Xisomab 3G3(Oregon Health & Science University)

Myxobacteria produce a variety of bioactive secondary metabolites, and with a wealth of under-researched species they hold vast potential for undiscovered compounds. With the ever-increasing need for new antibiotics, the development of novel therapeutics is vitally important. Therefore, this study aimed to extract and elucidate antimicrobial metabolites from the following myxobacteria: Myxococcus xanthus CA010 and AB022; Corallococcus exiguus DSM 14696T; Myxococcus stipitatus DSM 14675T; and Corallococcus aberystwythensis AB050AT. Metabolite mixtures were extracted in acetone from XAD-16 resin incubated in liquid cultures and analysed using GC-MS. Bioactivity was identified using a growth inhibition assay against a panel of clinically relevant prey species including Gram-positive and Gram-negative bacteria and a fungus. Growth of Klebsiella pneumoniae and Enterococcus faecalis was most affected by the metabolite mixtures and the mixtures from AB022 and AB050AT were effective against the most prey. GC-MS analysis revealed metabolites with roles in the synthesis and degradation of amino acids and fatty acids, but also identified compounds A and B with a diketopiperazine (DKP) core. With previously confirmed bioactivity of compound A, it is suggested that these DKP compounds are contributing to the antimicrobial activity observed. Furthermore, many compounds could not be identified and so these unknowns present further potential for novel bioactive compounds.

Senecavirus A (SVA) is a member of the Picornaviridae family, Senecavirus genus. The outbreak of swine vesicular disease caused by SVA has presented a significant threat to pig husbandry and public health, resulting in substantial economic losses. In this study, recombinant SVA 3AB and 3C proteins were expressed in the prokaryotic system, purified, and utilized to generate eight monoclonal antibodies (mAbs) specific to SVA 3AB or 3C proteins. Three B-cell epitopes recognized by these mAbs were subsequently identified by Western blotting. The mAbs 3G3, 3D6, and 3B7 against 3AB recognize the epitope ⁹⁰NAYDGPKKNS¹⁰⁰; the mAbs 2C10, 2C8, and 2D12 against 3C recognize the epitope ⁷⁵FTHHGLPTDL⁸⁵, and the mAbs 3C4 and 4A11 against 3C recognize the epitope ⁹⁵DQMPARNSRV¹⁰⁵. Moreover, all three epitopes are highly conserved in different SVA strains and are exposed on the surface of 3AB or 3C proteins, potentially representing important B-cell epitopes. This study constitutes the first report of SVA nonstructural protein epitopes, which may be beneficial for developing innovative detection methods and vaccines and for investigating the roles of 3AB and 3C in viral replication.