Oral co-administration of Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 improves host defense against influenza A virus infection.

Influenza is an important zoonotic disease that persistently threatens global public health. While it is widely acknowledged that probiotics can modulate the host response to protect the host against infectious disease, the prophylactic efficacy on respiratory viral infection and the detailed mechanism remains elusive. Lactobacillus, the most commonly used probiotic widely applied in food production, has garnered significant attention. In our study utilizing both C57BL/6 and BALB/c mouse models, we explored the protective effect against two strains of influenza virus, A/Mink/China/01/2014(H9N2) and A/California/04/2009(H1N1), through the administration of Lactiplantibacillus plantarum strain 16 (L. plantarum 16) and Lacticaseibacillus rhamnosus strain P118 (L. rhamnosus P118), aiming to identify robust probiotic strains with antiviral properties. Our findings indicate that administering L. plantarum 16 or L. rhamnosus P118 alone does not provide sufficient protection against influenza. However, the co-administration of L. plantarum 16 and L. rhamnosus P118 dramatically reduces viral titers in the respiratory tract and lung, thereby markedly alleviating the clinical symptoms, improving prognosis, and reducing mortality. The mechanisms underlying this effect involve the modulation of host gut microbiota and metabolism through the co-administration of L. plantarum 16 and L. rhamnosus P118, resulting in enrichment of Firmicutes and enhancement of phenylalanine-related metabolism, ultimately leading to an augmentation of the antiviral immune response. Notably, we identified that the circulating metabolic molecule 2-Hydroxycinnamic acid plays a significant role in combating influenza. Our data suggest the potential utility of L. plantarum 16 and L. rhamnosus P118 two-bacterium or 2-Hydroxycinnamic acid in preventing influenza.IMPORTANCEVaccination represents the most optimal strategy to control influenza. Nevertheless, influenza viruses constantly evolve due to antigenic drift and shift, leading to the need for regular updates on influenza vaccines. Additionally, vaccination failure poses significant challenges to influenza prevention. Therefore, it is essential and beneficial to identify novel or universal antiviral measures to protect against influenza. While cumulative data suggest that probiotics offer protection against infectious diseases, the specific mechanisms, such as the effective metabolites or components, remain largely unknown. Our research discovered the capacity of combinational two-bacterium Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 to fight against influenza infection in a mouse model. The protection may occur through modulating the host's gut microbiota and metabolism, further influencing the host's antiviral immune response. Notably, we have identified a novel metabolic molecule, 2-Hydroxycinnamic acid, capable of enhancing antiviral response and restricting viral replication in vivo.

Polymyalgia rheumatica and giant cell arteritis: A bidirectional Mendelian randomization study.

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) as 2 types of autoimmune diseases are frequently concomitant, and Mendelian randomization (MR) was applied in this study to assess the causal relationship between them. In this study, single-nucleotide polymorphism (SNP) was used as the instrumental variable for Mendelian analysis, and the SNP data of GCA and PMR were obtained from the FinnGen Biobank databases. SNPs are significantly correlated with GCA and PMR and were screened based on preset thresholds. Inverse variance weighted analysis was used as the main analysis, supplemented with MR-Egger and weighted median. The evidence of the impact of GCA on PMR risk was found in inverse variance weighted results (odds ratio, 1.22 [95% confidence interval, 1.11-1.34]; P < .01), and the evidence of the impact of PMR on GCA risk has also been found (odds ratio, 1.58 [95% confidence interval, 1.28-1.96]; P < .01). Finally, the stability and reliability of the results were tested using the retention method, heterogeneity test, and horizontal gene pleiotropy test. MR analysis indicates that GCA increases the risk of PMR and PMR is an important risk factor for GCA, with a causal relationship. The potential value of reasonable management of PMR in patients with GCA has received high attention. In addition, novel GCA therapeutics may be indicated for PMR, and it is a potential for further investigation.

In vivo detection of endogenous toxic phenolic compounds of intestine.

Phenol and p-cresol are two common toxic small molecules related to various diseases. Existing reports confirmed that high L-tyrosine in the daily diet can increase the concentration of phenolic compounds in blood and urine. L-tyrosine is a common component of protein-rich foods. Some anaerobic bacteria in the gut can convert non-toxic l-tyrosine into these two toxic phenolic compounds, phenol and p-cresol. Existing methods have been constructed for measuring the concentration of phenolic compound in feces. However, there is still a lack of direct visual evidence to measure the phenolic compounds in the intestine. In this study, we aimed to construct a whole-cell biosensor for phenolic compounds detection based on the dmpR, the regulator from the phenol metabolism cluster. The commensal bacterium Citrobacter amalonaticus PS01 was selected and used as the chassis. Compared with the biosensor based on ECN1917, the biosensor PS01[dmpR] could better implant into the mouse gut through gavage and showed a higher sensitive to phenolic compound. And the concentration of phenolic compounds in the intestines could be observed with the help of in vivo imaging system using PS01[dmpR]. This paper demonstrated endogenous phenol synthesis in the gut and the strategy of using commensal bacteria to construct whole-cell biosensors for detecting small molecule compounds in the intestines.

