scholarly journals Anti-Biofilm Activity of the Fungal Phytotoxin Sphaeropsidin A against Clinical Isolates of Antibiotic-Resistant Bacteria

Toxins ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 444
Author(s):  
Emanuela Roscetto ◽  
Marco Masi ◽  
Matilde Esposito ◽  
Roberta Di Lecce ◽  
Antonella Delicato ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Antimicrobial Properties ◽  
Pathogenic Fungi ◽  
Human Infection ◽  
New Drugs ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Clinical Test ◽  
Antibiotic Resistant ◽  
Sphaeropsidin A

Many pathogens involved in human infection have rapidly increased their antibiotic resistance, reducing the effectiveness of therapies in recent decades. Most of them can form biofilms and effective drugs are not available to treat these formations. Natural products could represent an efficient solution in discovering and developing new drugs to overcome antimicrobial resistance and treat biofilm-related infections. In this study, 20 secondary metabolites produced by pathogenic fungi of forest plants and belonging to diverse classes of naturally occurring compounds were evaluated for the first time against clinical isolates of antibiotic-resistant Gram-negative and Gram-positive bacteria. epi-Epoformin, sphaeropsidone, and sphaeropsidin A showed antimicrobial activity on all test strains. In particular, sphaeropsidin A was effective at low concentrations with Minimum Inhibitory Concentration (MIC) values ranging from 6.25 μg/mL to 12.5 μg/mL against all reference and clinical test strains. Furthermore, sphaeropsidin A at sub-inhibitory concentrations decreased methicillin-resistant S. aureus (MRSA) and P. aeruginosa biofilm formation, as quantified by crystal violet staining. Interestingly, mixtures of sphaeropsidin A and epi-epoformin have shown antimicrobial synergistic effects with a concomitant reduction of cytotoxicity against human immortalized keratinocytes. Our data show that sphaeropsidin A and epi-epoformin possess promising antimicrobial properties.

scholarly journals The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 650
Author(s):  
Kylen E. Ridyard ◽  
Joerg Overhage
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Properties ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Peptide Antibiotic ◽  
Adaptive Responses ◽  
Antibiotic Resistant ◽  
Structural Modifications ◽  
Immobilization Techniques ◽  
Conventional Antibiotics

The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use.

scholarly journals An improved and highly selective fluorescence assay for measuring phosphatidylserine decarboxylase activity

2020 ◽  
Vol 295 (27) ◽  
pp. 9211-9222
Author(s):  
Jae-Yeon Choi ◽  
Raymond Black ◽  
HeeJung Lee ◽  
James Di Giovanni ◽  
Robert C. Murphy ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Mammalian Cells ◽  
Large Scale ◽  
Pathogenic Fungi ◽  
Fluorescence Yield ◽  
Resistant Bacteria ◽  
Fluorescence Signal ◽  
Decarboxylase Activity ◽  
Antibiotic Resistant ◽  
Anti Cancer

Phosphatidylserine decarboxylases (PSDs) catalyze the conversion of phosphatidylserine (PS) to phosphatidylethanolamine (PE), a critical step in membrane biogenesis and a potential target for development of antimicrobial and anti-cancer drugs. PSD activity has typically been quantified using radioactive substrates and products. Recently, we described a fluorescence-based assay that measures the PSD reaction using distyrylbenzene-bis-aldehyde (DSB-3), whose reaction with PE produces a fluorescence signal. However, DSB-3 is not widely available and also reacts with PSD's substrate, PS, producing an adduct with lower fluorescence yield than that of PE. Here, we report a new fluorescence-based assay that is specific for PSD and in which the presence of PS causes only negligible background. This new assay uses 1,2-diacetyl benzene/β-mercaptoethanol, which forms a fluorescent iso-indole-mercaptide conjugate with PE. PE detection with this method is very sensitive and comparable with detection by radiochemical methods. Model reactions examining adduct formation with ethanolamine produced stable products of exact masses (m/z) of 342.119 and 264.105. The assay is robust, with a signal/background ratio of 24, and can readily detect formation of 100 pmol of PE produced from Escherichia coli membranes, Candida albicans mitochondria, or HeLa cell mitochondria. PSD activity can easily be quantified by sequential reagent additions in 96- or 384-well plates, making it readily adaptable to high-throughput screening for PSD inhibitors. This new assay now enables straightforward large-scale screening for PSD inhibitors against pathogenic fungi, antibiotic-resistant bacteria, and neoplastic mammalian cells.

scholarly journals A large-scale comparison shows that genetic changes causing antibiotic resistance in experimentally evolved Pseudomonas aeruginosa predict those in naturally evolved bacteria

2019 ◽  
Author(s):  
Samuel J. T. Wardell ◽  
Attika Rehman ◽  
Lois W. Martin ◽  
Craig Winstanley ◽  
Wayne M. Patrick ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Experimental Evolution ◽  
Large Scale ◽  
Genetic Basis ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Health Crisis ◽  
Wide Range

AbstractPseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections. An increasing number of isolates have acquired mutations that make them antibiotic resistant, making treatment more difficult. To identify resistance-associated mutations we experimentally evolved the antibiotic sensitive strain P. aeruginosa PAO1 to become resistant to three widely used anti-pseudomonal antibiotics, ciprofloxacin, meropenem and tobramycin. Mutants were able to tolerate up to 2048-fold higher concentrations of antibiotic than strain PAO1. Genome sequences were determined for thirteen mutants for each antibiotic. Each mutant had between 2 and 8 mutations. There were at least 8 genes mutated in more than one mutant per antibiotic, demonstrating the complexity of the genetic basis of resistance. Additionally, large deletions of up to 479kb arose in multiple meropenem resistant mutants. For all three antibiotics mutations arose in genes known to be associated with resistance, but also in genes not previously associated with resistance. To determine the clinical relevance of mutations uncovered in experimentally-evolved mutants we analysed the corresponding genes in 457 isolates of P. aeruginosa from patients with cystic fibrosis or bronchiectasis as well as 172 isolates from the general environment. Many of the genes identified through experimental evolution had changes predicted to be function-altering in clinical isolates but not in isolates from the general environment, showing that mutated genes in experimentally evolved bacteria can predict those that undergo mutation during infection. These findings expand understanding of the genetic basis of antibiotic resistance in P. aeruginosa as well as demonstrating the validity of experimental evolution in identifying clinically-relevant resistance-associated mutations.ImportanceThe rise in antibiotic resistant bacteria represents an impending global health crisis. As such, understanding the genetic mechanisms underpinning this resistance can be a crucial piece of the puzzle to combatting it. The importance of this research is that by experimentally evolving P. aeruginosa to three clinically relevant antibiotics, we have generated a catalogue of genes that can contribute to resistance in vitro. We show that many (but not all) of these genes are clinically relevant, by identifying variants in clinical isolates of P. aeruginosa. This research furthers our understanding of the genetics leading to resistance in P. aeruginosa and provides tangible evidence that these genes can play a role clinically, potentially leading to new druggable targets or inform therapies.

scholarly journals Targeting antibiotic resistant bacteria with phage reduces bacterial density in an insect host

2019 ◽  
Vol 15 (3) ◽  
pp. 20180895 ◽  
Author(s):  
Lauri Mikonranta ◽  
Angus Buckling ◽  
Matti Jalasvuori ◽  
Ben Raymond
Keyword(s):  
Antibiotic Resistance ◽  
Phage Therapy ◽  
Synergistic Effects ◽  
Low Frequency ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Model Studies ◽  
Evolution Of Resistance ◽  
Insect Gut

Phage therapy is attracting growing interest among clinicians as antibiotic resistance continues becoming harder to control. However, clinical trials and animal model studies on bacteriophage treatment are still scarce and results on the efficacy vary. Recent research suggests that using traditional antimicrobials in concert with phage could have desirable synergistic effects that hinder the evolution of resistance. Here, we present a novel insect gut model to study phage–antibiotic interaction in a system where antibiotic resistance initially exists in very low frequency and phage specifically targets the resistance bearing cells. We demonstrate that while phage therapy could not reduce the frequency of target bacteria in the population during positive selection by antibiotics, it alleviated the antibiotic induced blooming by lowering the overall load of resistant cells. The highly structured gut environment had pharmacokinetic effects on both phage and antibiotic dynamics compared with in vitro : antibiotics did not reduce the overall amount of bacteria, demonstrating a simple turnover of gut microbiota from non-resistant to resistant population with little cost. The results imply moderate potential for using phage as an aid to target antibiotic resistant gut infections, and question the usefulness of in vitro inferences.

scholarly journals Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds in Bryophytes

2021 ◽  
Vol 12 (1) ◽  
pp. 160
Author(s):  
Piergiorgio Cianciullo ◽  
Viviana Maresca ◽  
Sergio Sorbo ◽  
Adriana Basile
Keyword(s):  
Oxidative Stress ◽  
Antibacterial Properties ◽  
Natural Antioxidants ◽  
Antibacterial Activities ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Isolation And Characterization ◽  
State Of Research

Today global health problems such as increased risks of oxidative stress-related diseases and antibiotic resistance are issues of serious concern. Oxidative stress is considered to be the underlying cause of many contemporary pathological conditions such as neurological disorders, ischemia, cancer, etc. Antibiotic-resistant bacteria are a concerning issue in clinical practice, causing an increase in deadly infections. Bryophytes synthesize an outstanding number of secondary metabolites that have shown several potential therapeutic and nutraceutical applications. Research in the field has led to the isolation and characterization of several compounds (flavonoids, terpenoids, and bibenzyls). Some of these compounds have shown promising in vitro antibacterial activities and antioxidant potential comparable to known natural antioxidants such as ascorbic acid and α-tocopherol. However, the process of developing new drugs from naturally occurring molecules is often an impervious path. In this paper, the current state of research of bryophytic antioxidant and antibacterial applications is discussed.

