Episymbiotic Saccharibacteria TM7x modulates the susceptibility of its host bacteria to phage infection and promotes their coexistence.

Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long-term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships with their host bacteria and impact their physiology. Here, we showed that during surface-associated growth, a human oral Saccharibacteria isolate (named TM7x) protects its host bacterium, a Schaalia odontolytica strain (named XH001) against lytic phage LC001 predation. RNA-Sequencing analysis identified in XH001 a gene cluster with predicted functions involved in the biogenesis of cell wall polysaccharides (CWP), whose expression is significantly down-regulated when forming a symbiosis with TM7x. Through genetic work, we experimentally demonstrated the impact of the expression of this CWP gene cluster on bacterial-phage interaction by affecting phage binding. In vitro coevolution experiments further showed that the heterogeneous populations of TM7x-associated and TM7x-free XH001, which display differential susceptibility to LC001 predation, promote bacteria and phage coexistence. Our study highlights the tripartite interaction between the bacterium, episymbiont, and phage. More importantly, we present a mechanism, i.e., episymbiont-mediated modulation of gene expression in host bacteria, which impacts their susceptibility to phage predation and contributes to the formation of "source-sink" dynamics between phage and bacteria in biofilm, promoting their long-term coexistence within the human microbiome.

Huangbaiye Tuji combined with Longdan Xiegan Decoction for anal cryptitis: Analysis of clinical efficacy and its influence on disease recurrence.

Given the rising incidence of anal cryptitis (AC) in recent years, it is of great significance to find an effective and safe treatment scheme to ensure the healthy life of patients. In this study, we explored the clinical efficacy of Huangbaiye Tuji combined with Longdan Xiegan Decoction (LDXGD) for AC and observed changes in patients' cellular immune function, which can provide a new reference for future treatment of AC. By comparison, we found that compared with Huangbaiye Tuji treatment alone, its combination with LDXGD had better clinical efficacy and high safety, contributing to more significant relief of inflammatory reaction and oxidative stress. In terms of immune function, the patients' humoral and cellular immunity were more effectively enhanced after the combination therapy. According to these results, it is recommended to use Huangbaiye Tuji combined with LDXGD in the treatment of AC.

A novel method for quantitative determination of multiple substances using Raman spectroscopy combined with CWT.

The identification of mixed solutions is a challenging and important subject in chemical analysis. In this paper, we propose a novel workflow that enables rapid qualitative and quantitative detection of mixed solutions. We use a methanol-ethanol mixed solution as an example to demonstrate the superiority of this workflow. The workflow includes the following steps: (1) converting Raman spectra into Raman images through CWT; (2) using MobileNetV3 as the backbone network, improved multi-label and multi-channel synchronization enables simultaneous prediction of multiple mixture concentrations; and (3) using transfer learning and multi-stage training strategies for training to achieve accurate quantitative analysis. We compare six traditional machine learning algorithms and two deep learning models to evaluate the performance of our new method. The experimental results show that our model has achieved good prediction results when predicting the concentration of methanol and ethanol, and the coefficient of determination R2 is greater than 0.999. At different concentrations, both MAPE and RSD outperform other models, which demonstrates that our workflow has outstanding analytical capabilities. Importantly, we have solved the problem that current quantitative analysis algorithms for Raman spectroscopy are almost unable to accurately predict the concentration of multiple substances simultaneously. In conclusion, it is foreseeable that this non-destructive, automated, and highly accurate workflow can further advance Raman spectroscopy.

Bacteriophage protein Dap1 regulates evasion of antiphage immunity and Pseudomonas aeruginosa virulence impacting phage therapy in mice.

Bacteriophages have evolved diverse strategies to overcome host defence mechanisms and to redirect host metabolism to ensure successful propagation. Here we identify a phage protein named Dap1 from Pseudomonas aeruginosa phage PaoP5 that both modulates bacterial host behaviour and contributes to phage fitness. We show that expression of Dap1 in P. aeruginosa reduces bacterial motility and promotes biofilm formation through interference with DipA, a c-di-GMP phosphodiesterase, which causes an increase in c-di-GMP levels that trigger phenotypic changes. Results also show that deletion of dap1 in PaoP5 significantly reduces genome packaging. In this case, Dap1 directly binds to phage HNH endonuclease, prohibiting host Lon-mediated HNH degradation and promoting phage genome packaging. Moreover, PaoP5Δdap1 fails to rescue P. aeruginosa-infected mice, implying the significance of dap1 in phage therapy. Overall, these results highlight remarkable dual functionality in a phage protein, enabling the modulation of host behaviours and ensuring phage fitness.