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1. Isolation and characterization of Neisseria musculi sp. nov., from the wild house mouse

Author

Weyand, NJ, Ma, M, Phifer-Rixey, M, Taku, NA, Rendón, MA, Hockenberry, AM, Kim, WJ, Agellon, AB, Biais, N, Suzuki, TA, Sait, LG, Harrison, OB, Bratcher, HB, Nachman, MW, Maiden, MC, and So, M

Abstract

Neisseria have been isolated from or detected in a wide range of animals, from nonhuman primates and felids to a rodent, the guinea pig (Liu et al., 2015). By means of selective culture, biochemical testing, Gram staining and PCR screening for the Neisseria-specific Internal Transcribed Spacer region of the rRNA operon, we isolated four strains of Neisseria from the oral cavity of the wild house mouse, Mus musculus subspecies domesticus. The isolates are highly related and form a separate clade in the genus, as judged by rMLST and core gene tree analyses. One isolate, provisionally named Neisseria musculi sp. nov. (type strain AP2031T = DSM 101846T = CCUG 68283T = LMG 29261T), was studied further. AP2031/N. musculi grows well in vitro. It is naturally competent, taking up DNA in a DUS and pilT-dependent manner, and is amenable to genetic manipulation. These and other genomic attributes of N. musculi make it an ideal candidate for use in developing a mouse model for studying Neisseria-host interactions.

Published
2016

2. Cannabidiol interactions with voltage-gated sodium channels.

Author

Sait LG, Sula A, Ghovanloo MR, Hollingworth D, Ruben PC, and Wallace BA

Subjects
Binding Sites, Cannabidiol pharmacology, Crystallography, X-Ray, Electrophysiology, Protein Conformation, Sequence Alignment, Voltage-Gated Sodium Channels chemistry, Voltage-Gated Sodium Channels drug effects, Voltage-Gated Sodium Channels genetics, Cannabidiol metabolism, Voltage-Gated Sodium Channels metabolism
Abstract

Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels., Competing Interests: LS, AS, MG, DH, PR, BW No competing interests declared, (© 2020, Sait et al.)

Published
2020
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