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Nakagawa, C.

Publications and source records attributed to Nakagawa, C..

3 recordsLinked to original sources

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↗

Phenotypic and genomic evidence for transparent cellulose, metabolic diversity, and stable cellulose production in the Acetobacteraceae

The Acetobacteraceae are a family of microbes that use sugars from fruits, beverages and fermented foods to overproduce bacterial nanocellulose (BNC), a living material with broad applications in medicine and industry. Yet, the family has few complete, contiguous genome sequences available. Here, three different strains - a high production strain NQ5, a metabolic engineering host NCIB 8034, and a new isolate DS12 from kombucha were characterized and complete de novo genomes assembled. Initial growth and yield experiments reveal a diversity of carbon source utilization profiles and BNC production rates, with NQ5 achieving the highest yield on glucose and DS12 having the narrowest utilization profile. All strains synthesize optically clear BNC. Genomic evidence assigns the DS12 isolate to Komagataeibacter nataicola, reassigns NCIB 8034 from Komagataeibacter xylinus to Komagataeibacter oboediens, and supports NQ5 as Novacetimonas hansenii. The bcs gene clusters that encode BNC synthesis are also diverse. The highest producing strain, N. hansenii NQ5, has fewer bnc copies than K. oboediens NQ5, indicating that copy number does not explain high productivity. Analysis also reveals the type and frequency of mobile genetic elements. Notably, N. hansenii NQ5 has a paucity of transposons relative to other strains, which could explain the BNC production stability of N. hansenii NQ5 in culture. Thus, this work argues that Acetobacteraceae are metabolically diverse, and provides genomic evidence explaining beneficial BNC production characteristics of N. hansenii NQ5. Therefore, this work provides evidence for selection of appropriate BNC production strains. IMPORTANCEBacterial cellulose is an important material for biomedical applications like wound dressings. This study defines important characteristics of microbes that produce bacterial cellulose, namely their ability to process different sugars and features of their genomes that make cellulose yield more consistent. These findings will aid in the development of better bacterial cellulose production processes.

microbiology↗

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↗