Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug‐resistant infections

2022 ◽  
Author(s):  
Yiyun Zhu ◽  
Weijing Hao ◽  
Xia Wang ◽  
Jianhong Ouyang ◽  
Xinyi Deng ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Drug Resistant ◽  
Conventional Antibiotics

scholarly journals The Intestinal Biofilm of Pseudomonas aeruginosa and Staphylococcus aureus Is Inhibited by Antimicrobial Peptides HBD-2 and HBD-3

2021 ◽  
Vol 11 (14) ◽  
pp. 6595
Author(s):  
Alessandra Fusco ◽  
Vittoria Savio ◽  
Debora Stelitano ◽  
Adone Baroni ◽  
Giovanna Donnarumma
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptides ◽  
Opportunistic Infections ◽  
Epithelial Cell Line ◽  
Drug Resistant ◽  
Intestinal Epithelial ◽  
Genes Encoding ◽  
Conventional Antibiotics ◽  
And Staphylococcus Aureus

Background: The intestinal microbiota is a very active microbial community interacting with the host in maintaining homeostasis; it acts in cooperation with intestinal epithelial cells, which protect the host from the external environment by producing a diverse arsenal of antimicrobial peptides (AMPs), including β-defensins-2 and 3 (HBD-2 and HBD-3), considered among the most studied in this category. However, there are some circumstances in which an alteration of this eubiotic state occurs, with the triggering of dysbiosis. In this condition, the microbiota loses its protective power, leading to the onset of opportunistic infections. In this scenario, the emergence of multi-drug resistant biofilms from Pseudomonas aeruginosa and Staphylococcus aureus is very frequent. Methods: We created a Caco-2 intestinal epithelial cell line stably transfected with the genes, encoding HBD-2 and HBD-3, in order to evaluate their ability to inhibit the intestinal biofilm formation of P. aeruginosa and S. aureus. Results: Both HBD-2 and HBD-3 showed anti-biofilm activity against P. aeruginosa and S. aureus. Conclusions: The exploitation of endogenous antimicrobial peptides as a new anti-biofilm therapy, in isolation or in combination with conventional antibiotics, can be an interesting prospect in the treatment of chronic and multi-drug resistant infections.

scholarly journals Anti-Mycobacterial Peptides: From Human to Phage

2015 ◽  
Vol 35 (2) ◽  
pp. 452-466 ◽  
Author(s):  
Tieshan Teng ◽  
Jiafa Liu ◽  
Hongping Wei
Keyword(s):  
Antimicrobial Peptides ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Membrane Pore ◽  
Immune Modulators ◽  
Inflammatory Conditions ◽  
Resistant Tuberculosis ◽  
Conventional Antibiotics ◽  
Cell Envelopes

Mycobacterium tuberculosis is the major pathogen of tuberculosis (TB). With the growing problem of M. tuberculosis resistant to conventional antibiotics, especially multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the need for new TB drugs is now more prominent than ever. Among the promising candidates for anti-TB drugs, anti-mycobacterial peptides have a few advantages, such as low immunogenicity, selective affinity to prokaryotic negatively charged cell envelopes, and diverse modes of action. In this review, we summarize the recent progress in the anti-mycobacterial peptides, highlighting the sources, effectiveness and bactericidal mechanisms of these antimicrobial peptides. Most of the current anti-mycobacterial peptides are derived either from host immune cells, bacterial extraction, or mycobacteriophages. Besides trans-membrane pore formation, which is considered to be the common bactericidal mechanism, many of the anti-mycobacterial peptides have the second non-membrane targets within mycobacteria. Additionally, some antimicrobial peptides play critical roles in innate immunity. However, a few obstacles, such as short half-life in vivo and resistance to antimicrobial peptides, need overcoming before clinical applications. Nevertheless, the multiple functions of anti-mycobacterial peptides, especially direct killing of pathogens and immune-modulators in infectious and inflammatory conditions, indicate that they are promising candidates for future drug development.

scholarly journals Synergy pattern of short cationic antimicrobial peptides against multidrug-resistant Pseudomonas aeruginosa

2019 ◽  
Author(s):  
Serge Ruden ◽  
Annika Rieder ◽  
Thomas Schwartz ◽  
Ralf Mikut ◽  
Kai Hilpert
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Synergistic Effects ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Multi Drug Resistance ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Conventional Antibiotics

AbstractWith the rise of various multi-drug resistance pathogenic bacteria, worldwide health care is under pressure to respond. Conventional antibiotics are failing and the development of novel classes or alternative strategies is a major priority. Antimicrobial peptides (AMPs) can not only kill multi-drug resistant bacteria, but also can be used synergistically with conventional antibiotics. We selected 30 short AMPs from different origins and measured their synergy in combination with Polymyxin B, Piperacillin, Ceftazidime, Cefepime, Meropenem, Imipenem, Tetracycline, Erythromycin, Kanamycin, Tobramycin, Amikacin, Gentamycin, and Ciprofloxacin. In total 403 unique combinations were tested against a multi-drug resistant Pseudomonas aeruginosa isolate (PA910). As a measure of the synergistic effects, fractional inhibitory concentrations (FICs) were determined using microdilution assays with FICs ranges between 0.25 and 2. A high number of combinations between peptides and Polymyxin B, Erythromycin and Tetracycline were found to be synergistic. Novel variants of Indolicidin also showed a high frequency in synergist interaction.

