RESUMEN
Few antifungal agents are currently available for the treatment of fungal infections. Antimicrobial peptides (AMPs), which are natural molecules involved in the innate immune response of many organisms, represent a promising research method because of their broad killing activity. The aim of this study was to assess the activity of a frog AMP, [K3]temporin-SHa, against some species of yeasts and moulds, and to further explore its activity against Candida albicans. MIC determinations were performed according to EUCAST guidelines. Next, the activity of [K3]temporin-SHa against C. albicans was explored using time-killing curve experiments, membrane permeabilization assays, and electron microscopy. Finally, chequerboard assays were performed to evaluate the synergy between [K3]temporin-SHa and amphotericin B or fluconazole. [K3]temporin-SHa was found to be active in vitro against several yeasts with MIC between 5.5 and 45 µM. [K3]temporin-SHa displayed rapid fungicidal activity against C. albicans (inoculum was divided into two in less than an hour and no viable colonies were recovered after 5 h) with a mechanism that could be due to membrane permeabilization. [K3]temporin-SHa was synergistic with amphotericin B against C. albicans (FICI = 0.303). [K3]temporin-SHa could represent an additional tool to treat several Candida species and C. neoformans.
Asunto(s)
Anfotericina B , Antifúngicos , Anfotericina B/farmacología , Antifúngicos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Candida albicans , Fluconazol/farmacología , Pruebas de Sensibilidad Microbiana , LevadurasRESUMEN
Saliva is essential for the maintenance of oral health. When salivary flow is impaired, the risk of various oral diseases such as caries and candidiasis increases drastically. Under healthy conditions, saliva provides effective protection against microbial colonization by the collaborative action of numerous host-defense molecules. This review describes how saliva has been the guideline for the design and characterization of a heterodimeric antimicrobial construct called LFchimera. This construct mimics the helical parts of two antimicrobial domains in the crystal structure of bovine lactoferrin. It shows high antimicrobial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, fungi, and parasites including biowarfare agents such as Bacillus anthracis, Burkholderia pseudomallei, and Yersinia pestis. Further, sublethal concentrations of LFchimera inhibited biofilm formation, the invasiveness of HeLa cells by Yersinia spp., and prevented haemolysis of enteropathogenic Escherichia coli, demonstrating the versatility of these peptides.
Asunto(s)
Antiinfecciosos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Antiprotozoarios/farmacología , Lactoferrina/metabolismo , Animales , Antiinfecciosos/química , Antiinfecciosos/metabolismo , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/metabolismo , Antiprotozoarios/química , Antiprotozoarios/metabolismo , Bovinos , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Lactoferrina/química , Leishmania/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Pruebas de Sensibilidad ParasitariaRESUMEN
Antimicrobial resistance is one of the leading challenges in the human healthcare segment. Advances in antimicrobial resistance have triggered exploration of natural alternatives to stabilize its seriousness. Antimicrobial peptides are small, positively charged oligopeptides that are as potent as commercially available antibiotics against a wide spectrum of organisms, such as Gram-positive bacteria, Gram-negative bacteria, viruses, and fungal strains. In addition to their antibiotic capabilities, these peptides possess anticancer activity, activate the immune response, and regulate inflammation. Peptides have distinct modes of action and fall into various categories due to their amino acid composition. Although antimicrobial peptides specifically target the bacterial cytoplasmic membrane, they can also target the cell nucleus and protein synthesis. Owing to the increasing demand for novel treatments against the threat of antimicrobial resistance, naturally synthesized peptides are a beneficial development concept. Antimicrobial peptides are pervasive and can easily be modified using de-novo synthesis technology. Antimicrobial peptides can be isolated from natural resources such as humans, plants, bacteria, and fungi. This review gives a brief overview of antimicrobial peptides and their diastereomeric composition. Other current trends, the future scope of antimicrobial peptides, and the role of d-amino acids are also discussed, with a specific emphasis on the design and development of new drugs.
