scholarly journals Antimicrobial Peptide Modifications against Clinically Isolated Antibiotic-Resistant Salmonella

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4654
Author(s):  
Suthee Mangmee ◽  
Onrapak Reamtong ◽  
Thareerat Kalambaheti ◽  
Sittiruk Roytrakul ◽  
Piengchan Sonthayanon
Keyword(s):  
Antibacterial Activity ◽  
Hemolytic Activity ◽  
Multidrug Resistant ◽  
Terminal Group ◽  
Scorpion Venom ◽  
Antibiofilm Activity ◽  
Peptide Antibiotic ◽  
Dependent Manner ◽  
C Terminus ◽  
Relationship Of

Antimicrobial peptides are promising molecules to address the global antibiotic resistance problem, however, optimization to achieve favorable potency and safety is required. Here, a peptide-template modification approach was employed to design physicochemical variants based on net charge, hydrophobicity, enantiomer, and terminal group. All variants of the scorpion venom peptide BmKn-2 with amphipathic α-helical cationic structure exhibited an increased antibacterial potency when evaluated against multidrug-resistant Salmonella isolates at a MIC range of 4–8 µM. They revealed antibiofilm activity in a dose-dependent manner. Sheep red blood cells were used to evaluate hemolytic and cell selectivity properties. Peptide Kn2-5R-NH2, dKn2-5R-NH2, and 2F-Kn2-5R-NH2 (variants with +6 charges carrying amidated C-terminus) showed stronger antibacterial activity than Kn2-5R (a variant with +5 charges bearing free-carboxyl group at C-terminus). Peptide dKn2-5R-NH2 (d-enantiomer) exhibited slightly weaker antibacterial activity with much less hemolytic activity (higher hemolytic concentration 50) than Kn2-5R-NH2 (l-enantiomer). Furthermore, peptide Kn2-5R with the least hydrophobicity had the lowest hemolytic activity and showed the highest specificity to Salmonella (the highest selectivity index). This study also explained the relationship of peptide physicochemical properties and bioactivities that would fulfill and accelerate progress in peptide antibiotic research and development.

scholarly journals Production of a New Thiopeptide Antibiotic, TP-1161, by a Marine Nocardiopsis Species

2010 ◽  
Vol 76 (15) ◽  
pp. 4969-4976 ◽  
Author(s):  
Kerstin Engelhardt ◽  
Kristin F. Degnes ◽  
Michael Kemmler ◽  
Harald Bredholt ◽  
Espen Fj�rvik ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Molecular Taxonomy ◽  
Multidrug Resistant ◽  
Peptide Antibiotic ◽  
Indicator Organisms ◽  
Bacterial Strains ◽  
Pcr Screening ◽  
Vancomycin Resistant ◽  
Antibacterial And Antifungal

ABSTRACT Twenty-seven marine sediment- and sponge-derived actinomycetes with a preference for or dependence on seawater for growth were classified at the genus level using molecular taxonomy. Their potential to produce bioactive secondary metabolites was analyzed by PCR screening for genes involved in polyketide and nonribosomal peptide antibiotic synthesis. Using microwell cultures, conditions for the production of antibacterial and antifungal compounds were identified for 15 of the 27 isolates subjected to this screening. Nine of the 15 active extracts were also active against multiresistant Gram-positive bacterial and/or fungal indicator organisms, including vancomycin-resistant Enterococcus faecium and multidrug-resistant Candida albicans. Activity-guided fractionation of fermentation extracts of isolate TFS65-07, showing strong antibacterial activity and classified as a Nocardiopsis species, allowed the identification and purification of the active compound. Structure elucidation revealed this compound to be a new thiopeptide antibiotic with a rare aminoacetone moiety. The in vitro antibacterial activity of this thiopeptide, designated TP-1161, against a panel of bacterial strains was determined.

scholarly journals Susceptibility of Mature Staphylococcus Biofilms to Chinese Herbal Decoction Sanhuang Jiedu: An In Vitro Study

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Shaoe Zhang ◽  
Xiao Wang ◽  
Xiaotao Shi ◽  
Honglue Tan ◽  
Himanshu Garg
Keyword(s):  
Laser Scanning ◽  
Multidrug Resistant ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Control Group ◽  
Antibiofilm Activity ◽  
Dependent Manner ◽  
Chinese Herbal ◽  
Titanium Surfaces

