Biology subjects

Otsuka, H.

Publications and source records attributed to Otsuka, H..

4 recordsLinked to original sources

bioRxiv2024

Identifying Genetic Variations in emm89 Streptococcus pyogenes Linked to Severe Invasive Infections

Streptococcus pyogenes causes mild human infections as well as life-threatening invasive diseases. Since the mutations known to enhance virulence to date account for only half of the severe invasive infections, additional mechanisms/mutations need to be identified. Here, we conducted a genome-wide association study of emm89 S. pyogenes strains to comprehensively identify pathology-related bacterial genetic factors (SNPs, indels, genes, or k-mers). Japanese (n=311) and global (n=666) cohort studies of strains isolated from invasive or non-invasive infections revealed 17 and 1,075 SNPs/indels and 2 and 169 genes, respectively, that displayed associations with invasiveness. We validated one of them, a non-invasiveness-related point mutation, fhuB T218C, by structure predictions and introducing it into a severe invasive strain and confirmed that the mutant showed slower growth in human blood. Thus, we report novel mechanisms that convert emm89 S. pyogenes to an invasive phenotype and a platform for establishing novel treatments and prevention strategies.

microbiology↗

bioRxiv2023

Ribosomal protein mutation suppresses gonadal leader cell migration defects in mig-17/ADAMTS mutants in Caenorhabditis elegans

The migration of the gonadal distal tip cells (DTCs) in Caenorhabditis elegans provides an excellent model for studying the migration of epithelial tubes during organogenesis. Mutations in the mig-17/ADAMTS gene cause misdirected migration of DTCs during gonad formation, resulting in deformed gonad arms. An amino-acid substitution in RPL- 20 corresponding to the mammalian RPL18a/eL20, a component of the 60S ribosomal large subunit, showed a slow growth phenotype and strongly suppressed the mig-17 gonadal defects. Slow-growing mutants clk-1 and clk-2 also suppressed mig-17, although weaker than rlp-20 mutants. MIG-17 recruits FBL-1C/fibulin-1C to the gonadal basement membrane to regulate DTC migration. Reducing the gene dosage of fbl-1 by half partially compromised the suppressor activity of the mutant rpl-20 gene on mig-17. Analysis using the mNeonGreen-FBL-1 reporter revealed that its localization to the gonadal basement membrane was significantly reduced in mig-17, whereas it was recovered to the wild-type levels in mig-17; rpl-20 double mutants. These results indicate that the rpl-20 mutation suppresses mig-17 gonadal defects through dual mechanisms: deceleration of growth rate and enhancement of FBL-1C recruitment to the gonadal basement membrane.

developmental biology↗

bioRxiv2020

Genetic characterization of Streptococcus pyogenes emm 89 strains isolated in Japan from 2011 to 2019

Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes emm89 strains has been increasing in several countries and reported to be linked with a recently emerged clade of emm89 strains, designated clade 3. In Japan, epidemiological and genetic information for emm89 strains remains elusive. In this study, we utilized emm89 strains isolated from both STSS (89 isolates) and non-STSS (72 isolates) infections in Japan from 2011 to 2019, and conducted whole-genome sequencing and comparative analysis, which resulted in classification of a large majority into clade 3 regardless of disease severity. In addition, STSS-associated genes and SNPs were found in clade 3 strains, including mutations of streptokinase (Ska), control of virulence sensor (CovS), serum opacity factor (SOF), sortase (SrtB), and fibronectin-binding protein F1 (PrtF1), and absence of the hylP1 gene encoding hyaluronidase. These findings provide insights into notable genetic features of emm89 strains.

microbiology↗

bioRxiv2016

Neurons in the inferior temporal cortex of macaque monkeys are sensitive to multiple surface features from natural objects

Object surfaces contain a variety of visual features that help us to recognize them. To understand how this information is represented and processed in the brain, we prepared a set of images from natural object surfaces that maintained surface features but lacked contours. We examined spiking responses of neurons in the inferior temporal (IT) cortex of monkeys, which is a crucial structure needed for visual object recognition. About half of IT neurons responded to surface images with sharp selectivity, indicating that a significant fraction of these neurons contribute to object surface representation in a sparse manner. Responses of IT neurons were susceptible to image manipulations, including color removal, removal of luminance contrasts, and spatial structure degradation. This shows that multiple features are required for IT responses to surface images. Comparing neuronal response properties among IT, visual area 4 (V4), and primary visual cortex (V1) revealed properties of IT neurons that differed from those in the other visual processing regions. Additionally, some neuronal response properties were similar between IT and V4, but differed from those in V1, indicating that responses of IT neurons to surface images are constructed by hierarchical processing throughout the ventral visual pathway.

neuroscience↗