin was adsorbed on pieces of polypropylene (Ultrapro) mesh with binding yields of ∼10 to 40% at different coating concentrations of between 10 and 500 μg/ml. Leaching of enzyme from the surface of all the samples was studied in 2% (wt/vol) bovine serum albumin in phosphate-buffered saline buffer at 37°C, and it was found that less than 3% of adsorbed enzyme desorbed from the surface after 24 h of incubation. Studies of antibacterial activity against a cell suspension ofS. aureuswere performed using turbidity assay and demonstrated that the small amount of enzyme leaching from the mesh surface contributes to the lytic activity of the lysostaphin-coated samples. Colony counting data from the broth count (model for bacteria in wound fluid) and wash count (model for colonized bacteria) for the enzyme-coated samples showed significantly decreased numbers of CFU compared to uncoated samples (P< 0.05). A pilotin vivostudy showed a dose-dependent efficacy of lysostaphin-coated meshes in a rat model ofS. aureusinfection. The antimicrobial activity of the lysostaphin-coated meshes suggests that such enzyme-leaching surfaces could be efficient at actively resisting initial bacterial adhesion and preventing subsequent colonization of hernia repair meshes.

scholarly journals Antimicrobial Activity Study of Chinese Medicine Madeng’ai

2021 ◽  
Author(s):  
Zhenrong Tang ◽  
Yannan Zhao ◽  
Zaiqi Zhang ◽  
Huan Yue ◽  
Dan Wang ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Chinese Medicine ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Control Treatment ◽  
Resistant Bacteria ◽  
Mice Model ◽  
Bacteria Growth

Abstract Background Due to the overuse of antibiotics, many multidrug-resistant bacteria have emerged, which brings huge challenges to the clinical treatment of bacterial infections. New products for anti-infection are necessary. Methods Madeng’ai powder was added with Milli-Q water or LB culture and autoclaved to prepare medicine suspension at different concentration. Bacteria were cultured in LB with different concentration of Madeng’ai. and swab on LB agar plates to get minimal inhibitory concentration (MIC) of Madeng’ai. Mice back was cut to make wound and MRSA/PAE suspension was injected in the wound area. Then swab with Madeng’ai extracts. Bacteria growth of infected secretions was checked on LB agar, and Hematoxylin and eosin (H&E) staining was performed for Histological analysis of skin tissues infected with bacteria after Madeng’ai and PBS (control) treatment. Results Madeng’ai could widely inhibit E.faecalis, Pseudomonas aeruginosa (PAE), Klebsiella pneumoniae (K.pneumoniae) and Acinetobacter baumannii (A.baumannii) at concentration of 4.0 mg/ml. The mice model also showed that Madeng’ai had imposed restrictions on MRSA and PAE growth in vivo. Conclusion Here, we report that a new Chinese medicine Madeng’ai has antimicrobial activity functions in vitro and in vivo. These data briefly showed that Madeng’ai functioned on antimicrobial and provided a new consideration for an antibiosis product.

scholarly journals Recent Advances in Iron Chelation and Gallium-Based Therapies for Antibiotic Resistant Bacterial Infections

2021 ◽  
Vol 22 (6) ◽  
pp. 2876
Author(s):  
Víctor Vinuesa ◽  
Michael J. McConnell
Keyword(s):  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Iron Chelation ◽  
Iron Chelator ◽  
In Vivo Studies ◽  
Iron Chelators

Iron is essential for multiple bacterial processes and is thus required for host colonization and infection. The antimicrobial activity of multiple iron chelators and gallium-based therapies against different bacterial species has been characterized in preclinical studies. In this review, we provide a synthesis of studies characterizing the antimicrobial activity of the major classes of iron chelators (hydroxamates, aminocarboxylates and hydroxypyridinones) and gallium compounds. Special emphasis is placed on recent in-vitro and in-vivo studies with the novel iron chelator DIBI. Limitations associated with iron chelation and gallium-based therapies are presented, with emphasis on limitations of preclinical models, lack of understanding regarding mechanisms of action, and potential host toxicity. Collectively, these studies demonstrate potential for iron chelators and gallium to be used as antimicrobial agents, particularly in combination with existing antibiotics. Additional studies are needed in order to characterize the activity of these compounds under physiologic conditions and address potential limitations associated with their clinical use as antimicrobial agents.