A detailed analysis of 16S rRNA gene sequencing and conventional PCR-based testing for the diagnosis of bacterial pathogens and discovery of novel bacteria.

This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.

Minimally invasive palliative treatment of malignant tracheoesophageal fistula using cardiac septal occluder.

INTRODUCTION: Tracheoesophageal fistula (TEF) especially malignant TEF (mTEF) is an uncommon yet critical medical condition necessitating immediate intervention. This life-threatening condition frequently manifests in critically ill patients who are dependent on prolonged mechanical ventilation and are unsuitable candidates for thoracotomy due to their compromised health status. The Management of these mTEF patients remain a significant challenge.This study aimed to evaluate the safety and efficacy of using a cardiac septal occluder for the closure of mTEF. METHODS: 8 patients with mTEF underwent closure surgery using atrial/ventricular septal defect (ASD/VSD) septal occluders at the Respiratory Department of HuBei Yichang Central People's Hospital from 2021 to 2023. The procedure involved percutaneous placement of the occluder through the fistula to achieve closure. RESULTS: The placement of the cardiac septal occluder was successfully achieved with ease and efficiency in all patients. The study demonstrated that the use of cardiac septal occluder therapy in patients with mTEF can alleviate symptoms, improve quality of life, and enhance survival rates, with no significant complications observed. Furthermore, the study provided comprehensive details on surgical indications, preoperative evaluation and diagnosis, selection of occluder, methods of occlusion, and postoperative care. CONCLUSIONS: The application of cardiac septal occluder in the treatment of mTEF is a safe and effective palliative treatment. This approach may be particularly beneficial for patients with a high risk of complications and mortality associated with traditional surgical interventions.

Biomimetic and Wound Microenvironment-Modulating PEGylated Glycopolypeptide Hydrogels for Arterial Massive Hemorrhage and Wound Prohealing.

Despite great progress in the hydrogel hemostats and dressings, they generally lack resistant vascular bursting pressure and intrinsic bioactivity to meet arterial massive hemorrhage and proheal wounds. To address the problems, we design a kind of biomimetic and wound microenvironment-modulating PEGylated glycopolypeptide hydrogels that can be easily injected and gelled in ∼10 s. Those glycopolypeptide hydrogels have suitable tissue adhesion of ∼20 kPa, high resistant bursting pressure of ∼150 mmHg, large microporosity of ∼15 µm, and excellent biocompatibility with ∼1% hemolysis ratio and negligible inflammation. They performed better hemostasis in rat liver and rat and rabbit femoral artery bleeding models than Fibrin glue, Gauze, and other hydrogels, achieving fast arterial hemostasis of <20 s and lower blood loss of 5-13%. As confirmed by in vivo wound healing, immunofluorescent imaging, and immunohistochemical and histological analyses, the mannose-modified hydrogels could highly boost the polarization of anti-inflammatory M2 phenotype and downregulate pro-inflammatory tumor necrosis factor-α to relieve inflammation, achieving complete full-thickness healing with thick dermis, dense hair follicles, and 90% collagen deposition. Importantly, this study provides a versatile strategy to construct biomimetic glycopolypeptide hydrogels that can not only resist vascular bursting pressure for arterial massive hemorrhage but also modulate inflammatory microenvironment for wound prohealing.

Genomic investigation and nationwide tracking of pediatric invasive nontyphoidal Salmonella in China.

Invasive nontyphoidal Salmonella (iNTS) causes significant concern with ~15% morbidity, affecting populations mainly in African countries. However, iNTS infections among the Chinese pediatric population remain largely unknown. Here, we conducted a genomic investigation to study pediatric iNTS infections in a Chinese hospital. iNTS isolates accounted for 15.2% (18/119) of all nontyphoidal Salmonella (NTS) strains. Compared to non-iNTS isolates, iNTS isolates harbored a lower prevalence of antimicrobial-resistant genes of fluoroquinolones and ß-lactams, as well as disinfectant determinants and plasmids, but carried a significantly higher prevalence of cdtB, faeCDE, and tcpC genes. Importantly, we detected an emerging serovar Goldcoast as the predominant iNTS serovar locally. By integrating 320 global Goldcoast genomes based on the One Health samplings, we conducted nationwide phylogenomic tracking and detected repeated human-to-human transmission events among iNTS cases caused by an underestimated serovar Goldcoast. Together, our exploratory genomic approach highlights a new trend in pediatric iNTS infections.

