scholarly journals Staphylococcal-Produced Bacteriocins and Antimicrobial Peptides: Their Potential as Alternative Treatments for Staphylococcus aureus Infections

Antibiotics ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 40 ◽  
Author(s):  
Logan L. Newstead ◽  
Katarina Varjonen ◽  
Tim Nuttall ◽  
Gavin K. Paterson
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
Genome Mining ◽  
Resistant Bacteria ◽  
Coagulase Negative Staphylococci ◽  
Novel Treatments ◽  
Wide Range ◽  
Almost All

Staphylococcus aureus is an important pathogen of both humans and animals, implicated in a wide range of infections. The emergence of antibiotic resistance has resulted in S. aureus strains that are resistant to almost all available antibiotics, making treatment a clinical challenge. Development of novel antimicrobial approaches is now a priority worldwide. Bacteria produce a range of antimicrobial peptides; the most diverse of these being bacteriocins. Bacteriocins are ribosomally synthesised peptides, displaying potent antimicrobial activity usually against bacteria phylogenetically related to the producer strain. Several bacteriocins have been isolated from commensal coagulase-negative staphylococci, many of which display inhibitory activity against S. aureus in vitro and in vivo. The ability of these bacteriocins to target biofilm formation and their novel mechanisms of action with efficacy against antibiotic-resistant bacteria make them strong candidates as novel therapeutic antimicrobials. The use of genome-mining tools will help to advance identification and classification of bacteriocins. This review discusses the staphylococcal-derived antimicrobial peptides displaying promise as novel treatments for S. aureus infections.

scholarly journals In silicoidentification of novel peptides with antibacterial activity against multidrug resistantStaphylococcus aureus

2019 ◽  
Author(s):  
Linda B Oyama ◽  
Hamza Olleik ◽  
Ana Carolina Nery Teixeira ◽  
Matheus M Guidini ◽  
James A Pickup ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
In Silico ◽  
Multidrug Resistant ◽  
Biofilm Inhibition ◽  
Methicillin Resistant ◽  
Drug Candidates ◽  
Wide Range

AbstractHerein we report the identification and characterisation of two linear antimicrobial peptides (AMPs), HG2 and HG4, with activity against a wide range of multidrug resistant (MDR) bacteria, especially methicillin resistantStaphylococcus aureus(MRSA) strains, a highly problematic group of Gram-positive bacteria in the hospital and community environment. To identify the novel AMPs presented here, we employed the classifier model design, a feature extraction method using molecular descriptors for amino acids for the analysis, visualization, and interpretation of AMP activities from a rumen metagenomic dataset. This allowed for thein silicodiscrimination of active and inactive peptides in order to define a small number of promising novel lead AMP test candidates for chemical synthesis and experimental evaluation.In vitrodata suggest that the chosen AMPs are fast acting, show strong biofilm inhibition and dispersal activity and are efficacious in anin vivomodel of MRSA USA300 infection, whilst showing little toxicity to human erythrocytes and human primary cell linesex vivo. Observations from biophysical AMP-lipid-interactions and electron microscopy suggest that the newly identified peptides interact with the cell membrane and may be involved in the inhibition of other cellular processes. Amphiphilic conformations associated with membrane disruption are also observed in 3D molecular modelling of the peptides. HG2 and HG4 both preferentially bind to MRSA total lipids rather than with human cell lipids indicating that HG4 may form superior templates for safer therapeutic candidates for MDR bacterial infections.Author SummaryWe are losing our ability to treat multidrug resistant (MDR) bacteria, otherwise known as superbugs. This poses a serious global threat to human health as bacteria are increasingly acquiring resistance to antibiotics. There is therefore urgent need to intensify our efforts to develop new safer alternative drug candidates. We emphasise the usefulness of complementing wet-lab andin silicotechniques for the rapid identification of new drug candidates from environmental samples, especially antimicrobial peptides (AMPs). HG2 and HG4, the AMPs identified in our study show promise as effective therapies for the treatment of methicillin resistantStaphylococcus aureusinfections bothin vitroandin vivowhilst having little cytotoxicity against human primary cells, a step forward in the fight against MDR infections.

scholarly journals In Vitro and In Vivo Anti-Salmonella Evaluation of Pectin Extracts and Hydrolysates from “Cas Mango” (Spondias dulcis)

