In Vivo Nitrosative Stress-Induced Expression of a Photolyase Promotes Vibrio cholerae Environmental Blue Light Resistance.

Bacterial pathogens possess a remarkable capacity to sense and adapt to ever-changing environments. For example, Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, thrives in aquatic ecosystems and human hosts through dynamic survival strategies. In this study, we investigated the role of three photolyases, enzymes that repair DNA damage caused by exposure to UV radiation and blue light, in the environmental survival of V.

Tectorigenin Reduces Dabie bandavirus-Induced Cytokine Storm by Regulating Toll-Like Receptor 7/Extracellular Signal-Regulated Kinase Pathway.

Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging infectious disease caused by Dabie bandavirus (DBV). Tectorigenin has been demonstrated to exert anti-inflammatory effect. Here, we aimed to investigate the effects of tectorigenin on DBV-induced cytokine storm.

Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis.

Background: Cryptococcosis is progressively acknowledged among people, irrespective of the human with or without immunodeficiency virus (HIV). This change in epidemiology has been recorded in recent years, prompting closer examination and a broader understanding of the disease manifestations and risk factors.

Methods: The data of cryptococcal infections in China during 11 years were retrospectively analyzed.

Early predictors of Epstein-Barr virus infection in patients with severe fever with thrombocytopenia syndrome.

Background: Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients.

Methods: In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups.

Case report: tracheobronchial diverticulum, a potential risk for diving?

Tracheobronchial diverticulum (TBD) is an asymptomatic, benign cystic lesion outside the lumen of the trachea and bronchus. This is the first report case of a SCUBA (self contained underwater breathing apparatus) diver diagnosed with TBD, which is a potential risk to diving. No literature or guideline is available so far on the diving fitness for patients with congenital or acquired TBD condition.

The dose-response relationship between smoking and the risk factor for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome.

Objectives: Invasive pulmonary aspergillosis (IPA) is common in immuno-compromised people, and a high incidence of IPA has been found in patients with severe fever with thrombocytopenia syndrome (SFTS). Our study aimed to determine the independent risk factors for IPA and the relationship between smoking status and the risk of IPA in SFTS patients.

Methods: A retrospective analysis of SFTS patients in the First Affiliated Hospital of Nanjing Medical University from May 2011 to December 2021 was reviewed.

An Intestinal Bacillus velezensis Isolate Displays Broad-Spectrum Antibacterial Activity and Prevents Infection of Both Gram-Positive and Gram-Negative Pathogens .

The increasing prevalence of drug-resistant bacteria has significantly diminished the effectiveness of antibiotics in clinical settings, leading to the emergence of untreatable bacterial infections. To address this public health challenge, the gut microbiome represents a promising source of novel antimicrobial therapeutics. In this study, we screened mouse intestinal isolates for growth inhibitory activity against the human enteric pathogen Vibrio cholerae and identified a strain of spore-forming Bacillus velezensis, named BVM7, that produced a potent antibiotic with activity against V.

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics.

Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis, burn wounds, immunodeficiency, chronic obstructive pulmonary disorder (COPD), cancer, and severe infection requiring ventilation, such as COVID-19. P.

S-Nitrosylation of the virulence regulator AphB promotes Vibrio cholerae pathogenesis.

Vibrio cholerae is the etiologic agent of the severe human diarrheal disease cholera. To colonize mammalian hosts, this pathogen must defend against host-derived toxic compounds, such as nitric oxide (NO) and NO-derived reactive nitrogen species (RNS). RNS can covalently add an NO group to a reactive cysteine thiol on target proteins, a process called protein S-nitrosylation, which may affect bacterial stress responses.

cGAS modulates cytokine secretion and bacterial burdens by altering the release of mitochondrial DNA in pseudomonas pulmonary infection.

Cyclic GMP-AMP synthase (cGAS) is essential for fighting against viruses and bacteria, but how cGAS is involved in host immune response remains largely elusive. Here, we uncover the crucial role of cGAS in host immunity based on a Pseudomonas aeruginosa pulmonary infection model. cGAS mice showed more heavy bacterial burdens and serious lung injury accompanied with exorbitant proinflammatory cytokines than wild-type mice.

A commensal-encoded genotoxin drives restriction of colonization and host gut microbiome remodeling.

SignificanceIn a polymicrobial battlefield where different species compete for nutrients and colonization niches, antimicrobial compounds are the sword and shield of commensal microbes in competition with invading pathogens and each other. The identification of an -produced genotoxin, colibactin, and its specific targeted killing of enteric pathogens and commensals, including and , sheds light on our understanding of intermicrobial interactions in the mammalian gut. Our findings elucidate the mechanisms through which genotoxins shape microbial communities and provide a platform for probing the larger role of enteric multibacterial interactions regarding infection and disease outcomes.

Type III CRISPR-based RNA editing for programmable control of SARS-CoV-2 and human coronaviruses.

Gene-editing technologies, including the widespread usage of CRISPR endonucleases, have the potential for clinical treatments of various human diseases. Due to the rapid mutations of SARS-CoV-2, specific and effective prevention and treatment by CRISPR toolkits for coronavirus disease 2019 (COVID-19) are urgently needed to control the current pandemic spread. Here, we designed Type III CRISPR endonuclease antivirals for coronaviruses (TEAR-CoV) as a therapeutic to combat SARS-CoV-2 infection.