scholarly journals Comparative in vitro efficacy of eight essential oils as antibacterial agents against pathogenic bacteria isolated from pet-turtles

2018 ◽  
Vol 63 (No. 7) ◽  
pp. 335-343 ◽  
Author(s):  
BCJ De Silva ◽  
S. Hossain ◽  
SHMP Wimalasena ◽  
HNKS Pathirana ◽  
PS Dahanayake ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Essential Oils ◽  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Bacterial Species ◽  
Antimicrobial Properties ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Drug Resistant Bacteria

Essential oils are plant extracts that have been used for their antimicrobial properties for centuries. The keeping of turtles as pets exhibits a growing trend worldwide but these animals are known to harbour a range of pathogenic bacteria. In the current study, we assessed eight essential oils as alternative antibacterial agents against nine species of pet turtle-borne Gram-negative bacteria, namely Aeromonas caviae, A. dhakensis, A. hydrophila, Citrobacter freundii, Morganella morganii, Proteus mirabilis, P. vulgaris, Pseudomonas aeruginosa and Salmonella enterica. Except for Pseudomonas aeruginosa, all other bacterial species showed high susceptibility to six essential oils, namely oregano, cinnamon, clove, lemongrass, lavender and eucalyptus oils in descending order of efficacy. Minimum inhibitory concentrations and minimum bactericidal concentrations values of the essential oils against all tested species except for P. aeruginosa showed low heterogeneity, showing that these essential oils can effectively control the growth of nearly all the tested. However, most of the tested bacteria were multiple-antibiotic-resistant as determined in the antibiotic disc diffusion test, with multiple-antibiotic-resistant index values of ≥ 0.2 for most of the strains. Therefore, with regards to their in vitro activity in controlling growth of multi-drug resistant bacteria, we can classify oregano, cinnamon, clove, lemongrass, lavender and eucalyptus essential oils as effective antibacterial agents. Thus, prospective application of these essential oils in controlling and treating these bacteria should be considered.

scholarly journals Anti-infective Effects of a Fish-Derived Antimicrobial Peptide Against Drug-Resistant Bacteria and Its Synergistic Effects With Antibiotic

2020 ◽  
Vol 11 ◽  
Author(s):  
Yue Chen ◽  
Jing Wu ◽  
Honglan Cheng ◽  
Yue Dai ◽  
Yipeng Wang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Peptide ◽  
Synergistic Effects ◽  
Head Kidney ◽  
Resistant Bacteria ◽  
Bacterial Membrane ◽  
Microbial Infection ◽  
Antibiotic Resistant ◽  
Sytox Green

Antimicrobial peptides (AMPs) play pivotal roles in protecting against microbial infection in fish. However, AMPs from topmouth culter (Erythroculter ilishaeformis) are rarely known. In our study, we isolated an AMP from the head kidney of topmouth culter, which belonged to liver-expressed antimicrobial peptide 2 (LEAP-2) family. Topmouth culter LEAP-2 showed inhibitory effects on aquatic bacterial growth, including antibiotic-resistant bacteria, with minimal inhibitory concentration values ranging from 18.75 to 150 μg/ml. It was lethal for Aeromonas hydrophila (resistant to ampicillin), and took less than 60 min to kill A. hydrophila at a concentration of 5 × MIC. Scanning electron microscope (SEM) and SYTOX Green uptake assay indicated that it impaired the integrity of bacterial membrane by eliciting pore formation, thereby increasing the permeabilization of bacterial membrane. In addition, it showed none inducible drug resistance to aquatic bacteria. Interestingly, it efficiently delayed ampicillin-induced drug resistance in Vibrio parahaemolyticus (sensitive to ampicillin) and sensitized ampicillin-resistant bacteria to ampicillin. The chequerboard assay indicated that topmouth culter LEAP-2 generated synergistic effects with ampicillin, indicating the combinational usage potential of topmouth culter LEAP-2 with antibiotics. As expected, topmouth culter LEAP-2 significantly alleviated ampicillin-resistant A. hydrophila infection in vivo, and enhanced the therapeutic efficacy of ampicillin against A. hydrophila in vivo. Our findings provide a fish innate immune system-derived peptide candidate for the substitute of antibiotics and highlight its potential for application in antibiotic-resistant bacterial infection in aquaculture industry.

scholarly journals A Precautionary Approach to Guide the Use of Transition Metal-Based Nanotechnology to Prevent Orthopedic Infections

