-
Current Opinion in Biotechnology Jun 2023Antifungal peptides (AFPs) are widely described as promising prospects to treat and prevent fungal infections, though they are far less studied than their antibacterial... (Review)
Review
Antifungal peptides (AFPs) are widely described as promising prospects to treat and prevent fungal infections, though they are far less studied than their antibacterial counterparts. Although promising, AFPs have practical limitations that have hindered their use as therapeutics. Rational design and combinatorial engineering are powerful protein engineering strategies with much potential to address the limitations of AFPs by designing peptides with improved physiochemical and biological characteristics. We examine how rational design and combinatorial engineering approaches have already been used to improve the properties of AFPs and propose key opportunities for applying these strategies to push the design and application of AFPs forward.
Topics: Antifungal Agents; Peptides; Protein Engineering
PubMed: 37028003
DOI: 10.1016/j.copbio.2023.102926 -
Journal of Dairy Science Mar 2022Bioactive peptides derived from milk proteins are widely known to possess antibacterial activities. Even though the antibacterial effects of milk-derived peptides are...
Bioactive peptides derived from milk proteins are widely known to possess antibacterial activities. Even though the antibacterial effects of milk-derived peptides are widely characterized, not much focus is given to their antifungal characterization. Therefore, in this study, we investigated the antifungal properties of camel and cow whey and casein hydrolysates against various species of pathogenic Candida. The hydrolysates were produced using 2 enzymes (alcalase and protease) at differing hydrolysis durations (2, 4, and 6 h) and tested for their antifungal properties. The results showed that intact cow whey and casein proteins did not display any anti-Candida albicans properties, whereas the alcalase-derived 2 h camel casein hydrolysate (CA-C-A2) displayed a higher percentage of inhibition against Candida albicans (93.69 ± 0.26%) followed by the cow casein hydrolysate generated by protease-6 h (Co-C-P6; 81.66 ± 0.99%), which were significantly higher than that of fluconazole, a conventional antifungal agent (76.92 ± 4.72%). Interestingly, when tested again Candida krusei, camel casein alcalase 2 and 4 h (CA-C-A2 and CA-C-A4), and cow whey alcalase-6 h (CO-W-A6) hydrolysates showed higher antifungal potency than fluconazole. However, for Candida parapsilosis only camel casein alcalase-4 h (Ca-C-A4) and cow casein protease-6 h (Co-C-P6) hydrolysates were able to inhibit the growth of C. parapsilosis by 19.31 ± 0.84% and 23.82 ± 4.14%, respectively, which was lower than that shown by fluconazole (29.86 ± 1.11%). Overall, hydrolysis of milk proteins from both cow and camel enhanced their antifungal properties. Camel milk protein hydrolysates were more potent in inhibiting pathogenic Candida species as compared with cow milk protein hydrolysates. This is the first study that highlights the antifungal properties of camel milk protein hydrolysates.
Topics: Animals; Antifungal Agents; Camelus; Candida; Caseins; Cattle; Female; Milk; Milk Proteins; Protein Hydrolysates; Whey; Whey Proteins
PubMed: 34955259
DOI: 10.3168/jds.2021-20944 -
Antimicrobial Agents and Chemotherapy Aug 2021Sporotrichosis has become an important zoonosis in Brazil, and is the primary species transmitted by cats. Improvement of animal treatment will help control and limit...
Sporotrichosis has become an important zoonosis in Brazil, and is the primary species transmitted by cats. Improvement of animal treatment will help control and limit the spread and geographic expansion of sporotrichosis. Accordingly, buparvaquone, an antiprotozoal hydroxynaphthoquinone agent marketed as Butalex, was evaluated and against feline-borne isolates of . Buparvaquone inhibited fungal growth at concentrations 4-fold lower than itraconazole (the first-choice antifungal used for sporotrichosis) and was 408 times more selective for than mammalian cells. Yeasts treated with a subinhibitory concentration of buparvaquone exhibited mitochondrial dysfunction, reactive oxygen species and neutral lipid accumulation, and impaired plasma membranes. Scanning electron microscopy images also revealed buparvaquone altered cell wall integrity and induced cell disruption. experiments in a Galleria mellonella model revealed that buparvaquone (single dose of 5 mg/kg of body weight) is more effective than itraconazole against infections with yeasts. Combined, our results indicate that buparvaquone has a great and antifungal activity against , revealing the potential application of this drug as an alternative treatment for feline sporotrichosis.