Background. External socking and washing with the Chinese herbal Sanhuang Jiedu decoction (SHJD) can effectively control local limb infections with bone and implant exposure. However, the antibiofilm activities of this decoction in vitro have not yet been investigated. Therefore, the aim of this study was to examine the effects and characteristics of SHJD on the mature biofilms of multidrug-resistant staphylococci on a titanium surface. Methods. Biofilm-forming methicillin-resistant Staphylococcus epidermidis ATCC 35984 and S. aureus ATCC 43330, and non-biofilm-forming S. epidermidis ATCC 12228 were selected as the experimental strains. The mature biofilms were prepared on titanium surfaces. The five experimental groups were based on dilution concentrations (DC) of SHJD: the control group (biofilm incubated with 0.85% NaCl solution), the SHJD (DC:1/8) group (initial SHJD solution was diluted 1/8), the SHJD (DC:1/4) group, the SHJD (DC:1/2) group, and the SHJD (DC:1/1) group (initial SHJD solution). The effects of SHJD on the mature biofilms were observed with the bacterial spread plate method, crystal violet (CV) staining, scanning electron microscopy, and confocal laser scanning microscopy. Results. After culture in tryptic soy broth for 72 h, ATCC 43300 and ATCC 35984 produced mature biofilms and ATCC 12228 did not. The optical density value of ATCC 12228 was 0.11 ± 0.02 , significantly lower than that of ATCC 35984 ( 0.42 ± 0.05 ) or ATCC 43300 ( 0.41 ± 0.03 ) ( P < 0.05 ). The mature biofilms of ATCC 43300 and ATCC 35984 clearly disintegrated when incubated for 12–24 h with SHJD (DC:1/1) or SHJD (DC:1/2), showing only scattered bacterial adhesion. In the SHJD (DC:1/4) group, although many residual bacterial colonies still clustered together, presenting a biofilm structure, it was very looser than that in the SHJD (DC:1/8) group in which the biofilm was similar to that in the control group. For ATCC 12228, only colony adhesion was observed, and the number of colonies decreased as the concentration of SHJD or the culture period increased. The quantitative results for the bacterial spread plate and CV staining showed significant differences between the SHJD groups ( P < 0.05 ). Conclusion. SHJD has antibiofilm activity against multidrug-resistant Staphylococcus strains. It weakens or disrupts already-formed mature biofilms on titanium surfaces in a concentration- and incubation time-dependent manner.

scholarly journals Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Ashley N. Brown ◽  
George L. Drusano ◽  
Jonathan R. Adams ◽  
Jaime L. Rodriquez ◽  
Kalyani Jambunathan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Pharmacokinetic Parameters ◽  
Optimal Dosage ◽  
Dependent Manner ◽  
Once Daily ◽  
Content Type ◽  
Toxicity Relationship

ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. IMPORTANCE The emergence and spread of multidrug-resistant M. tuberculosis are a major threat to global public health. Linezolid is an oxazolidinone that is licensed for human use and has demonstrated potent activity against multidrug-resistant M. tuberculosis. However, long-term use of linezolid has shown to be toxic in patients, often resulting in thrombocytopenia. We examined therapeutic linezolid regimens in an in vitro model to characterize the exposure-toxicity relationship. The antibacterial activity against M. tuberculosis was also assessed for these regimens, including the amplification or suppression of resistant mutant subpopulations by the chosen regimen. Higher exposures of linezolid resulted in greater antibacterial activity, but with more toxicity and, for some regimens, increased resistant mutant subpopulation amplification, illustrating the trade-off between activity and toxicity. These findings can provide valuable insight for designing optimal dosage regimens for linezolid that are part of the long combination courses used to treat multidrug-resistant M. tuberculosis.

scholarly journals Indole Derivatives Obtained from Egyptian Enterobacter sp. Soil Isolates Exhibit Antivirulence Activities against Uropathogenic Proteus mirabilis

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 363
Author(s):  
Mai A. Amer ◽  
Reham Wasfi ◽  
Ahmed S. Attia ◽  
Mohamed A. Ramadan
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Multidrug Resistant ◽  
P Value ◽  
Antibiofilm Activity ◽  
Dependent Manner ◽  
Indole Derivatives ◽  
New Treatment ◽  
Tract Infections