Discovery of Novel Ortho-Aminophenol Derivatives Targeting Lipid Peroxidation with Potent Antiferroptotic Activities.

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.

Unified Model for Children's Brain Image Segmentation with Co-Registration Framework Guided by Longitudinal MRI.

Accurate segmentation of brain structures is crucial for analyzing longitudinal changes in children's brains. However, existing methods are mostly based on models established at a single time-point due to difficulty in obtaining annotated data and dynamic variation of tissue intensity. The main problem with such approaches is that, when conducting longitudinal analysis, images from different time points are segmented by different models, leading to significant variation in estimating development trends. In this paper, we propose a novel unified model with co-registration framework to segment children's brain images covering neonates to preschoolers, which is formulated as two stages. First, to overcome the shortage of annotated data, we propose building gold-standard segmentation with co-registration framework guided by longitudinal data. Second, we construct a unified segmentation model tailored to brain images at 0-6 years old through the introduction of a convolutional network (named SE-VB-Net), which combines our previously proposed VB-Net with Squeeze-and-Excitation (SE) block. Moreover, different from existing methods that only require both T1- and T2-weighted MR images as inputs, our designed model also allows a single T1-weighted MR image as input. The proposed method is evaluated on the main dataset (320 longitudinal subjects with average 2 time-points) and two external datasets (10 cases with 6-month-old and 40 cases with 20-45 weeks, respectively). Results demonstrate that our proposed method achieves a high performance (>92%), even over a single time-point. This means that it is suitable for brain image analysis with large appearance variation, and largely broadens the application scenarios.

Role of C/EBP Homologous Protein in Vascular Stenosis After Carotid Artery Injury.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

Salmonellosis outbreak archive in China: data collection and assembly.

Infectious disease outbreaks transcend the medical and public health realms, triggering widespread panic and impeding socio-economic development. Considering that self-limiting diarrhoea of sporadic cases is usually underreported, the Salmonella outbreak (SO) study offers a unique opportunity for source tracing, spatiotemporal correlation, and outbreak prediction. To summarize the pattern of SO and estimate observational epidemiological indicators, 1,134 qualitative reports screened from 1949 to 2023 were included in the systematic review dataset, which contained a 506-study meta-analysis dataset. In addition to the dataset comprising over 50 columns with a total of 46,494 entries eligible for inclusion in systematic reviews or input into prediction models, we also provide initial literature collection datasets and datasets containing socio-economic and climate information for relevant regions. This study has a broad impact on advancing knowledge regarding epidemic trends and prevention priorities in diverse salmonellosis outbreaks and guiding rational policy-making or predictive modeling to mitigate the infringement upon the right to life imposed by significant epidemics.

Microbiological hazards in infant and toddler food in China: A comprehensive study between 2004 and 2022.

Infant and toddler food (ITF), including powdered infant and follow-up formula (PIFF) and complementary food (CF), provides the majority of early-life nutrients for young children. As infants and toddlers are more vulnerable to foodborne diseases, the safety concern of ITF is the ultimate priority. However, nationwide surveillance for the presence of hazards, specifically microbiological hazards, in the Chinese ITF is partially known, posing a significant knowledge gap for risk ranking. Most importantly, the related regional surveys were largely published in Chinese, making the data unavailable for global sharing. To bridge these gaps, we screened 5,306 publications and conducted a comprehensive meta-analysis for microbiological hazards using 129 qualified studies. The four most reported microbiological hazards in ITF were Bacillus cereus (13.4 %), Cronobacter (4.8 %), Staphylococcus aureus (1.3 %), and Salmonella (1.1 %). B. cereus is a risk factor in ITF, specifically in PIFF, cereals, and ready-to-eat food. The prevalence of B. cereus was high in Northern and Southern China, while the prevalence of Cronobacter was high in Central China. Cronobacter is a microbiological hazard, specifically in PIFF, with a prevalence of 3.0 %. Interestingly, the prevalence dynamics of Cronobacter and B. cereus in ITF were rising and stable, respectively, whereas the prevalence of S. aureus and Salmonella decreased over time. Together, our analysis will promote the global sharing of these critical findings and may guide future policy making.