Topics: Animals; Antifungal Agents; Cats; Microbial Sensitivity Tests; Naphthoquinones; Sporothrix; Sporotrichosis
PubMed: 34152816
DOI: 10.1128/AAC.00699-21 -
Biomolecules Sep 2019Pyrrolnitrin (PRN) is a microbial pyrrole halometabolite of immense antimicrobial significance for agricultural, pharmaceutical and industrial implications. The compound... (Review)
Review
Pyrrolnitrin (PRN) is a microbial pyrrole halometabolite of immense antimicrobial significance for agricultural, pharmaceutical and industrial implications. The compound and its derivatives have been isolated from rhizospheric fluorescent or non-fluorescent pseudomonads, and . They are known to confer biological control against a wide range of phytopathogenic fungi, and thus offer strong plant protection prospects against soil and seed-borne phytopathogenic diseases. Although chemical synthesis of PRN has been obtained using different steps, microbial production is still the most useful option for producing this metabolite. In many of the plant-associated isolates of and , production of PRN is dependent on the quorum-sensing regulation that usually involves N-acylhomoserine lactone (AHL) autoinducer signals. When applied on the organisms as antimicrobial agent, the molecule impedes synthesis of key biomolecules (DNA, RNA and protein), uncouples with oxidative phosphorylation, inhibits mitotic division and hampers several biological mechanisms. With its potential broad-spectrum activities, low phototoxicity, non-toxic nature and specificity for impacts on non-target organisms, the metabolite has emerged as a lead molecule of industrial importance, which has led to developing cost-effective methods for the biosynthesis of PRN using microbial fermentation. Quantum of work narrating focused research efforts in the emergence of this potential microbial metabolite is summarized here to present a consolidated, sequential and updated insight into the chemistry, biology and applicability of this natural molecule.
Topics: Antifungal Agents; Burkholderia; Fermentation; Fungi; Microbial Sensitivity Tests; Pseudomonas; Pyrrolnitrin; Serratia
PubMed: 31484394
DOI: 10.3390/biom9090443 -
Frontiers in Cellular and Infection... 2021() is an opportunistic human fungal pathogen that can cause severe infection in clinic. Its incidence and mortality rate has been increasing rapidly. Amphotericin B...
() is an opportunistic human fungal pathogen that can cause severe infection in clinic. Its incidence and mortality rate has been increasing rapidly. Amphotericin B (AMB), the clinical golden standard antifungal agent, has severe side effects that limit its clinical application. Thus, lowering the concentration and increasing the efficacy of AMB in a combinatorial antifungal therapy have been pursued by both industry and academia. Here we identify that fingolimod (FTY720), an immunomodulatory drug used for oral treatment of relapsing-remitting multiple sclerosis, can potentiate the efficacy of AMB against growth synergistically. Furthermore, we observe an antifungal efficacy of FTY720 in combination with AMB against diverse fungal pathogens. Intriguingly, cells treated with both drugs are hypersensitive to endothelial endocytosis and macrophage killing. This is later found to be due to the hyperaccumulation of reactive oxygen species and the corresponding increase in activities of superoxide dismutase and catalase in the cells that received combinatorial treatment. Therefore, the combination of AMB and FTY720 provides a promising antifungal strategy.
Topics: Amphotericin B; Antifungal Agents; Candida albicans; Fingolimod Hydrochloride; Humans; Microbial Sensitivity Tests
PubMed: 33968796
DOI: 10.3389/fcimb.2021.627917 -
Microbiology Spectrum Feb 2022We determined the susceptibility of South African Candida auris bloodstream surveillance isolates to manogepix, a novel antifungal, and several registered antifungal...
