scholarly journals Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 327 ◽  
Author(s):  
Mariana Espinosa-Valdés ◽  
Sara Borbolla-Alvarez ◽  
Ana Delgado-Espinosa ◽  
Juan Sánchez-Tejeda ◽  
Anabelle Cerón-Nava ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Active Sites ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Biofilm Inhibition ◽  
Amide Derivatives ◽  
Long Chain

Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.

scholarly journals Rhamnolipids Nano-Micelles as a Potential Hand Sanitizer

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 751
Author(s):  
Marwa Reda Bakkar ◽  
Ahmed Hassan Ibrahim Faraag ◽  
Elham R. S. Soliman ◽  
Manar S. Fouda ◽  
Amir Mahfouz Mokhtar Sarguos ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Active Sites ◽  
Specific Interaction ◽  
Virus Transmission ◽  
Multidrug Resistant ◽  
Future Perspective ◽  
Resistant Bacteria ◽  
In Silico Studies

COVID-19 is a pandemic disease caused by the SARS-CoV-2, which continues to cause global health and economic problems since emerging in China in late 2019. Until now, there are no standard antiviral treatments. Thus, several strategies were adopted to minimize virus transmission, such as social distancing, face covering protection and hand hygiene. Rhamnolipids are glycolipids produced formally by Pseudomonas aeruginosa and as biosurfactants, they were shown to have broad antimicrobial activity. In this study, we investigated the antimicrobial activity of rhamnolipids against selected multidrug resistant bacteria and SARS-CoV-2. Rhamnolipids were produced by growing Pseudomonas aeruginosa strain LeS3 in a new medium formulated from chicken carcass soup. The isolated rhamnolipids were characterized for their molecular composition, formulated into nano-micelles, and the antibacterial activity of the nano-micelles was demonstrated in vitro against both Gram-negative and Gram-positive drug resistant bacteria. In silico studies docking rhamnolipids to structural and non-structural proteins of SARS-CoV-2 was also performed. We demonstrated the efficient and specific interaction of rhamnolipids with the active sites of these proteins. Additionally, the computational studies suggested that rhamnolipids have membrane permeability activity. Thus, the obtained results indicate that SARS-CoV-2 could be another target of rhamnolipids and could find utility in the fight against COVID-19, a future perspective to be considered.

scholarly journals AMPing up the search: An in silico approach to identifying Antimicrobial Peptides (AMPs) with potential anti-biofilm activity

2021 ◽  
Author(s):  
Shreeya Mhade ◽  
Stutee Panse ◽  
Gandhar Tendulkar ◽  
Rohit Awate ◽  
Snehal Kadam ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
In Silico ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
C Protein ◽  
Pilus Biogenesis ◽  
Natural And Synthetic

AbstractAntibiotic resistance is a public health threat, and the rise of multidrug-resistant bacteria, including those that form protective biofilms, further compounds this challenge. Antimicrobial peptides (AMPs) have been recognized for their anti-infective properties, including their ability to target processes important for biofilm formation. However, given the vast array of natural and synthetic AMPs, determining potential candidates for anti-biofilm testing is a significant challenge. In this study, we present an in silico approach, based on open-source tools, to identify AMPs with potential anti-biofilm activity. This approach is developed using the sortase-pilin machinery, important for adhesion and biofilm formation, of the multidrug-resistant, biofilm-forming pathogen C. striatum as the target. Using homology modeling, we modeled the structure of the C. striatum sortase C protein, resembling the semi-open lid conformation adopted during pilus biogenesis. Next, we developed a structural library of 5544 natural and synthetic AMPs from sequences in the DRAMP database. From this library, AMPs with known anti-Gram positive activity were filtered, and 100 select AMPs were evaluated for their ability to interact with the sortase C protein using in-silico molecular docking. Based on interacting residues and docking scores, we built a preference scale to categorize candidate AMPs in order of priority for future in vitro and in vivo biofilm studies. The considerations and challenges of our approach, and the resources developed, which includes a search-enabled repository of predicted AMP structures and protein-peptide interaction models relevant to biofilm studies (B-AMP), can be leveraged for similar investigations across other biofilm targets and biofilm-forming pathogens.

scholarly journals Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

2015 ◽  
Vol 59 (6) ◽  
pp. 3075-3083 ◽  
Author(s):  
Brandon J. H. Banaschewski ◽  
Edwin J. A. Veldhuizen ◽  
Eleonora Keating ◽  
Henk P. Haagsman ◽  
Yi Y. Zuo ◽  
...  
Keyword(s):  
Bacterial Pneumonia ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Exogenous Surfactant ◽  
Resistant Bacteria ◽  
Biophysical Properties ◽  
Surfactant Mixtures ◽  
Content Type