Asunto(s)
Aminoácidos/química , Farmacorresistencia Microbiana/efectos de los fármacos , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Membrana Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Desarrollo de Medicamentos , Proteínas Citotóxicas Formadoras de Poros/síntesis química , Biosíntesis de Proteínas/efectos de los fármacos , EstereoisomerismoRESUMEN
INTRODUCTION: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by unresolved inflammation and tissue repair pathologies triggered by repeated organic dust exposure. The aim of the study was to investigate changes in levels of the cathelicidin related antimicrobial peptide (CRAMP), laminin (LAM-A1), selected Toll-like receptors (TLR) and chemokines in experimental HP in mice. MATERIALS AND METHODS: Three and 18-month-old female C57BL/6J mice underwent inhalations of the saline extract of Pantoea agglomerans cells, Gram-negative bacterium common in organic dust and known for its pathogenic impact. The inhalations were repeated daily (28 days). ELISA was used for measuring in lung tissue homogenates concentration of CRAMP, LAM-A1, TLR2, TLR4, TLR8, CXCL9 (chemokine [C-X-C motif] ligand) and CXCL10. RESULTS: Levels of TLR2, TLR4 and CXCL9 were significantly higher in both young and old mice lungs already after 7 days of inhalations, while significant increase of LAM-A1 and CXCL10 was noted after 28 days, compared to untreated samples. TLR8 level was significantly augmented only in young mice. Only CRAMP level significantly declined. Significantly higher TLR8 and CXCL9 concentration in untreated samples were noted in old animals compared to young ones. CONCLUSION: Significant alterations of the examined factors levels indicate their role in HP pathogenesis.
Asunto(s)
Alveolitis Alérgica Extrínseca/metabolismo , Catelicidinas/análisis , Quimiocina CXCL10/análisis , Quimiocina CXCL9/análisis , Laminina/análisis , Receptores Toll-Like/análisis , Administración por Inhalación , Aerosoles , Envejecimiento/metabolismo , Alveolitis Alérgica Extrínseca/etiología , Animales , Péptidos Catiónicos Antimicrobianos , Extractos Celulares/toxicidad , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos C57BL , Pantoea/química , Pantoea/inmunología , Precursores de Proteínas/análisisRESUMEN
Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment. In-vitro studies have revealed that 1,25-dihydroxyvitamin D3 enhances innate immunity by increased expression of various antimicrobial peptides, including cathelicidin, and induction of autophagy of the infected cells thus restricts the intracellular growth of Mycobacterium tuberculosis in macrophages. On the other hand, vitamin D has been shown to suppress the pro-inflammatory cytokine response and enhance the anti-inflammatory response. Supplementation with vitamin D in concert with treatment for TB may be beneficial with respect to minimizing the excessive tissue damage that occurs during the active stage of tuberculosis disease. Several clinical trials have evaluated vitamin D supplementation as an adjunct therapy in the treatment for tuberculosis. However, results are conflicting, owing to variations in dose regimens and outcomes. Further investigations are needed to find the optimal concentration of vitamin D for supplementation with standard anti-TB drugs to optimize treatment, which could help to effectively manage both drug-sensitive and drug-resistant tuberculosis.
Asunto(s)
Suplementos Dietéticos , Factores Inmunológicos/uso terapéutico , Tuberculosis/tratamiento farmacológico , Vitamina D/uso terapéutico , Inmunidad Adaptativa/inmunología , Animales , Ensayos Clínicos como Asunto/métodos , Humanos , Inmunidad Innata/inmunología , Factores Inmunológicos/inmunología , Resultado del Tratamiento , Tuberculosis/inmunología , Vitamina D/inmunologíaRESUMEN
The rapid onset of resistance reduces the efficacy of most conventional antimicrobial drugs and is a general cause of concern for human well-being. Thus, there is great demand for a continuous supply of novel antibiotics to combat this problem. Bacteria-derived antimicrobial peptides (AMPs) have long been used as food preservatives; moreover, prior to the development of conventional antibiotics, these AMPs served as an efficient source of antibiotics. Recently, peptides produced by members of the genus Bacillus were shown to have a broad spectrum of antimicrobial activity against pathogenic microbes. Bacillus-derived AMPs can be synthesized both ribosomally and nonribosomally and can be classified according to peptide biosynthesis, structure, and molecular weight. The precise mechanism of action of these AMPs is not yet clear; however, one proposed mechanism is that these AMPs kill bacteria by forming channels in and (or) disrupting the bacterial cell wall. Bacillus-derived AMPs have potential in the pharmaceutical industry, as well as the food and agricultural sectors. Here, we focus on Bacillus-derived AMPs as a novel alternative approach to antibacterial drug development. We also provide an overview of the biosynthesis, mechanisms of action, applications, and effectiveness of different AMPs produced by members of the Bacillus genus, including several recently identified novel AMPs.