Synthesis of Novel 3(N,N-dialkylamino)alkyl/phenyl Substituted Thieno [2,3-d]pyrimidinones as H1-Anti-Histaminic and Antimicrobial Agents

2019 ◽  
Vol 15 (1) ◽  
pp. 63-70
Author(s):  
Shiv Dev Singh ◽  
Arvind Kumar ◽  
Firoz Babar ◽  
Neetu Sachan ◽  
Arun Kumar Sharma
Keyword(s):  
Antimicrobial Activity ◽  
Potassium Hydroxide ◽  
Antimicrobial Agents ◽  
Pyrimidine Ring ◽  
Antimicrobial Activities ◽  
Screening Methods ◽  
Chlorpheniramine Maleate ◽  
In Vivo Screening

Background: Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine. Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity. Objective: Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones as H1-anti-histaminic and antimicrobial agents. Methods: A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b) thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]- 2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and antimicrobial activities. Results: All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.

Kinase Targets for Mycolic Acid Biosynthesis in Mycobacterium tuberculosis

2019 ◽  
Vol 12 (1) ◽  
pp. 27-49 ◽  
Author(s):  
Shahinda S.R. Alsayed ◽  
Chau C. Beh ◽  
Neil R. Foster ◽  
Alan D. Payne ◽  
Yu Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Enzymatic Activity ◽  
Bacterial Pathogen ◽  
Building Blocks ◽  
Mycolic Acid ◽  
Adaptive Responses ◽  
Mycolic Acids ◽  
Hydroxylated Fatty Acids

Background:Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercle bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic machineries involved in the biosynthesis of MAs in M.tb. However, gaps still remain in the exact role of the phosphorylation and dephosphorylation of regulatory mechanisms within these systems. To date, a total of 11 serine-threonine protein kinases (STPKs) are found in M.tb. Most enzymes implicated in the MAs synthesis were found to be phosphorylated in vitro and/or in vivo. For instance, phosphorylation of KasA, KasB, mtFabH, InhA, MabA, and FadD32 downregulated their enzymatic activity, while phosphorylation of VirS increased its enzymatic activity. These observations suggest that the kinases and phosphatases system could play a role in M.tb adaptive responses and survival mechanisms in the human host. As the mycobacterial STPKs do not share a high sequence homology to the human’s, there have been some early drug discovery efforts towards developing potent and selective inhibitors.Objective:Recent updates to the kinases and phosphatases involved in the regulation of MAs biosynthesis will be presented in this mini-review, including their known small molecule inhibitors.Conclusion:Mycobacterial kinases and phosphatases involved in the MAs regulation may serve as a useful avenue for antitubercular therapy.

scholarly journals High-throughput screening and rational design of biofunctionalized surfaces with optimized biocompatibility and antimicrobial activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhou Fang ◽  
Junjian Chen ◽  
Ye Zhu ◽  
Guansong Hu ◽  
Haoqian Xin ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
High Throughput ◽  
High Throughput Screening ◽  
Rational Design ◽  
Click Reaction ◽  
Reaction Times ◽  
Great Promise ◽  
Biomaterial Surfaces

AbstractPeptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.

scholarly journals Novel Derivatives of 4-Methyl-1,2,3-Thiadiazole-5-Carboxylic Acid Hydrazide: Synthesis, Lipophilicity, and In Vitro Antimicrobial Activity Screening

2021 ◽  
Vol 11 (3) ◽  
pp. 1180
Author(s):  
Kinga Paruch ◽  
Łukasz Popiołek ◽  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Malm ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Carboxylic Acid ◽  
Bacterial Infections ◽  
Acid Hydrazide ◽  
Antimicrobial Effect ◽  
In Vitro Antimicrobial Activity ◽  
Research Goal ◽  
New Compounds ◽  
Derivatives Of

Bacterial infections, especially those caused by strains resistant to commonly used antibiotics and chemotherapeutics, are still a current threat to public health. Therefore, the search for new molecules with potential antimicrobial activity is an important research goal. In this article, we present the synthesis and evaluation of the in vitro antimicrobial activity of a series of 15 new derivatives of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid. The potential antimicrobial effect of the new compounds was observed mainly against Gram-positive bacteria. Compound 15, with the 5-nitro-2-furoyl moiety, showed the highest bioactivity: minimum inhibitory concentration (MIC) = 1.95–15.62 µg/mL and minimum bactericidal concentration (MBC)/MIC = 1–4 µg/mL.

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