Hwang, J.-H. | Search bioRxiv

bioRxiv2020

New Genotypes and Diversity of Orientia tsutsugamushi Isolated from Scrub Typhus Patients in South Korea as Determined by Multilocus Sequence Typing

Orientia tsutsugamushi, an obligate intracellular organism, is the causative agent of scrub typhus, which is endemic in the Asia-Pacific region. No comparative studies on the genotypic properties of O. tsutsugamushi have been performed using multilocus sequence typing (MLST) in South Korea. Here, we characterized 51 clinical isolates from Jeonju, in southwestern Korea, and we compared them to isolates from Thailand, Laos, and Japan. We also identified 10 new alleles and six novel sequence types. Overall, our results suggest that the relative genetic stability and the clonal populations of O. tsutsugamushi strains in South Korea have remained mostly conserved. Author summaryScrub typhus is a life-threatening disease, caused by infection with O. tsutsugamushi, a Gram-negative intracellular bacterium. Approximately one million people are infected globally every year, especially in the Asia-Pacific region. Strains of O. tsutsugamushi are typically distinguished serologically on the basis of sequences of the highly polymorphic 56-kDa outer membrane protein. Multilocus sequence typing (MLST) is a generic typing method that provides a unified bacterial isolate characterization approach that can be used for evolutionary and population studies of bacteria. In this study, we describe the development and application of a MLST scheme that was applied to 51 O. tsutsugamushi isolates. We found 10 new alleles and six new STs, which yielded a total of seven O. tsutsugamushi STs in South Korea. Among seven different STs (ST 48, 93-98), ST 48 account for the largest proportion (49.0%) of O. tsutsugamushi STs in South Korea. With the exception of the appearance of six novel STs, the clonal populations have remained conserved but further study of population structure and evolutionary trends is warranted.

microbiology↗

bioRxiv2019

Salience network atrophy links neuron type-specific degeneration to loss of empathy in frontotemporal dementia

Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs) and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

neuroscience↗