Fast and sensitive differential diagnosis of pseudorabies virus-infected versus pseudorabies virus-vaccinated swine using CRISPR-Cas12a.

IMPORTANCE: Pseudorabies virus (PRV) causes high mortality and miscarriage rates in the infected swine, and the eradication policy coupled with large-scale vaccination of live attenuated vaccines has been adopted globally against PRV. Differential diagnosis of the vaccinated and infected swine is highly demanded. Our multienzyme isothermal rapid amplification (MIRA)-Cas12a detection method described in this study can diagnose PRV with a superior sensitivity comparable to the quantitative PCR (qPCR) and a competitive detection speed (only half the time as qPCR needs). The portable feature and the simple procedure of MIRA-Cas12a make it easier to deploy for clinical diagnosis, even in resource-limited settings. The MIRA-Cas12a method would provide immediate and accurate diagnostic information for policymakers to respond promptly.

Beam-wise dose composition learning for head and neck cancer dose prediction in radiotherapy.

Automatic and accurate dose distribution prediction plays an important role in radiotherapy plan. Although previous methods can provide promising performance, most methods did not consider beam-shaped radiation of treatment delivery in clinical practice. This leads to inaccurate prediction, especially on beam paths. To solve this problem, we propose a beam-wise dose composition learning (BDCL) method for dose prediction in the context of head and neck (H&N) radiotherapy plan. Specifically, a global dose network is first utilized to predict coarse dose values in the whole-image space. Then, we propose to generate individual beam masks to decompose the coarse dose distribution into multiple field doses, called beam voters, which are further refined by a subsequent beam dose network and reassembled to form the final dose distribution. In particular, we design an overlap consistency module to keep the similarity of high-level features in overlapping regions between different beam voters. To make the predicted dose distribution more consistent with the real radiotherapy plan, we also propose a dose-volume histogram (DVH) calibration process to facilitate feature learning in some clinically concerned regions. We further apply an edge enhancement procedure to enhance the learning of the extracted feature from the dose falloff regions. Experimental results on a public H&N cancer dataset from the AAPM OpenKBP challenge show that our method achieves superior performance over other state-of-the-art approaches by significant margins. Source code is released at https://github.com/TL9792/BDCLDosePrediction.

Interphylum dissemination of NDM-5-positive plasmids in hospital wastewater from Fuzhou, China: a single-centre, culture-independent, plasmid transmission study.

BACKGROUND: The global spread of plasmid-borne carbapenem resistance is an ongoing public health challenge; however, the nature of such horizontal gene transfer events among complex bacterial communities remains poorly understood. We examined the in-situ transfer of the globally dominant New Delhi metallo-ß-lactamase (NDM)-5-positive IncX3 plasmid (denoted pX3_NDM-5) in hospital wastewater to simulate a real-world, One Health antimicrobial resistance context. METHODS: For this transmission study, we tagged pX3_NDM-5 with the green fluorescent protein gene, gfp, using a CRISPR-based method and transferred the plasmid to a donor Escherichia coli strain. Bacteria were extracted from a hospital wastewater treatment plant (Fujian Provincial Maternity and Children's Hospital, Fuzhou, China) as the bacterial recipient community. We mixed this recipient community with the E coli donor strain carrying the gfp-tagged plasmid, both with and without sodium hypochlorite (NaClO) as an environmental stressor, and conducted several culture-based and culture-independent conjugation assays. The conjugation events were observed microscopically and quantified by fluorescence-activated cell sorting. We analysed the taxonomic composition of the sorted transconjugal pool by 16S rRNA gene amplicon sequencing and assessed the stability of the plasmid in the isolated transconjugants and its ability to transfer back to E coli. FINDINGS: We show that the plasmid pX3_NDM-5 has a broad host range and can transfer across various bacterial phyla, including between Gram-negative and Gram-positive bacteria. Although environmental stress with NaClO did not affect the overall plasmid transfer frequency, it reduced the breadth of the transconjugant pool. The taxonomic composition of the transconjugal pool was distinct from that of the recipient communities, and environmental stress modulated the permissiveness of some operational taxonomic units towards the acquisition of pX3_NDM-5. Notably, pX3_NDM-5 transconjugants included the Gram-positive pathogen Enterococcus faecalis, and the plasmid could subsequently be reconjugated back to E coli. These findings suggest that E faecalis could act as a natural shuttle vector for the wide dissemination of pX3_NDM-5 plasmids. INTERPRETATION: Our culture-independent conjugation model simulates natural environmental conditions and challenges the established theory that Gram-negative and Gram-positive bacteria rarely exchange clinically important plasmids. The data show that plasmids disseminate more widely across genera and phyla than previously thought. These findings have substantial implications when considering the spread of antimicrobial resistance across One Health sectors. FUNDING: The Laboratory of Lingnan Modern Agriculture Project, the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province of China, and the Outstanding Young Research Talents Program of Fujian Agriculture and Forestry University.

