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1.
BMC Microbiol ; 21(1): 105, 2021 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-33832427

RESUMEN

BACKGROUND: The rise of microbial antibiotic resistance is a leading threat to the health of the human population. As such, finding new approaches to tackle these microbes, including development of novel antibiotics is vital. RESULTS: In this study, we mined a rumen eukaryotic metatranscriptomic library for novel Antimicrobial peptides (AMPs) using computational approaches and thereafter characterised the therapeutic potential of the AMPs. We identified a total of 208 potentially novel AMPs from the ruminal eukaryotome, and characterised one of those, namely Lubelisin. Lubelisin (GIVAWFWRLAR) is an α-helical peptide, 11 amino acid long with theoretical molecular weight of 1373.76 D. In the presence of Lubelisin, strains of methicillin-resistant Staphylococcus aureus (MRSA) USA300 and EMRSA-15 were killed within 30 min of exposure with ≥103 and 104 CFU/mL reduction in viable cells respectively. Cytotoxicity of Lubelisin against both human and sheep erythrocytes was low resulting in a therapeutic index of 0.43. Membrane permeabilisation assays using propidium iodide alongside transmission electron microscopy revealed that cytoplasmic membrane damage may contribute to the antimicrobial activities of Lubelisin. CONCLUSIONS: We demonstrate that the rumen eukaryotome is a viable source for the discovery of antimicrobial molecules for the treatment of bacterial infections and further development of these may provide part of the potential solution to the ongoing problem of antimicrobial resistance. The role of these AMPs in the ecological warfare within the rumen is also currently unknown.


Asunto(s)
Eucariontes , Staphylococcus aureus Resistente a Meticilina , Proteínas Citotóxicas Formadoras de Poros , Rumen/parasitología , Animales , Membrana Celular/efectos de los fármacos , Membrana Celular/ultraestructura , Descubrimiento de Drogas , Eritrocitos/efectos de los fármacos , Eucariontes/metabolismo , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/aislamiento & purificación , Proteínas Citotóxicas Formadoras de Poros/farmacología , Transcriptoma
2.
Archaea ; 2014: 841463, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24803846

RESUMEN

The aim of this work was to study whether feeding a methanogen inhibitor from birth of goat kids and their does has an impact on the archaeal population colonizing the rumen and to what extent the impact persists later in life. Sixteen goats giving birth to two kids were used. Eight does were treated (D+) with bromochloromethane after giving birth and over 2 months. The other 8 goats were not treated (D-). One kid per doe in both groups was treated with bromochloromethane (k+) for 3 months while the other was untreated (k-), resulting in four experimental groups: D+/k+, D+/k-, D-/k+, and D-/k-. Rumen samples were collected from kids at weaning and 1 and 4 months after (3 and 6 months after birth) and from does at the end of the treating period (2 months). Pyrosequencing analyses showed a modified archaeal community composition colonizing the rumen of kids, although such effect did not persist entirely 4 months after; however, some less abundant groups remained different in treated and control animals. The different response on the archaeal community composition observed between offspring and adult goats suggests that the competition occurring in the developing rumen to occupy different niches offer potential for intervention.


Asunto(s)
Archaea/clasificación , Archaea/aislamiento & purificación , Biodiversidad , Dieta/métodos , Cabras , Hidrocarburos Halogenados/administración & dosificación , Rumen/microbiología , Animales , Archaea/efectos de los fármacos , Archaea/genética , Estudios Longitudinales , Análisis de Secuencia de ADN
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