We determined the susceptibility of South African Candida auris bloodstream surveillance isolates to manogepix, a novel antifungal, and several registered antifungal agents. C. auris isolates were submitted to a reference laboratory between 2016 and 2017. Species identification was confirmed by phenotypic methods. We determined MICs for amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole, and flucytosine using Sensititre YeastOne and manogepix using a modified Clinical and Laboratory Standards Institute broth microdilution method. Clade distribution was determined for a subset of isolates using whole-genome sequencing. Of 394 tested isolates, 357 were resistant to at least 1 antifungal class. The manogepix MIC range was 0.002 to 0.06 μg/mL for 335 isolates with fluconazole monoresistance. Nineteen isolates were resistant to both fluconazole and amphotericin B yet still had low manogepix MICs (range, 0.004 to 0.03 μg/mL). Two isolates from the same patient were panresistant but had manogepix MICs of 0.004 μg/mL and 0.008 μg/mL. Comparing MIC values, manogepix was >3-fold more potent than azoles, 4-fold more potent than echinocandins, and 9-fold more potent than amphotericin B. Of 84 sequenced isolates, the manogepix MIC range for 70 clade III isolates was 0.002 to 0.031 μg/mL, for 13 clade I isolates was 0.008 to 0.031 μg/mL, and for one clade IV isolate, 0.016 μg/mL. Manogepix exhibited potent activity against all isolates, including those resistant to more than one antifungal agent and in three different clades. These data support manogepix as a promising candidate for treatment of C. auris infections. Since C. auris was first detected in South Africa in 2012, health care-associated transmission events and large outbreaks have led to this pathogen accounting for more than 1 in 10 cases of candidemia. A large proportion of South African C. auris isolates are highly resistant to fluconazole but variably resistant to amphotericin B and echinocandins. There is also an emergence of pandrug-resistant C. auris isolates, limiting treatment options. Therefore, the development of new antifungal agents such as fosmanogepix or the use of new combinations of antifungal agents is imperative to the continued effective treatment of C. auris infections. Manogepix, the active moiety of fosmanogepix, has shown excellent activity against C. auris isolates. With the emergence of C. auris isolates that are pandrug-resistant in South Africa, our susceptibility data support manogepix as a promising new drug candidate for treatment of C. auris and difficult-to-treat C. auris infections.
Topics: Aminopyridines; Antifungal Agents; Candida auris; Candidemia; Drug Resistance, Multiple, Fungal; Echinocandins; Fluconazole; Isoxazoles; Microbial Sensitivity Tests; Sepsis; South Africa
PubMed: 35196811
DOI: 10.1128/spectrum.01717-21 -
Advanced Science (Weinheim,... May 2022Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available....
Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available. Microbial metabolites have been a rich source of antimicrobial agents and have inspired the authors to design and obtain potent and selective antifungal agents, poly(DL-diaminopropionic acid) (PDAP) from the ring-opening polymerization of β-amino acid N-thiocarboxyanhydrides, by mimicking ε-poly-lysine. PDAP kills fungal cells by penetrating the fungal cytoplasm, generating reactive oxygen, and inducing fungal apoptosis. The optimal PDAP displays potent antifungal activity with minimum inhibitory concentration as low as 0.4 µg mL against Candida albicans, negligible hemolysis and cytotoxicity, and no susceptibility to antifungal resistance. In addition, PDAP effectively inhibits the formation of fungal biofilms and eradicates the mature biofilms. In vivo studies show that PDAP is safe and effective in treating fungal keratitis, which suggests PDAPs as promising new antifungal agents.
Topics: Antifungal Agents; Candida albicans; Microbial Sensitivity Tests; Peptides; Polymers
PubMed: 35307990
DOI: 10.1002/advs.202104871 -
Molecules (Basel, Switzerland) Apr 2022Chitosan is a biodegradable and biocompatible polysaccharide obtained by partial deacetylation of chitin. This polymer has been gaining increasing popularity due to its... (Review)
Review
Chitosan is a biodegradable and biocompatible polysaccharide obtained by partial deacetylation of chitin. This polymer has been gaining increasing popularity due to its natural origin, favorable physicochemical properties, and multidirectional bioactivity. In agriculture, the greatest hopes are raised by the possibility of using chitosan as a biostimulant, a plant protection product, an elicitor, or an agent to increase the storage stability of plant raw materials. The most important properties of chitosan include induction of plant defense mechanisms and regulation of metabolic processes. Additionally, it has antifungal, antibacterial, antiviral, and antioxidant activity. The effectiveness of chitosan interactions is determined by its origin, deacetylation degree and acetylation pattern, molecular weight, type of chemical modifications, pH, concentration, and solubility. There is a need to conduct research on alternative sources of chitosan, extraction methods, optimization of physicochemical properties, and commercial implementation of scientific progress outcomes in this field. Moreover, studies are necessary to assess the bioactivity and toxicity of chitosan nanoparticles and chitosan conjugates with other substances and to evaluate the consequences of the large-scale use thereof. This review presents the unique properties of chitosan and its derivatives that have the greatest importance for plant production and yield quality as well as the benefits and limitations of their application.