Glutamate secretion by embryonic stem cells as an autocrine signal to promote proliferation.

Glutamate, the major excitatory neurotransmitter in the central nervous system, has also been found to play a role in embryonic stem (ES) cells. However, the exact mechanism and function of glutamatergic signaling in ES cells remain poorly understood. In this study, we identified a glutamatergic transmission circuit in ES cells that operates through an autocrine mechanism and regulates cell proliferation. We performed biological analyses to identify the key components involved in glutamate biosynthesis, packaging for secretion, reaction, and reuptake in ES cells, including glutaminase, vesicular glutamate transporter, glutamate N-methyl-D-aspartate (NMDA) receptor, and cell membrane excitatory amino-acid transporter (EAAT). We directly quantified the released glutamate signal using microdialysis-high performance liquid chromatography-tandem mass spectrometry (MD-HPLC-MS-MS). Pharmacological inhibition of endogenous glutamate release and the resulting tonic activation of NMDA receptors significantly affected ES cell proliferation, suggesting that ES cells establish a glutamatergic autocrine niche via releasing and responding to the transmitter for their own regulation.

Genome degradation promotes Salmonella pathoadaptation by remodeling fimbriae-mediated proinflammatory response.

Understanding changes in pathogen behavior (e.g. increased virulence, a shift in transmission channel) is critical for the public health management of emerging infectious diseases. Genome degradation via gene depletion or inactivation is recognized as a pathoadaptive feature of the pathogen evolving with the host. However, little is known about the exact role of genome degradation in affecting pathogenic behavior, and the underlying molecular detail has yet to be examined. Using large-scale global avian-restricted Salmonella genomes spanning more than a century, we projected the genetic diversity of Salmonella Pullorum (bvSP) by showing increasingly antimicrobial-resistant ST92 prevalent in Chinese flocks. The phylogenomic analysis identified three lineages in bvSP, with an enhancement of virulence in the two recently emerged lineages (L2/L3), as evidenced in chicken and embryo infection assays. Notably, the ancestor L1 lineage resembles the Salmonella serovars with higher metabolic flexibilities and more robust environmental tolerance, indicating stepwise evolutionary trajectories towards avian-restricted lineages. Pan-genome analysis pinpointed fimbrial degradation from a virulent lineage. The later engineered fim-deletion mutant, and all other five fimbrial systems, revealed behavior switching that restricted horizontal fecal-oral transmission but boosted virulence in chicks. By depleting fimbrial appendages, bvSP established persistent replication with less proinflammation in chick macrophages and adopted vertical transovarial transmission, accompanied by ever-increasing intensification in the poultry industry. Together, we uncovered a previously unseen paradigm for remodeling bacterial surface appendages that supplements virulence-enhanced evolution with increased vertical transmission.

An integrated nationwide genomics study reveals transmission modes of typhoid fever in China.

IMPORTANCE: Typhoid fever is a life-threatening disease caused by Salmonella enterica serovar Typhi, resulting in a significant disease burden across developing countries. Historically, China was very much close to the global epicenter of typhoid, but the role of typhoid transmission within China and among epicenter remains overlooked in previous investigations. By using newly produced genomics on a national scale, we clarify the complex local and global transmission history of such a notorious disease agent in China spanning the most recent five decades, which largely undermines the global public health network.

Mobilome-driven partitions of the resistome in Salmonella.

IMPORTANCE: Antimicrobial resistance (AMR) has become a significant global challenge, with an estimated 10 million deaths annually by 2050. The emergence of AMR is mainly attributed to mobile genetic elements (MGEs or mobilomes), which accelerate wide dissemination among pathogens. The interaction between mobilomes and AMR genes (or resistomes) in Salmonella, a primary cause of diarrheal diseases that results in over 90 million cases annually, remains poorly understood. The available fragmented or incomplete genomes remain a significant limitation in investigating the relationship between AMR and MGEs. Here, we collected the most extensive closed Salmonella genomes (n = 1,817) from various sources across 58 countries. Notably, our results demonstrate that resistome transmission between Salmonella lineages follows a specific pattern of MGEs and is influenced by external drivers, including certain socioeconomic factors. Therefore, targeted interventions are urgently needed to mitigate the catastrophic consequences of Salmonella AMR.