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Denis Zofou ◽  
Golda Lum Shu ◽  
Josepha Foba-Tendo ◽  
Merveille Octavie Tabouguia ◽  
Jules-Clement N. Assob
Keyword(s):  
Multidrug Resistant ◽  
Positive Control ◽  
Resistant Bacteria ◽  
Therapeutic Effects ◽  
Diffusion Technique ◽  
Resistant Strains ◽  
Almost All ◽  
Broth Dilution

Background. The threat to human health posed by multidrug-resistant strains of Salmonella typhi (S. typhi) and Salmonella paratyphi (S. paratyphi) is of growing concern. Generally, there has been increasing resistance and even multidrug resistance to almost all classes of antibiotics. This has rendered treatment with antibiotics difficult and costly. The present study investigated the bioactivity of pectin and pectin hydrolysates derived from a local fruit, Spondias dulcis, against four strains of Salmonellae. Methods. Pectin was extracted from alcohol extractives-free peel by acidic hydrolysis at a temperature of 80°C for one hour at pH 2 and 4. The pectin was precipitated with 95% alcohol at an extract to alcohol ratio of 1:10 v/v. Antimicrobial activity was determined using agar well diffusion technique. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were determined using the broth dilution technique. An in vivo study was then carried out with the bioactive extracts against the most resistant bacteria strain, to fully establish the therapeutic effect of these extracts. Balb/C mice were used, and ciprofloxacin was the positive control antibiotic. The extracts were administered to mice at two doses, 5mg/Kg and 10mg/Kg. The efficacy of extracts in the treatment of typhoid was evaluated based on survival rate, change in body weight, and change in bacteria load. Results. Only one of the extracts (crude pectin pH 2.5) was active against all the Salmonellae by well diffusion, and the growth inhibition varied from 12mm to 15mm at100 μg/ml. Three of the extracts (crude pectin pH 2.5, pH 4, 12h hydrolysate, and pH 4, 1h hydrolysate) had MIC and MBC against all four Salmonellae strains with MIC ranging from 5.68 to 44.45 μg/ml and MBC from 11.36 to 44.45 μg/mL. Three treatments, namely, the pH4-12 hr, hydrolysate at 10mg/Kg and 5mg/Kg, and the pH4-1hr, hydrolysate at 10mg/Kg, had therapeutic effects against Salmonella infection in mice. Conclusion. The present study highlights the potential of pectin oligosaccharides as new source of anti-Salmonella drugs. Further investigations including exploration of mechanism of action of the most active pectin extracts/hydrolysates are envisaged.

Antimicrobial peptides: an overview of a promising class of therapeutics

2007 ◽  
Vol 2 (1) ◽  
pp. 1-33 ◽  
Author(s):  
Andrea Giuliani ◽  
Giovanna Pirri ◽  
Silvia Nicoletto
Keyword(s):  
Antimicrobial Peptides ◽  
Multidrug Resistant ◽  
Innate Immune ◽  
Resistant Bacteria ◽  
Yeast Fungi ◽  
Wide Range ◽  
New Development ◽  
Catheter Site ◽  
Conventional Antibiotics

AbstractAntibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of this class of molecules is their ability to kill multidrug-resistant bacteria. Antimicrobial peptides are relatively small (6 to 100 aminoacids), amphipathic molecules of variable length, sequence and structure with activity against a wide range of microorganisms including bacteria, protozoa, yeast, fungi, viruses and even tumor cells. They usually act through relatively non-specific mechanisms resulting in membranolytic activity but they can also stimulate the innate immune response. Several peptides have already entered pre-clinical and clinical trials for the treatment of catheter site infections, cystic fibrosis, acne, wound healing and patients undergoing stem cell transplantation. We review the advantages of these molecules in clinical applications, their disadvantages including their low in vivo stability, high costs of production and the strategies for their discovery and optimization.

scholarly journals The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Amy B. Howell ◽  
Doris H. D'Souza
Keyword(s):  
Antimicrobial Activity ◽  
Foodborne Pathogens ◽  
Clinical Results ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Oral Bacteria ◽  
Resistant Bacteria ◽  
Wide Range

