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Abstract 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.

The association between autosomal dominant cerebellar ataxia (ADCA) and psychosis is little understood. A family was identified with three male members with ADCA, one of whom suffered from a psychotic illness. Detailed neuropsychological testing was undertaken. The aim was to provide a detailed profile of these cases of ADCA, describing preserved abilities and cognitive deficits associated with this condition. It was intended to examine whether distinct differences in profile were apparent between the psychotic and nonpsychotic family members. There were three principal findings. (1) One case, ten years after diagnosis, showed a generalized loss of cognitive function, but with relatively intact memory. (2) The case with a concurrent psychosis differed from the other two cases in showing global memory impairment, as well as generalized impairment in all functions tested. It is probable that the memory impairment is related to the psychotic illness. (3) All three cases showed severe executive dysfunction. Executive dysfunction is common to both ADCA and schizophrenia; it is suggested that these executive deficits are aetiologically related to cerebellar dysfunction in both conditions. [ABSTRACT FROM AUTHOR]