Proteus mirabilis is a frequent cause of catheter associated urinary tract infections (CAUTIs). Several virulence factors contribute to its pathogenesis, but swarming motility, biofilm formation, and urease activity are considered the hallmarks. The increased prevalence in antibiotic resistance among uropathogens is alarming and requires searching for new treatment alternatives. With this in mind, our study aims to investigate antivirulence activity of indole derivatives against multidrug resistant P. mirabilis isolates. Ethyl acetate (EtOAc) extracts from Enterobacter sp. (rhizobacterium), isolated from Egyptian soil samples were tested for their ability to antagonize the virulence capacity and biofilm activity of P. mirabilis uropathogens. Extracts of two Enterobacter sp. isolates (coded Zch127 and Cbg70) showed the highest antivirulence activities against P. mirabilis. The two promising rhizobacteria Zch127 and Cbg70 were isolated from soil surrounding: Cucurbita pepo (Zucchini) and Brassica oleracea var. capitata L. (Cabbage), respectively. Sub-minimum inhibitory concentrations (Sub-MICs) of the two extracts showed potent antibiofilm activity with significant biofilm reduction of ten P. mirabilis clinical isolates (p-value < 0.05) in a dose-dependent manner. Interestingly, the Zch127 extract showed anti-urease, anti-swarming and anti-swimming activity against the tested strains. Indole derivatives identified represented key components of indole pyruvate, indole acetamide pathways; involved in the synthesis of indole acetic acid. Additional compounds for indole acetonitrile pathway were detected in the Zch127 extract which showed higher antivirulence activity. Accordingly, the findings of the current study model the feasibility of using these extracts as promising antivirulence agent against the P. mirabilis uropathogens and as potential therapy for treatment of urinary tract infections (UTIs).

scholarly journals Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (9) ◽  
pp. 1398 ◽  
Author(s):  
Yuan Liu ◽  
Jingru Shi ◽  
Ziwen Tong ◽  
Yuqian Jia ◽  
Kangni Yang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antibacterial Activity ◽  
Broad Spectrum ◽  
Multidrug Resistant ◽  
Drug Candidate ◽  
Resistant Bacteria ◽  
Dependent Manner ◽  
Gram Negative ◽  
E Coli ◽  
Amphiphilic Peptide

The emergence and prevalence of multidrug-resistant (MDR) bacteria particularly Gram-negative bacteria presents a global crisis for human health. Colistin and tigecycline were recognized as the last resort of defenses against MDR Gram-negative pathogens. However, the emergence and prevalence of MCR or Tet(X)-mediated acquired drug resistance drastically impaired their clinical efficacy. It has been suggested that antimicrobial peptides might act a crucial role in combating antibiotic resistant bacteria owing to their multiple modes of action and characteristics that are not prone to developing drug resistance. Herein, we report a safe and stable tryptophan-rich amphiphilic peptide termed WRK-12 with broad-spectrum antibacterial activity against various MDR bacteria, including MRSA, colistin and tigecycline-resistant Escherichia coli. Mechanistical studies showed that WRK-12 killed resistant E. coli through permeabilizing the bacterial membrane, dissipating membrane potential and triggering the production of reactive oxygen species (ROS). Meanwhile, WRK-12 significantly inhibited the formation of an E. coli biofilm in a dose-dependent manner. These findings revealed that amphiphilic peptide WRK-12 is a promising drug candidate in the fight against MDR bacteria.

scholarly journals THE ANTIBIOFILM ACTIVITY OF HIBISCUS SABDRIFFA L. AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

2021 ◽  
Vol 52 (3) ◽  
pp. 626-631
Author(s):  
Jaddoa & Gharb
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Ethanolic Extract ◽  
Diffusion Method ◽  
Antibiofilm Activity ◽  
Dependent Manner ◽  
Hibiscus Sabdariffa ◽  
Methicillin Resistant

