scholarly journals Efficacy of Phage- and Bacteriocin-Based Therapies in Combatting Nosocomial MRSA Infections

2021 ◽  
Vol 8 ◽  
Author(s):  
Lauren Walsh ◽  
Crystal N. Johnson ◽  
Colin Hill ◽  
R. Paul Ross
Keyword(s):  
Clinical Trials ◽  
Bacterial Infections ◽  
Food Industry ◽  
Bacterial Resistance ◽  
Randomized Clinical Trials ◽  
Synergistic Effects ◽  
Enzymatic Digestion ◽  
Resistance Development ◽  
Treatment Technologies ◽  
Mrsa Strains

Staphylococcus aureus is a pathogen commonly found in nosocomial environments where infections can easily spread - especially given the reduced immune response of patients and large overlap between personnel in charge of their care. Although antibiotics are available to treat nosocomial infections, the increased occurrence of antibiotic resistance has rendered many treatments ineffective. Such is the case for methicillin resistant S. aureus (MRSA), which has continued to be a threat to public health since its emergence. For this reason, alternative treatment technologies utilizing antimicrobials such as bacteriocins, bacteriophages (phages) and phage endolysins are being developed. These antimicrobials provide an advantage over antibiotics in that many have narrow inhibition spectra, enabling treatments to be selected based on the target (pathogenic) bacterium while allowing for survival of commensal bacteria and thus avoiding collateral damage to the microbiome. Bacterial resistance to these treatments occurs less frequently than with antibiotics, particularly in circumstances where combinatory antimicrobial therapies are used. Phage therapy has been well established in Eastern Europe as an effective treatment against bacterial infections. While there are no Randomized Clinical Trials (RCTs) to our knowledge examining phage treatment of S. aureus infections that have completed all trial phases, numerous clinical trials are underway, and several commercial phage preparations are currently available to treat S. aureus infections. Bacteriocins have primarily been used in the food industry for bio-preservation applications. However, the idea of repurposing bacteriocins for human health is an attractive one considering their efficacy against many bacterial pathogens. There are concerns about the ability of bacteriocins to survive the gastrointestinal tract given their proteinaceous nature, however, this obstacle may be overcome by altering the administration route of the therapy through encapsulation, or by bioengineering protease-resistant variants. Obstacles such as enzymatic digestion are less of an issue for topical/local administration, for example, application to the surface of the skin. Bacteriocins have also shown impressive synergistic effects when used in conjunction with other antimicrobials, including antibiotics, which may allow antibiotic-based therapies to be used more sparingly with less resistance development. This review provides an updated account of known bacteriocins, phages and phage endolysins which have demonstrated an impressive ability to kill S. aureus strains. In particular, examples of antimicrobials with the ability to target MRSA strains and their subsequent use in a clinical setting are outlined.

scholarly journals Tackling Virulence of Pseudomonas aeruginosa by the Natural Furanone Sotolon

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 871
Author(s):  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Ahmed Al Saqr ◽  
Ahmed Alalaiwe ◽  
Hisham A. Abbas ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Therapeutic Agent ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Resistance Development

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.

scholarly journals Targeting Multiple Aminoacyl-tRNA Synthetases Overcomes the Resistance Liabilities Associated with Antibacterial Inhibitors Acting on a Single Such Enzyme

2016 ◽  
Vol 60 (10) ◽  
pp. 6359-6361 ◽  
Author(s):  
Christopher P. Randall ◽  
Dace Rasina ◽  
Aigars Jirgensons ◽  
Alex J. O'Neill
Keyword(s):  
Clinical Trials ◽  
High Frequency ◽  
Drug Targets ◽  
Clinical Utility ◽  
Bacterial Resistance ◽  
Antibacterial Drug ◽  
Resistance Development ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Potential Clinical Utility

ABSTRACTBacterial aminoacyl-tRNA synthetases (aaRSs) represent promising antibacterial drug targets. Unfortunately, the aaRS inhibitors that have to date reached clinical trials are subject to rapid resistance development through mutation, a phenomenon that limits their potential clinical utility. Here, we confirm the intuitively correct idea that simultaneous targeting of two different aaRS enzymes prevents the emergence of spontaneous bacterial resistance at high frequency, a finding that supports the development of multitargeted anti-aaRS therapies.