Repurposable drugs for SARS-CoV-2 and influenza sepsis with scRNA-seq data targeting post-transcription modifications.

Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. The lack of time for new drug discovery and the urgent need for rapid disease control to reduce mortality have led to a search for quick and effective alternatives to novel therapeutics, for example drug repurposing. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.

Thiol-based functional mimicry of phosphorylation of the two-component system response regulator ArcA promotes pathogenesis in enteric pathogens.

Pathogenic bacteria can rapidly respond to stresses such as reactive oxygen species (ROS) using reversible redox-sensitive oxidation of cysteine thiol (-SH) groups in regulators. Here, we use proteomics to profile reversible ROS-induced thiol oxidation in Vibrio cholerae, the etiologic agent of cholera, and identify two modified cysteines in ArcA, a regulator of global carbon oxidation that is phosphorylated and activated under low oxygen. ROS abolishes ArcA phosphorylation but induces the formation of an intramolecular disulfide bond that promotes ArcA-ArcA interactions and sustains activity.

Microbial and genetic-based framework identifies drug targets in inflammatory bowel disease.

With increasing incidence and prevalence of inflammatory bowel disease (IBD), it has become one of the major public health threats, and there is an urgent need to develop new therapeutic agents. Although the pathogenesis of IBD is still unclear, previous research has provided evidence for complex interplays between genetic, immune, microbial, and environmental factors. Here, we constructed a gene-microbiota interaction-based framework to discover IBD biomarkers and therapeutics.

Gut Microbiota Regulate Gut-Lung Axis Inflammatory Responses by Mediating ILC2 Compartmental Migration.

Gut microbiota is increasingly linked to the development of various pulmonary diseases through a gut-lung axis. However, the mechanisms by which gut commensal microbes impact trafficking and functional transition of immune cells remain largely unknown. Using integrated microbiota dysbiosis approaches, we uncover that the gut microbiota directs the migration of group 2 innate lymphoid cells (ILC2s) from the gut to the lung through a gut-lung axis.

Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection.

Bitter receptors function primarily in sensing taste, but may also have other functions, such as detecting pathogenic organisms due to their agile response to foreign objects. The mouse taste receptor type-2 member 138 (TAS2R138) is a member of the G-protein-coupled bitter receptor family, which is not only found in the tongue and nasal cavity, but also widely distributed in other organs, such as the respiratory tract, gut, and lungs. Despite its diverse functions, the role of TAS2R138 in host defense against bacterial infection is largely unknown.

Pseudomonas aeruginosa T6SS-mediated molybdate transport contributes to bacterial competition during anaerobiosis.

Type VI secretion system (T6SS) is widely distributed in Gram-negative bacteria and functions as a versatile protein export machinery that translocates effectors into eukaryotic or prokaryotic target cells. Growing evidence indicates that T6SS can deliver several effectors to promote bacterial survival in harmful environments through metal ion acquisition. Here, we report that the Pseudomonas aeruginosa H2-T6SS mediates molybdate (MoO) acquisition by secretion of a molybdate-binding protein, ModA.

Crosstalk Between Lung and Extrapulmonary Organs in Infection and Inflammation.

Acute and chronic lung inflammation is a risk factor for various diseases involving lungs and extrapulmonary organs. Intercellular and interorgan networks, including crosstalk between lung and brain, intestine, heart, liver, and kidney, coordinate host immunity against infection, protect tissue, and maintain homeostasis. However, this interaction may be counterproductive and cause acute or chronic comorbidities due to dysregulated inflammation in the lung.

Identification of cGAS as an innate immune sensor of extracellular bacterium .

Cyclic GMP-AMP synthase (cGAS) is reported essential for detecting intracellular bacteria. However, it remains to be determined whether and how cGAS is involved in extracellular bacterial infection. Here, we report that cGAS is essential for mediating type I interferon (IFN) production in infection by multiple extracellular pathogens, including , , and In addition, the canonical cGAS-stimulator of interferon gene (STING)-IFN axis is required for protecting mice from induced mouse acute pulmonary infection, confirmed in cGAS pathway-specific gene deficiency mouse models.

Identification of Repurposable Drugs and Adverse Drug Reactions for Various Courses of COVID-19 Based on Single-Cell RNA Sequencing Data.

Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. There is no specific drug for COVID-19, highlighting the urgent need for the development of effective therapeutics. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.

Annexin A2 regulates unfolded protein response via IRE1-XBP1 axis in macrophages during P. aeruginosa infection.

Pseudomonas aeruginosa is a severe Gram-negative opportunistic bacterium that causes a spectrum of organ system diseases, particularly in immunocompromised patients. This bacterium has been shown to induce unfolded protein response (UPR) during mammalian infection. Annexin A2 (AnxA2) is a multicompartmental protein relating to a number of cellular processes; however, it remains unknown whether AnxA2 coordinates a UPR pathway under bacterial infection conditions.

Calling for a united action to defeat COVID-19.

The widespread and lingering pandemic of COVID-19 is partly due to disjointed international countermeasures and policies enforced by different countries. We have been witnessing disparity in policies and measures in different countries and regions: some are in much better control than others. To effectively deal with this and future devastating pandemics, we as human beings must work together to coordinate a concerted, cooperative international policy to reduce or possibly avoid unnecessary health crises, and life and economic losses.