The current study was aimed to investigate the antibacterial and antibiofilm activity of ethanolic extract of Hibiscus sabdariffa L. calyx against locally isolated methicillin-resistant Staphylococcus aureus (MRSA) at different concentrations were started from 0.078 to 40 mg/ml. The extract was prepared by soaked calyces powder of Hibiscus sabdariffa L. with 80% ethanol in the Soxhlet extraction unit, and then it was aseptically filtered. The antibacterial activity was tested by agar diffusion method and broth microdilution method, this method was used to determine the minimum inhibitory concentration of extract, while the antibiofilm activity was determined by using 96-well polystyrene microtiter plates. The results revealed that the ethanolic extract has antibacterial activity in a concentration-dependent manner, the average diameter zone of inhibition observed against MRSA isolates ranged from 14±0.5 mm to 20±0.5 mm Moreover, at sub-inhibitory concentration, this extract developed an isolate-specific antibiofilm effect and presented highly significant (P< 0.05) variability in biofilm formation before and after addition of ethanolic extract, Mr1, and Mr7 isolates were gave the lowest and highest antibiofilm activity, respectively. In conclusion, the ethanolic extract of H. sabdariffa L. calyx is a promising alternative medication that can be used to treat the infection caused by MRS.

scholarly journals Characterizing the Antimicrobial Activity of N2,N4-Disubstituted Quinazoline-2,4-Diamines toward Multidrug-Resistant Acinetobacter baumannii

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Renee Fleeman ◽  
Kurt S. Van Horn ◽  
Megan M. Barber ◽  
Whittney N. Burda ◽  
David L. Flanigan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Acinetobacter Baumannii ◽  
Alkyl Substituent ◽  
Fold Increase ◽  
Multidrug Resistant ◽  
Antibiofilm Activity ◽  
Gram Negative ◽  
Content Type

ABSTRACT We previously reported a series of N 2,N 4-disubstituted quinazoline-2,4-diamines as dihydrofolate reductase inhibitors with potent in vitro and in vivo antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. In this work, we extended our previous study to the Gram-negative pathogen Acinetobacter baumannii. We determined that optimized N 2,N 4-disubstituted quinazoline-2,4-diamines are strongly antibacterial against multidrug-resistant A. baumannii strains when the 6-position is replaced with a halide or an alkyl substituent. Such agents display potent antibacterial activity, with MICs as low as 0.5 μM, while proving to be strongly bactericidal. Interestingly, these compounds also possess the potential for antibiofilm activity, eradicating 90% of cells within a biofilm at or near MICs. Using serial passage assays, we observed a limited capacity for the development of resistance toward these molecules (4-fold increase in MIC) compared to existing folic acid synthesis inhibitors, such as trimethoprim (64-fold increase) and sulfamethoxazole (128-fold increase). We also identified limited toxicity toward human cells, with 50% lethal doses (LD50s) of ≤23 μM for lead agents 4 and 5. Finally, we demonstrated that our lead agents have excellent in vivo efficacy, with lead agent 5 proving more efficacious than tigecycline in a murine model of A. baumannii infection (90% survival versus 66%), despite being used at a lower dose (2 versus 30 mg kg−1). Together, our results demonstrate that N 2,N 4-disubstituted quinazoline-2,4-diamines have strong antimicrobial and antibiofilm activities against both Gram-positive organisms and Gram-negative pathogens, suggesting strong potential for their development as antibacterial agents.

scholarly journals Antibacterial and Anti-Inflammatory Potential of Polyherbal Formulation Used in Chronic Wound Healing

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ilona Mandrika ◽  
Somit Kumar ◽  
Baiba Zandersone ◽  
Sujith Subash Eranezhath ◽  
Ramona Petrovska ◽  
...  
Keyword(s):  
Wound Healing ◽  
Antibacterial Activity ◽  
Plant Extracts ◽  
Chronic Wound ◽  
Multidrug Resistant ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Clinical Strains ◽  
Anti Inflammatory ◽  
Ethanol Extracts