Topics: Antifungal Agents; Chitin; Chitosan; Molecular Weight; Plants
PubMed: 35566152
DOI: 10.3390/molecules27092801 -
Molecules (Basel, Switzerland) Jun 2021Multi-drug resistant pathogens are a rising danger for the future of mankind. Iodine (I) is a centuries-old microbicide, but leads to skin discoloration, irritation, and...
Multi-drug resistant pathogens are a rising danger for the future of mankind. Iodine (I) is a centuries-old microbicide, but leads to skin discoloration, irritation, and uncontrolled iodine release. Plants rich in phytochemicals have a long history in basic health care. Miller (AV) and L. (Sage) are effectively utilized against different ailments. Previously, we investigated the antimicrobial activities of smart triiodides and iodinated AV hybrids. In this work, we combined iodine with Sage extracts and pure AV gel with polyvinylpyrrolidone (PVP) as an encapsulating and stabilizing agent. Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-Vis), Surface-Enhanced Raman Spectroscopy (SERS), microstructural analysis by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-Ray-Diffraction (XRD) analysis verified the composition of AV-PVP-Sage-I. Antimicrobial properties were investigated by disc diffusion method against 10 reference microbial strains in comparison to gentamicin and nystatin. We impregnated surgical sutures with our biohybrid and tested their inhibitory effects. AV-PVP-Sage-I showed excellent to intermediate antimicrobial activity in discs and sutures. The iodine within the polymeric biomaterial AV-PVP-Sage-I and the synergistic action of the two plant extracts enhanced the microbial inhibition. Our compound has potential for use as an antifungal agent, disinfectant and coating material on sutures to prevent surgical site infections.
Topics: Aloe; Anti-Bacterial Agents; Antifungal Agents; Gentamicins; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Nystatin; Plant Extracts; Povidone; Salvia; Salvia officinalis; Spectrometry, X-Ray Emission; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 34200814
DOI: 10.3390/molecules26123553 -
Japanese Journal of Infectious Diseases May 2022Data on antifungal utilization trends are important for encouraging antifungal stewardship. This study explored the use of antifungal agents for systemic application and...
Data on antifungal utilization trends are important for encouraging antifungal stewardship. This study explored the use of antifungal agents for systemic application and the impact of reimbursement policy changes in Australia. We analyzed national data from the Australian Pharmaceutical Benefits Scheme (PBS) (2005-2016) and determined patterns of use over time and the impact of reimbursement decisions using an interrupted time-series model. From 2005-2016, there was an increase in the use of most antifungals, especially fluconazole, itraconazole, and posaconazole. Ketoconazole was the most commonly dispensed systemic antifungal agent (46.0%) prior to being removed from the PBS list and being replaced by fluconazole (69.8%). The PBS event "Fluconazole and itraconazole restrictions eased" led to the immediate increased use of fluconazole (0.025/1,000 per day), with both the highest rates and numerical increases attributed to obstetricians and gynecologists (1,969%; 1,851 dispensed prescriptions), as well as dermatologists (1,723%; 1,689 dispensed prescriptions) in 2010 and 2016. This is the first Australian national longitudinal estimate of systemic antifungal use. Our findings show an overall increase in the prescription of most antifungals during the investigated period, with reimbursement decisions impacting utilization. These data provide a baseline to inform the development of national antifungal guidelines and policies to encourage more targeted antifungal stewardship.
Topics: Antifungal Agents; Australia; Fluconazole; Itraconazole
PubMed: 34588371
DOI: 10.7883/yoken.JJID.2021.505