ABSTRACTAntibiotic-resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a “perfect storm” for multidrug-resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, since they have potent broad-spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is coadministration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways and opening of collapsed lung regions. The objective of this study was to test various surfactant-AMP mixtures with regard to maintaining pulmonary surfactant biophysical properties and bactericidal functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL-37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant-AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against methillicin-resistantStaphylococcus aureusandPseudomonas aeruginosa. All AMP/surfactant mixtures exhibited an increase of spreading compared to a BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus the BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. The BLES+CATH-2 mixture appears to be an optimal surfactant-AMP mixture based onin vitroassays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.

Bioactivity of Phenolic Compounds Extracted from Strawberry against Formation of Pseudomonas aeruginosa Biofilm

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Baydaa Hussein ◽  
Zainab A. Aldhaher ◽  
Shahrazad Najem Abdu-Allah ◽  
Adel Hamdan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phenolic Compounds ◽  
Biofilm Formation ◽  
Opportunistic Infections ◽  
Formation Rate ◽  
Hydrocarbon Chain ◽  
Health Concern ◽  
Gas Chromatography Mass Spectrometry ◽  
Phenolic Contents

Background: Biofilm is a bacterial way of life prevalent in the world of microbes; in addition to that it is a source of alarm in the field of health concern. Pseudomonas aeruginosa is a pathogenic bacterium responsible for all opportunistic infections such as chronic and severe. Aim of this study: This paper aims to provide an overview of the promotion of isolates to produce a biofilm in vitro under special circumstances, to expose certain antibiotics to produce phenotypic evaluation of biofilm bacteria. Methods and Materials: Three diverse ways were used to inhibited biofilm formation of P.aeruginosa by effect of phenolic compounds extracts from strawberries. Isolates produced biofilm on agar MacConkey under certain circumstances. Results: The results showed that all isolates were resistant to antibiotics except sensitive to azithromycin (AZM, 15μg), and in this study was conducted on three ways to detect the biofilm produced, has been detected by the biofilm like Tissue culture plate (TCP), Tube method (TM), Congo Red Agar (CRA). These methods gave a clear result of these isolates under study. Active compounds were analyzed in both extracts by Gas Chromatography-mass Spectrometry which indicate High molecular weight compound with a long hydrocarbon chain. Conclusion: Phenolic compounds could behave as bioactive material and can be useful to be used in pharmaceutical synthesis. Phenolic contents which found in leaves and fruits extracts of strawberries shows antibacterial activity against all strains tested by the ability to reduce the production of biofilm formation rate.

Effects of Probiotics in the Management of Infected Chronic Wounds: From Cell Culture to Human Studies

2020 ◽  
Vol 15 (3) ◽  
pp. 193-206
Author(s):  
Brognara Lorenzo ◽  
Salmaso Luca ◽  
Mazzotti Antonio ◽  
Di M. Alberto ◽  
Faldini Cesare ◽  
...  
Keyword(s):  
Chronic Wounds ◽  
Animal Experiments ◽  
Multidrug Resistant ◽  
Preliminary Evidence ◽  
Human Studies ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Keywords Probiotics

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

scholarly journals In vitro biological activity of Hydroclathrus clathratus and its use as an extracellular bioreductant for silver nanoparticle formation

2020 ◽  
Vol 9 (1) ◽  
pp. 416-428 ◽  
Author(s):  
Raghad R. Alzahrani ◽  
Manal M. Alkhulaifi ◽  
Nouf M. Al-Enazi
Keyword(s):  
Biological Activity ◽  
Unsaturated Fatty Acids ◽  
Multidrug Resistant ◽  
Chemical Components ◽  
Resistant Bacteria ◽  
Transmission Electron ◽  
Hydroclathrus Clathratus ◽  
Adaptive Nature ◽  
First Time