Objective. Polyherbal formulations Jathyadi Thailam and Jatyadi Ghritam (JT) are used in Indian traditional medicine for diabetic chronic wounds, fistula, fissure, eczema, and burn management. We aimed to investigate the antibacterial and anti-inflammatory properties of crude hexane and ethanol extracts of JT formulations. Methods. Antibacterial activity of JT extracts was tested to estimate minimum inhibitory concentrations (MICs) against nine reference bacterial strains, including one methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) Pseudomonas aeruginosa, and clinical strains of methicillin-susceptible S.aureus (MSSA), all involved in diabetic foot infection. The anti-inflammatory activity of plant extracts was evaluated in LPS-treated macrophage cells by measuring the mRNA levels and secretion of inflammatory mediators. Results. The antibacterial activity of JT extracts was higher against Gram (+) bacteria, with the MICs varying from 1.95 to 62.5 mg/mL. Gram (−) bacteria were only susceptible to ethanol extracts of JT. Plant extracts were found to be the most active against the reference and clinical strains of MSSA, MRSA, and biofilm-forming S. epidermidis. JT extracts efficiently inhibited in a dose-dependent manner the mRNA expression and protein secretion of proinflammatory cytokines IL-6 and IL-1β, and chemokines MCP-1 and CXCL10 in LPS-challenged macrophages. Conclusion. In the present study, we have shown that extracts of JT formulations possess potent antibacterial and anti-inflammatory properties that could be involved in chronic wound healing activity and has the potential to be used as external add-on therapy in the management of multidrug-resistant bacterial infections at the wound.

Design, Facile Synthesis, Antibacterial Activity and Structure-Activity Relationship of Novel Di- and Tri-Substituted 1,3,5-Triazines

2012 ◽  
Vol 9 (3) ◽  
pp. 329-335 ◽  
Author(s):  
Surajit Kumar Ghosh ◽  
Ashmita Saha ◽  
Bornali Hazarika ◽  
Udaya Pratap Singh ◽  
Hans Raj Bhat ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Facile Synthesis ◽  
Structure Activity ◽  
Relationship Of

Biochemical Composition, Antibacterial and Anti-Biofilm Activities of Indian Medicinal Plants

2020 ◽  
Vol 18 ◽  
Author(s):  
Mulugeta Mulat ◽  
Fazlurrahman Khan ◽  
Archana Pandita
Keyword(s):  
Antibacterial Activity ◽  
Medicinal Plants ◽  
Pathogenic Bacteria ◽  
Chemical Constituents ◽  
Multidrug Resistant ◽  
Chloroform Extract ◽  
Acetone Extract ◽  
Biologically Active ◽  
Ocimum Sanctum ◽  
Agar Disc

Background: Medicinal plants have been used for treatments of various health ailments and the practices as a remedial back to thousands of years. Currently, plant-derived compounds used as alternative ways of treatment for multidrug-resistant pathogens. Objective: In the present study, various parts of six medical plants such as Solanum nigrum, Azadirachta indica, Vitex negundo, Mentha arvensis, Gloriosa superba, and Ocimum sanctum were extracted for obtaining biological active constituents. Methods: Soxhlet method of extraction was used for obtaining crude extracts. Agar disc diffusion and 96-well plate spectroscopic reading were used to detect the extract’s antibacterial and antibiofilm properties. Results: The obtained extracts were tested for antimicrobial and antibiofilm properties at 25 mg/mL concentrations. Maximum antibacterial activity was observed in O. sanctum chloroform extract (TUCE) against Staphylococcus aureus (24.33±1.52 mm), S. nigrum acetone extract (MAAC) against Salmonella Typhimurium (12.6 ± 1.5 mm) and Pseudomonas aeruginosa (15.0 ±2.0 mm). Only TUCE exhibited antibacterial activity at least a minimum inhibitory concentration of 0.781 mg/mL. Better antibiofilm activities were also exhibited by petroleum extracts of G. superba (KAPE) and S. nigrum (MAPE) against Escherichia coli, S. Typhimurium, P. aeruginosa and S. aureus. Moreover, S. nigrum acetone extract (MAAC) and O. sanctum chloroform extract (TUCE) were showed anti-swarming activity with a reduction of motility 56.3% against P. aeruginosa and 37.2% against S. aureus. MAAC also inhibits Las A activity (63.3% reduction) in P. aeruginosa. Conclusion: Extracts of TUCE, MAAC, MAPE, and KAPE were exhibited antibacterial and antibiofilm properties against the Gram-positive and Gram-negative pathogenic bacteria. GCMS identified chemical constituents are responsible for being biologically active.

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