Combating bacterial resistance by combination of antibiotics with antimicrobial peptides

2019 ◽  
Vol 91 (2) ◽  
pp. 199-209 ◽  
Author(s):  
Dean E. Sheard ◽  
Neil M. O’Brien-Simpson ◽  
John D. Wade ◽  
Frances Separovic
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Synergistic Effects ◽  
Resistance Mechanisms ◽  
Bacterial Strains ◽  
Diverse Range ◽  
Recent Emergence ◽  
Agricultural Industries ◽  
Conventional Antibiotics

Abstract The overuse of antibiotics in the healthcare and agricultural industries has led to the worldwide spread of bacterial resistance. The recent emergence of multidrug resistant (MDR) bacteria has resulted in a call for the development of novel strategies to address this global issue. Research on a diverse range of antimicrobial peptides (AMPs) has shown promising activity against several resistant strains. Increased understanding of the mode of action of AMPs has shown similarity and complementarity to conventional antibiotics and the combination of both has led to synergistic effects in some cases. Combination therapy has been widely used to combat MDR bacterial infections and the recent focus on their application with AMPs may allow antibiotics to be effective against resistant bacterial strains. By conjugation of an antibiotic onto an AMP, a compound may be produced with possibly greater activity and with reduced side-effects and toxicity. The AMP in these conjugates may also act as a unique adjuvant for the antibiotic by disrupting the resistance mechanisms used by bacteria thus allowing the antibiotic to once again be effective. This mini-review outlines some of the current and past work in combining AMPs with conventional antibiotics as strategies to address bacterial resistance.

scholarly journals Dietary Interventions with Polyphenols in Osteoarthritis: A Systematic Review Directed from the Preclinical Data to Randomized Clinical Studies

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1420
Author(s):  
Evdokia Valsamidou ◽  
Aristea Gioxari ◽  
Charalampia Amerikanou ◽  
Panagiotis Zoumpoulakis ◽  
George Skarpas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Synergistic Effects ◽  
Antioxidant Properties ◽  
Research Field ◽  
Clinical Settings ◽  
Dietary Interventions ◽  
Interesting Approach ◽  
Relationship Of

Osteoarthritis (OA) is the most common form of arthritis and a major cause of limited functionality and thus a decrease in the quality of life of the inflicted. Given the fact that the existing pharmacological treatments lack disease-modifying properties and their use entails significant side effects, nutraceuticals with bioactive compounds constitute an interesting field of research. Polyphenols are plant-derived molecules with established anti-inflammatory and antioxidant properties that have been extensively evaluated in clinical settings and preclinical models in OA. As more knowledge is gained in the research field, an interesting approach in the management of OA is the additive and/or synergistic effects that polyphenols may have in an optimized supplement. Therefore, the aim of this review was to summarize the recent literature regarding the use of combined polyphenols in the management of OA. For that purpose, a PubMed literature survey was conducted with a focus on some preclinical osteoarthritis models and randomized clinical trials on patients with osteoarthritis from 2018 to 2021 which have evaluated the effect of combinations of polyphenol-rich extracts and purified polyphenol constituents. Data indicate that combined polyphenols may be promising for the treatment of osteoarthritis in the future, but more clinical trials with novel approaches in the identification of the in-between relationship of such constituents are needed.

scholarly journals Synergistic antibacterial activity of monoterpenes in combination with conventional antimicrobials against Gram-positive and Gram-negative bacteria

2020 ◽  
Vol 19 (2) ◽  
pp. 258
Author(s):  
Maria Helena Pereira de Lira ◽  
Gustavo Fernandes Queiroga Moraes ◽  
Girlene Macena Santos ◽  
Francisco Patrício de Andrade Júnior ◽  
Fillipe De Oliveira Pereira ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Staphylococcus Epidermidis ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Public Health Problem ◽  
New Drugs ◽  
Gram Negative Bacteria ◽  
Microdilution Method

<p><strong>Introduction</strong>: bacterial infections are a public health problem. Besides, the emergence of strains resistant to antimicrobials has<br />contributed to the search for new alternatives, such for the terpenes with antimicrobial potential. <strong>Objectives</strong>: the objective of this<br />study was to determine the possible interaction of isolated monoterpenes (-)-Carveol, Geraniol, Citronellol, α-terpineol, R-(-) Carvone,<br />(-)-Menthol, Linalool, D-Dihydrocarvone, and (-)-Terpine-4-ol with conventional antimicrobials (Chloramphenicol, Minocycline,<br />Amoxicillin and Ciprofloxacin) when they are evaluated on Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis,<br />Escherichia coli and Pseudomonas aeruginosa strains. <strong>Methodology</strong>: the minimum inhibitory concentrations of these test drugs<br />were determined using the microdilution method. The Checkerboard method was used to assess the interactions, by determining<br />the fractional inhibitory concentration index (FIC index). <strong>Results</strong>: aamong the monoterpenes, only Carveol, Citronellol, and Geraniol<br />presented antimicrobial activity (MIC &lt; 1024 μg/mL). They presented synergistic effects against Pseudomonas aeruginosa ATCC-9027<br />(FIC index ≤ 0.5) when in combination with Minocycline. <strong>Conclusion</strong>: this study contributes to the development of new approaches<br />to control bacterial resistance and to the possibility of discovering new drugs.</p>

scholarly journals Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5969
Author(s):  
Doudou Zhang ◽  
Yucheng Cao ◽  
Kaiyi Wang ◽  
Zhuoyue Shi ◽  
Ruodong Wang ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Design Synthesis ◽  
Improper Use ◽  
Compound 21 ◽  
Conventional Antibiotics