Materials ◽  
2019 ◽  
Vol 12 (2) ◽  
pp. 314 ◽  
Author(s):  
Marta Bottagisio ◽  
Arianna Lovati ◽  
Fabio Galbusera ◽  
Lorenzo Drago ◽  
Giuseppe Banfi
Keyword(s):  
Uv Light ◽  
Antimicrobial Properties ◽  
Basic Research ◽  
Orthopedic Implants ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Ros Generation ◽  
Antibiotic Resistant ◽  
Almost All

The increase of multidrug-resistant bacteria remains a global concern. Among the proposed strategies, the use of nanoparticles (NPs) alone or associated with orthopedic implants represents a promising solution. NPs are well-known for their antimicrobial effects, induced by their size, shape, charge, concentration and reactive oxygen species (ROS) generation. However, this non-specific cytotoxic potential is a powerful weapon effective against almost all microorganisms, but also against eukaryotic cells, raising concerns related to their safe use. Among the analyzed transition metals, silver is the most investigated element due to its antimicrobial properties per se or as NPs; however, its toxicity raises questions about its biosafety. Even though it has milder antimicrobial and cytotoxic activity, TiO2 needs to be exposed to UV light to be activated, thus limiting its use conjugated to orthopedic devices. By contrast, gold has a good balance between antimicrobial activity as an NP and cytocompatibility because of its inability to generate ROS. Nevertheless, although the toxicity and persistence of NPs within filter organs are not well verified, nowadays, several basic research on NP development and potential uses as antimicrobial weapons is reported, overemphasizing NPs potentialities, but without any existing potential of translation in clinics. This analysis cautions readers with respect to regulation in advancing the development and use of NPs. Hopefully, future works in vivo and clinical trials will support and regulate the use of nano-coatings to guarantee safer use of this promising approach against antibiotic-resistant microorganisms.

scholarly journals Boosting Synergistic Effects of Short Antimicrobial Peptides With Conventional Antibiotics Against Resistant Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Chih-Lung Wu ◽  
Kuang-Li Peng ◽  
Bak-Sau Yip ◽  
Ya-Han Chih ◽  
Jya-Wei Cheng
Keyword(s):  
Antimicrobial Peptides ◽  
Synergistic Effects ◽  
Antibacterial Activities ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
C Terminus ◽  
Global Spread ◽  
Synergistic Mechanism ◽  
Conventional Antibiotics

The global spread of antibiotic-resistant infections has meant that there is an urgent need to develop new antimicrobial alternatives. In this study, we developed a strategy to boost and/or synergize the activity of conventional antibiotics by combination with antimicrobial peptides tagged with the bulky non-natural amino acid β-naphthylalanine (Nal) to their N- or C-terminus. A checkerboard method was used to evaluate synergistic effects of the parent peptide and the Nal-tagged peptides. Moreover, boron-dipyrro-methene labeled vancomycin was used to characterize the synergistic mechanism of action between the peptides and vancomycin on the bacterial strains. These Nal-tagged antimicrobial peptides also reduced the antibiotic-induced release of lipopolysaccharide from Gram-negative bacteria by more than 99.95%. Our results demonstrate that Nal-tagged peptides could help in developing antimicrobial peptides that not only have enhanced antibacterial activities but also increase the synergistic effects with conventional antibiotics against antibiotic-resistant bacteria.

scholarly journals Targeting antibiotic resistant bacteria with phages reduces bacterial density in an insect host

2018 ◽  
Author(s):  
Lauri Mikonranta ◽  
Angus Buckling ◽  
Matti Jalasvuori ◽  
Ben Raymond
Keyword(s):  
Antibiotic Resistance ◽  
Phage Therapy ◽  
Synergistic Effects ◽  
Low Frequency ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Model Studies ◽  
Evolution Of Resistance ◽  
Insect Gut

Phage therapy is attracting growing interest among clinicians as antibiotic resistance continues becoming harder to control. However, clinical trials and animal model studies on bacteriophage treatment are still scarce and results on the efficacy vary. Recent research suggests that using traditional antimicrobials in concert with phage could have desirable synergistic effects that hinder the evolution of resistance. Here, we present a novel insect gut model to study phage-antibiotic interaction in a system where antibiotic resistance initially exists in very low frequency and phage specifically targets the resistance bearing cells. We demonstrate that while phage therapy could not reduce the frequency of target bacteria in the population during positive selection by antibiotics, it alleviated the antibiotic induced blooming by lowering the overall load of resistant cells. The highly structured gut environment had pharmacokinetic effects on both phage and antibiotic dynamics compared to in vitro: antibiotics did not reduce the overall amount of bacteria, demonstrating a simple turnover of gut flora from non-resistant to resistant population with little cost. The results imply moderate potential for using phage as an aid to target antibiotic resistant gut infections, and question the usefulness of in vitro inferences.

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