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

2018 ◽  
Vol 25 (21) ◽  
pp. 2503-2519 ◽  
Author(s):  
Anne Kokel ◽  
Marianna Torok
Keyword(s):  
Side Effects ◽  
Antimicrobial Peptides ◽  
Potential Drug ◽  
Green Technologies ◽  
Specific Antibodies ◽  
Structural Modifications ◽  
Drug Candidates ◽  
Induce Resistance ◽  
Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations

2020 ◽  
Vol 20 (14) ◽  
pp. 1264-1273 ◽  
Author(s):  
Bruno Casciaro ◽  
Floriana Cappiello ◽  
Walter Verrusio ◽  
Mauro Cacciafesta ◽  
Maria Luisa Mangoni
Keyword(s):  
Antimicrobial Peptides ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Lead Compounds ◽  
Bacterial Pathogenicity ◽  
Growth Inhibitory ◽  
Resistant Strains ◽  
Conventional Antibiotics

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.

Novel Compound from Flowers of Moringa oleifera Active Against Multi- Drug Resistant Gram-negative Bacilli

2020 ◽  
Vol 20 (1) ◽  
pp. 69-75
Author(s):  
Santi M. Mandal ◽  
Subhanil Chakraborty ◽  
Santanu Sahoo ◽  
Smritikona Pyne ◽  
Samaresh Ghosh ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Moringa Oleifera ◽  
Aqueous Acetic Acid ◽  
Phytochemical Analysis ◽  
Hydroxyl Groups ◽  
Drug Resistant ◽  
Gram Negative ◽  
Isolated Compound ◽  
Conventional Antibiotics

Background: The need for suitable antibacterial agents effective against Multi-drug resistant Gram-negative bacteria is acknowledged globally. The present study was designed to evaluate the possible antibacterial potential of an extracted compound from edible flowers of Moringa oleifera. Methods: Five different solvents were used for preparing dried flower extracts. The most effective extract was subjected to fractionation and further isolation of the active compound with the highest antibacterial effect was obtained using TLC, Column Chromatography and reverse phase- HPLC. Approaches were made for characterization of the isolated compound using FTIR, NMR and Mass spectrometry. Antibacterial activity was evaluated according to the CLSI guidelines. Results: One fraction of aqueous acetic acid extract of M. oleifera flower was found highly effective and more potent than conventional antibiotics of different classes against Multi-drug resistant Gram-negative bacilli (MDR-GNB) when compared. The phytochemical analysis of the isolated compound revealed the presence of hydrogen-bonded amine and hydroxyl groups attributable to unsaturated amides. Conclusion: The present study provided data indicating a potential for use of the flowers extract of M. oleifera in the fight against infections caused by lethal MDR-GNB. Recommendations: Aqueous acetic acid flower extract of M. oleifera is effective, in-vitro, against Gram-negative bacilli. This finding may open a scope in pharmaceutics for the development of new classes of antibiotics.

scholarly journals Synergy between Histone-Derived Antimicrobial Peptides and Conventional Antibiotics

2021 ◽  
Vol 120 (3) ◽  
pp. 143a
Author(s):  
Jane Zen ◽  
Louise E. Darling ◽  
Donald E. Elmore
Keyword(s):  
Antimicrobial Peptides ◽  
Conventional Antibiotics

A quest to the therapeutic arsenal: Novel strategies to combat multidrug-resistant bacteria

2021 ◽  
Vol 21 ◽  
Author(s):  
Priyanka Ashwath ◽  
Akhila Dharnappa Sannejal
Keyword(s):  
Multidrug Resistant ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antimicrobial Drugs ◽  
Short Palindromic Repeat ◽  
Prevention Of Infections ◽  
Resistant Bacterial Strain ◽  
Conventional Antibiotics ◽  
Drug Resistant Strains

: The increasing resistance of the disease-causing pathogens to antimicrobial drugs is a public health concern and a socio-economic burden. The emergence of multi-drug resistant strains has made it harder to treat and combat infectious diseases with available conventional antibiotics. There are currently few effective therapeutic regimens for the successful prevention of infections caused by drug-resistant microbes. The various alternative strategies used in the recent past to decrease and limit antibiotic resistance in pathogens include bacteriophages, vaccines, anti-biofilm peptides, and antimicrobial peptides. However, in this review, we focus on the novel and robust molecular approach of antisense RNA (asRNA) technology and the clustered regulatory interspaced short palindromic repeat (CRISPR)-based antibiotic therapy, which can be exploited to selectively eradicate the drug-resistant bacterial strain in a sequence-specific fashion establishing opportunities in the treatment of multi-drug resistant related infections.

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