The improper use of antibiotics has led to the development of bacterial resistance, resulting in fewer antibiotics for many bacterial infections. Especially, the drug resistance of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) is distinctly serious. This research designed and synthesized two series of 3-substituted ocotillol derivatives in order to improve their anti-HA-MRSA potency and synergistic antibacterial activity. Among the synthesized compounds, 20–31 showed minimum inhibitory concentration (MIC) values of 1–64 µg/mL in vitro against HA-MRSA 18–19, 18–20, and S. aureus ATCC29213. Compound 21 showed the best antibacterial activity, with an MIC of 1 μg/mL and had synergistic inhibitory effects. The fractional inhibitory concentration index (FICI) value was 0.375, when combined with chloramphenicol (CHL) or kanamycin (KAN). The structure–activity relationships (SARs) of ocotillol-type derivatives were also summarized. Compound 21 has the potential to be developed as a novel antibacterial agent or potentiator against HA-MRSA.

scholarly journals Chemical composition and antibacterial activity of commercial copaiba (Copaifera spp.) oils against bacterial pathogens isolated from postoperative mammoplasty surgery

2020 ◽  
Vol 9 (10) ◽  
pp. e1869108593
Author(s):  
Raquel Costa Machado ◽  
Ana Karina Vargas Soares ◽  
Isabela Carvalho dos Santos ◽  
Wanessa de Campos Bortolucci ◽  
Luis Fernando Espinoza Luizar ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Synergistic Effects ◽  
Bacterial Pathogens ◽  
Mass Spectrometry Analysis ◽  
Antibacterial Action ◽  
Gas Chromatography Mass Spectrometry ◽  
Aureus Strain ◽  
Clinical Samples

Plastic surgeries are considered clean or potentially contaminated procedures. The incidence of infection in reduction mammoplasty is 1.1 to 22% and the main etiological agents are bacteria found on the skin and mucous membranes such as Staphylococcus aureus. Due to the increase in bacterial resistance with the widespread use of antibiotics, identify natural compounds with antibacterial action on postoperative surgery wounds are fundamental. Thus, the objective of this research was the identification of compounds and assessment of the antibacterial action of Copaifera spp. (copaiba) oil against standard strains and bacterial pathogens isolated from postoperative mammoplasty surgery. For this, four commercial copaiba oils (1, 2, 3 and 4) were submitted to a gas chromatography/mass spectrometry analysis. The in-vitro antimicrobial activity and the minimum inhibitory concentration (MIC) of oils on standard strains and clinical samples, as well as the disk antibiotics sensitivity and the synergistic effect of the oils and antibiotics, were assessed. A total of 72 compounds were identified, accounting for ~99% of the volatile constituents in the oils. Sesquiterpenes comprised 67.24– 90.11% of the components, with β-caryophyllene being the most common. Oils 1 and 2 were the most active on the S. aureus strain, with MIC similarto Oil 3, while Oil 4presented no activity. The same pattern was observed in the clinical samples. In addition, Oil 2 presented synergism when associated with amoxicillin. The synergistic effects of Copaiba oils may represent a source of therapeutic compounds against bacterial infections in surgical wound.

L-arginine effect on inflammatory mediators: A systematic review of randomized controlled clinical trials

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Seyed Reza Mirhafez ◽  
Mitra Hariri
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Inflammatory Mediators ◽  
Randomized Clinical Trials ◽  
Randomized Controlled Clinical Trials ◽  
Patients With Cancer ◽  
Reactive Protein ◽  
Randomized Controlled ◽  
Human Adults ◽  
Factor Α

Abstract. L-arginine is an important factor in several physiological and biochemical processes. Recently, scientists studied L-arginine effect on inflammatory mediators such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We conducted a systematic review on randomized controlled trials assessing L-arginine effect on inflammatory mediators. We searched data bases including Google scholar, ISI web of science, SCOPUS, and PubMed/Medline up to April 2019. Randomized clinical trials assessing the effect of L-arginine on inflammatory mediators in human adults were included. Our search retrieved eleven articles with 387 participants. Five articles were on patients with cancer and 6 articles were on adults without cancer. L-arginine was applied in enteral form in 5 articles and in oral form in 6 articles. Eight articles were on both genders, two articles were on women, and one article was on men. L-arginine could not reduce inflammatory mediators among patients with and without cancer except one article which indicated that taking L-arginine for 6 months decreased IL-6 among cardiopathic nondiabetic patients. Our results indicated that L-arginine might not be able to reduce selected inflammatory mediators, but for making a firm decision more studies are needed to be conducted with longer intervention duration, separately on male and female and with different doses of L-arginine.

Sign in / Sign up

Export Citation Format

Share Document