In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus

Here we report two antimicrobial peptides (AMPs), HG2 and HG4 identified from a rumen microbiome metagenomic dataset, with activity against multidrug-resistant (MDR) bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) strains, a major hospital and community-acquired pathogen. We employed the classifier model design to analyse, visualise, and interpret AMP activities. This approach allowed in silico discrimination of promising lead AMP candidates for experimental evaluation. The lead AMPs, HG2 and HG4, are fast-acting and show anti-biofilm and anti-inflammatory activities in vitro and demonstrated little toxicity to human primary cell lines. The peptides were effective in vivo within a Galleria mellonella model of MRSA USA300 infection. In terms of mechanism of action, HG2 and HG4 appear to interact with the cytoplasmic membrane of target cells and may inhibit other cellular processes, whilst preferentially binding to bacterial lipids over human cell lipids. Therefore, these AMPs may offer additional therapeutic templates for MDR bacterial infections

In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus

Here we report two antimicrobial peptides (AMPs), HG2 and HG4 identified from a rumen microbiome metagenomic dataset, with activity against multidrug-resistant (MDR) bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) strains, a major hospital and community-acquired pathogen. We employed the classifier model design to analyse, visualise, and interpret AMP activities. This approach allowed in silico discrimination of promising lead AMP candidates for experimental evaluation. The lead AMPs, HG2 and HG4, are fast-acting and show anti-biofilm and anti-inflammatory activities in vitro and demonstrated little toxicity to human primary cell lines. The peptides were effective in vivo within a Galleria mellonella model of MRSA USA300 infection. In terms of mechanism of action, HG2 and HG4 appear to interact with the cytoplasmic membrane of target cells and may inhibit other cellular processes, whilst preferentially binding to bacterial lipids over human cell lipids. Therefore, these AMPs may offer additional therapeutic templates for MDR bacterial infections

In silico identification of novel peptides with antibacterial activity against multidrug resistant Staphylococcus aureus

Herein we report the identification and characterisation of two linear antimicrobial peptides (AMPs), HG2 and HG4, with activity against a wide range of multidrug resistant (MDR) bacteria, especially methicillin resistant Staphylococcus aureus (MRSA) strains, a highly problematic group of Gram-positive bacteria in the hospital and community environment. To identify the novel AMPs presented here, we employed the classifier model design, a feature extraction method using molecular descriptors for amino acids for the analysis, visualization, and interpretation of AMP activities from a rumen metagenomic dataset. This allowed for the in silico discrimination of active and inactive peptides in order to define a small number of promising novel lead AMP test candidates for chemical synthesis and experimental evaluation. In vitro data suggest that the chosen AMPs are fast acting, show strong biofilm inhibition and dispersal activity and are efficacious in an in vivo model of MRSA USA300 infection, whilst showing little toxicity to human erythrocytes and human primary cell lines ex vivo. Observations from biophysical AMP-lipid-interactions and electron microscopy suggest that the newly identified peptides interact with the cell membrane and may be involved in the inhibition of other cellular processes. Amphiphilic conformations associated with membrane disruption are also observed in 3D molecular modelling of the peptides. HG2 and HG4 both preferentially bind to MRSA total lipids rather than with human cell lipids indicating that HG4 may form superior templates for safer therapeutic candidates for MDR bacterial infections

Conhecimento vocal e a importância da voz como recurso pedagógico na perspectiva de professores universitários

OBJETIVO: investigar o conhecimento vocal e sua importância como recurso pedagógico em professores universitários. MÉTODOS: participaram 112 docentes, média de 46,60 anos, 35,7% do sexo masculino e 64,3% do feminino, 66,1% doutores. Utilizou-se o questionário Condições de Produção Vocal-Professor, adaptado pela pesquisadora, além da inserção de novas questões abertas e fechadas de interesse para o estudo, as quais foram assinaladas em uma escala analógica de zero a dez. Foram coletadas amostras de voz dos professores e analisadas por avaliação fonoaudiológica. As questões fechadas receberam tratamento estatístico, considerando-se a média das notas autorreferidas, em cada variável pesquisada. Os resultados foram correlacionados a partir das variáveis: sexo e presença/ausência de alteração vocal. Organizaram-se as respostas das questões abertas por similaridade de conteúdo e frequência de ocorrência. RESULTADOS: constatou-se associação significante entre sexo feminino e voz fina, fadiga e perda da voz; presença de distúrbio de voz e autorreferência à voz fraca, rouquidão, voz insuficiente para o trabalho e fadiga vocal. Os professores participaram da pesquisa para colaborar e melhorar a voz na docência; mudariam suas vozes nos aspectos de intensidade, tom e modulação; os recursos vocais mais utilizados em sala de aula foram variação de tom e intensidade, modulação e pausas; e quando a voz está alterada, recorrem ao repouso vocal e à hidratação. Atribuiu-se a média de 9,42 para a voz como recurso pedagógico. CONCLUSÃO: o conhecimento vocal dos participantes foi apropriado e eles avaliaram a voz como recurso pedagógico essencial

Contribution à la valorisation du lactosérum. II. Synthèse du lactitol

International audienc