Pomegranates have been known for hundreds of years for their multiple health benefits, including antimicrobial activity. The recent surge in multidrug-resistant bacteria and the possibility of widespread global virus pandemics necessitate the need for additional preventative and therapeutic options to conventional drugs. Research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. Nearly every part of the pomegranate plant has been tested for antimicrobial activities, including the fruit juice, peel, arils, flowers, and bark. Many studies have utilized pomegranate peel with success. There are various phytochemical compounds in pomegranate that have demonstrated antimicrobial activity, but most of the studies have found that ellagic acid and larger hydrolyzable tannins, such as punicalagin, have the highest activities. In some cases the combination of the pomegranate constituents offers the most benefit. The positive clinical results on pomegranate and suppression of oral bacteria are intriguing and worthy of further study. Much of the evidence for pomegranates’ antibacterial and antiviral activities against foodborne pathogens and other infectious disease organisms comes fromin vitrocell-based assays, necessitating further confirmation ofin vivoefficacy through human clinical trials.

scholarly journals Natural Variability of In Vitro Adherence to Fibrinogen and Fibronectin Does Not Correlate with In Vivo Infectivity of Staphylococcus aureus

2010 ◽  
Vol 78 (4) ◽  
pp. 1711-1716 ◽  
Author(s):  
Mathilde Ythier ◽  
Jose M. Entenza ◽  
Jacques Bille ◽  
François Vandenesch ◽  
Michèle Bes ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rat Model ◽  
Apparent Paradox ◽  
Gene Redundancy ◽  
Wide Range ◽  
Differential Gene ◽  
Human Host Factors ◽  
The Relationship

ABSTRACT Adherence to fibrinogen and fibronectin plays a crucial role in Staphylococcus aureus experimental endocarditis. Previous genetic studies have shown that infection and carriage isolates do not systematically differ in their virulence-related genes, including genes conferring adherence, such as clfA and fnbA. We set out to determine the range of adherence phenotypes in carriage isolates of S. aureus, to compare the adherence of these isolates to the adherence of infection isolates, and to determine the relationship between adherence and infectivity in a rat model of experimental endocarditis. A total of 133 healthy carriage isolates were screened for in vitro adherence to fibrinogen and fibronectin, and 30 isolates were randomly chosen for further investigation. These 30 isolates were compared to 30 infective endocarditis isolates and 30 blood culture isolates. The infectivities of the carriage isolates, which displayed either extremely low or high adherence to fibrinogen and fibronectin, were tested using a rat model of experimental endocarditis. The levels of adherence to both fibrinogen and fibronectin were very similar for isolates from healthy carriers and members of the two groups of infection isolates. All three groups of isolates showed a wide range of adherence to fibrinogen and fibronectin. Moreover, the carriage isolates that showed minimal adherence and the carriage isolates that showed strong adherence had the same infectivity in experimental endocarditis. Adherence was proven to be important for pathogenesis in experimental endocarditis, but even the least adherent carriage strains had the ability to induce infection. We discuss the roles of differential gene expression, human host factors, and gene redundancy in resolving this apparent paradox.

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 Synthesis and Assessment of Antibacterial Activities of Ruthenium(III) Mixed Ligand Complexes Containing 1,10-Phenanthroline and Guanide

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Atakilt Abebe ◽  
Tizazu Hailemariam
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activities ◽  
Drug Resistant ◽  
E Coli ◽  
Antibiotic Drugs ◽  
Wide Range ◽  
In Vivo Cytotoxicity ◽  
Better Than

In this work, two complexes of ruthenium(III) ([Ru(phen)2Cl2]Cl·2H2O and [Ru(phen)2(G)Cl]2Cl·H2O) were synthesized from 1,10-phenanthroline alone as well as from both 1,10-phenanthroline and guanide. The synthesis was checked using halide test, conductance measurement, and spectroscopic (ICP-OES, FTIR, and UV/Vis) analysis. Their in vitro antibacterial activities were also investigated on two Gram-positive (Staphylococcus aureus (S. aureus) and methicillin resistant Staphylococcus aureus (MRSA)) and two Gram-negative (Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae)) bacteria. These complexes showed wide-range better activities than the commercially available controls (Chloramphenicol and Ciprofloxacin) against even the most drug resistant K. pneumoniae. [Ru(phen)2(G)Cl]2Cl·H2O inhibited S. aureus, MRSA, E. coli, and K. pneumoniae by 17.5%, 27.4%, 16%, and 52%, respectively, better than Chloramphenicol. It also inhibited these pathogens by 5.9%, 5.1%, 2.3%, and 17.2%, respectively, better than Ciprofloxacin. Similarly, [Ru(Phen)2(Cl)2]Cl·2H2O inhibited these pathogens by 11%, 8.7%, 0.1%, and 31.2%, respectively, better than Chloramphenicol. Therefore, after in vivo cytotoxicity investigations, these compounds can be considered as potential antibiotic drugs.

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