AbstractThe adaptive nature of algae results in producing unique chemical components that are gaining attention due to their efficiency in many fields and abundance. In this study, we screened the phytochemicals from the brown alga Hydroclathrus clathratus and tested its ability to produce silver nanoparticles (AgNPs) extracellularly for the first time. Lastly, we investigated its biological activity against a variety of bacteria. The biosynthesized nanoparticles were characterized by UV-visible spectroscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, transmission electron microscopy, and energy-dispersive spectroscopy. The biological efficacy of AgNPs was tested against eighteen different bacteria, including seven multidrug-resistant bacteria. Phytochemical screening of the alga revealed the presence of saturated and unsaturated fatty acids, sugars, carboxylic acid derivatives, triterpenoids, steroids, and other components. Formed AgNPs were stable and ranged in size between 7 and 83 nm and presented a variety of shapes. Acinetobacter baumannii, Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), and MDR A. baumannii were the most affected among the bacteria. The biofilm formation and development assay presented a noteworthy activity against MRSA, with an inhibition percentage of 99%. Acknowledging the future of nano-antibiotics encourages scientists to explore and enhance their potency, notably if they were obtained using green, rapid, and efficient methods.

scholarly journals Pseudomonas aeruginosa PAO 1 In Vitro Time–Kill Kinetics Using Single Phages and Phage Formulations—Modulating Death, Adaptation, and Resistance

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 877
Author(s):  
Ana Mafalda Pinto ◽  
Alberta Faustino ◽  
Lorenzo M. Pastrana ◽  
Manuel Bañobre-López ◽  
Sanna Sillankorva
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Swarming Motility ◽  
Resistance Development ◽  
Healthcare Settings ◽  
Time Kill

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted attention for fighting multidrug-resistant infections. In this work, we characterized five phages showing different lytic spectrums towards clinical isolates. Two of these phages were isolated from the Russian Microgen Sextaphage formulation and belong to the Phikmvviruses, while three Pbunaviruses were isolated from sewage. Different phage formulations for the treatment of P. aeruginosa PAO1 resulted in diversified time–kill outcomes. The best result was obtained with a formulation with all phages, prompting a lower frequency of resistant variants and considerable alterations in cell motility, resulting in a loss of 73.7% in swimming motility and a 79% change in swarming motility. These alterations diminished the virulence of the phage-resisting phenotypes but promoted their growth since most became insensitive to a single or even all phages. However, not all combinations drove to enhanced cell killings due to the competition and loss of receptors. This study highlights that more caution is needed when developing cocktail formulations to maximize phage therapy efficacy. Selecting phages for formulations should consider the emergence of phage-resistant bacteria and whether the formulations are intended for short-term or extended antibacterial application.

scholarly journals The Synergistic Effect of Biosynthesized Silver Nanoparticles and Phage ZCSE2 as a Novel Approach to Combat Multidrug-Resistant Salmonella enterica

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 678
Author(s):  
Abdallah S. Abdelsattar ◽  
Rana Nofal ◽  
Salsabil Makky ◽  
Anan Safwat ◽  
Amera Taha ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Color Change ◽  
Antibacterial Properties ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Mortality And Morbidity ◽  
Novel Approach ◽  
Transmission Electron

The emergence and evolution of antibiotic-resistant bacteria is considered a public health concern. Salmonella is one of the most common pathogens that cause high mortality and morbidity rates in humans, animals, and poultry annually. In this work, we developed a combination of silver nanoparticles (AgNPs) with bacteriophage (phage) as an antimicrobial agent to control microbial growth. The synthesized AgNPs with propolis were characterized by testing their color change from transparent to deep brown by transmission electron microscopy (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). The phage ZCSE2 was found to be stable when combined with AgNPs. Both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated for AgNPs, phage, and their combination. The results indicated that MIC and MBC values were equal to 23 µg/mL against Salmonella bacteria at a concentration of 107 CFU/mL. The combination of 0.4× MIC from AgNPs and phage with Multiplicity of Infection (MOI) 0.1 showed an inhibitory effect. This combination of AgNPs and phage offers a prospect of nanoparticles with significantly enhanced antibacterial properties and therapeutic performance.

scholarly journals In vitro activity of antimicrobial peptide CDP-B11 alone and in combination with colistin against colistin-resistant and multidrug-resistant Escherichia coli

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin S. Witherell ◽  
Jason Price ◽  
Ashok D. Bandaranayake ◽  
James Olson ◽  
Douglas R. Call
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Minimal Media

AbstractMultidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including Escherichia coli #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (mcr-1). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against E. coli #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of E. coli #0346. CDP-B11 with colistin inhibits the growth of E. coli #0346 at ≥ 10× lower colistin concentrations compared to colistin alone in Mueller–Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25 μg/mL) compared to colistin alone (2.5 μg/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2 h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-resistant infections.

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