Biology subjects

Tsunoda, S.

Publications and source records attributed to Tsunoda, S..

3 recordsLinked to original sources

bioRxiv2024

The Role of Morphological Adaptability in Vibrio cholerae's Motility and Pathogenicity

Vibrio cholerae, the etiological agent of cholera, exhibits remarkable adaptability to different environmental conditions by undergoing morphological changes that significantly contribute to its pathogenicity and impact the epidemiology of the disease globally. This study investigates the morphological adaptability of the clinically isolated V. cholerae O1 strain, specifically focusing on the motility and pathogenicity differences between the filamentous and original comma-shaped forms within diverse viscosity conditions. Utilizing the El Tor strain of V. cholerae O1, we induced the transformation into the filamentous form and performed a comparative analysis with the canonical comma-shaped morphology. Our approach involved assessing motility patterns, swimming speeds, rotation rates, kinematics, and reversal frequencies through dark-field microscopy and high-speed imaging techniques. The findings reveal that filamentous V. cholerae cell retains enhanced motility in viscous environments. This suggests an evolutionary adaptation enabling survival across a range of habitats, notably the human gastrointestinal tract. Filamentous forms demonstrated increased reversal behavior at mucin interfaces, hinting at an advantage in penetrating the mucus layer. Rabbit intestinal loop assays further showed that both morphological forms exhibit similar fluid accumulation ratios, thus indicating comparable pathogenic potentials. These results underscore the significance of V. choleraes morphological flexibility in adapting to environmental viscosity changes, shedding light on the bacteriums intricate survival and infection strategies. Our study provides critical insights into the dynamics of cholera, underlining the importance of considering bacterial morphology in developing effective cholera control strategies.

microbiology↗

bioRxiv2024

Perinatal ampicillin administration modulates murine bile acid metabolism in vivo - an observational study

Antibiotics are an indispensable tool of modern medicine, yet their impact extends beyond eliminating harmful bacteria to perturbing the commensal bacteria constituting the gut microbiome. This collateral damage is particularly significant in early life when the gut microbiome is still developing. In humans, antibiotic administration during infancy and childhood is associated with various long-term negative health outcomes. However, existing research has predominantly focused on the direct administration of antibiotics to infants, leaving uncertainties about whether indirect antibiotic exposure produces similar effects. Here, we use mouse models to investigate how three distinct routes of exposure to the commonly prescribed broad-spectrum antibiotic ampicillin influences parent and infant metabolism. These methods simulate major modes of both direct and indirect antibiotic exposure: intravenous antibiotic administration to the mother immediately before birth mimicking intrapartum antibiotic prophylaxis, antibiotic use by the mother during lactation, and direct administration to infants mimicking empiric antibiotic treatment for neonatal sepsis. Through untargeted metabolomics of fecal samples from mouse dams and infants, we identified one class of compounds, bile acids and related cholane steroids, as particularly sensitive to ampicillin treatment. Bile acids, produced by the host and extensively modified by the gut microbiome, serve as important mediators in the cross-talk between the microbiota and the host. Here, we detail the coordinated changes in bile acid metabolism in response to a commonly prescribed antibiotic, focusing on dams treated both pre- and postpartum. Additionally, we identify unique bile acids associated with weight gain in infant mice. ImportanceAntibiotics are widely used perinatally, administered to both parents and infants before, during, and after birth. While they can play a life-saving role, antibiotics also result in collateral damage to the beneficial microbes constituting the gut microbiome. These microbes have many important functions, particularly in the metabolism of small molecules in the body. One such group of molecules, bile acids, undergo extensive modifications by bacteria and may act as a "language" through which microbes communicate with the host. This observational study investigates the impact of the commonly prescribed antibiotic ampicillin on the metabolism of these molecules during childbirth. Our results indicate that ampicillin administration pre- or post-partum significantly alters the mothers bile acid metabolism, but has a minimal influence on infant bile acid levels. However, in all cases, ampicillin administration significantly increased infant weight, even when the antibiotic was solely administered to the mother.

pharmacology and toxicology↗

bioRxiv2024

cryo-EM structure of a blue-shifted channelrhodopsin from Klebsormidium nitens.

Channelrhodopsins (ChRs) are light-gated ion channels and invaluable tools for optogenetic applications. Recent developments in multicolor optogenetics, in which different neurons are controlled by multiple colors of light simultaneously, have increased the demand for ChR mutants with more distant absorption wavelengths. Here we report the 2.9 [A]-resolution cryo-electron microscopy structure of a ChR from Klebsormidium nitens (KnChR), which is one of the most blue-shifted ChRs. The structure elucidates the 6-s-cis configuration of the retinal chromophore, indicating its contribution to a distinctive blue shift in action spectra. The unique architecture of the C-terminal region reveals its role in the allosteric modulation of channel kinetics, enhancing our understanding of its functional dynamics. Based on the structure-guided design, we developed mutants with blue-shifted action spectra. Finally, we confirm that UV or deep-blue light can activate KnChR-transfected precultured neurons, expanding its utility in optogenetic applications. Our findings contribute valuable insights to advance optogenetic tools and enable refined capabilities in neuroscience experiments.

biochemistry↗