Exploration of the feasibility of clinical application of phage treatment for multidrug-resistant -induced pulmonary infection.

() commonly induces refractory infection due to its multidrug-resistant nature. To date, there have been no reports on the application of phage treatment for infection. This study was conducted to explore the feasibility of phage application in treating refractory infection by collaborating with a 59-year-old male patient with a pulmonary infection of multidrug-resistant Our experiments included three domains: ) selection of the appropriate phage, ) verification of the efficacy and safety of the selected phage, ) confirmation of phage-bacteria interactions.

Choline metabolism modulates cyclic-di-GMP signaling and virulence of Pseudomonas aeruginosa in a macrophage infection model.

Background: Bacterial pathogens frequently encounter host-derived metabolites during their colonization and invasion processes, which can serve as nutrients, antimicrobial agents, or signaling molecules for the pathogens. The essential nutrient choline (Cho) is widely known to be utilized by a diverse range of bacteria and may undergo conversion into the disease-associated metabolite trimethylamine (TMA). However, the impact of choline metabolism on bacterial physiology and virulence remains largely unexplored.

A Bacterial Quorum Sensing Regulated Protease Inhibits Host Immune Responses by Cleaving Death Domains of Innate Immune Adaptors.

Innate immune adaptor proteins are critical components of the innate immune system that propagate pro-inflammatory responses from their upstream receptors, and lead to pathogen clearance from the host. Bacterial pathogens have developed strategies to survive inside host cells without triggering the innate immune surveillance in ways that are still not fully understood. Here, it is reported that Pseudomonas aeruginosa induces its quorum sensing mechanism after macrophage engulfment.

Devising novel near-infrared aggregation-induced-emission luminogen labeling for point-of-care diagnosis of Mycobacterium tuberculosis.

Detecting and appropriately diagnosing a Mycobacterium tuberculosis infection remains technologically difficult because the pathogen commonly hides in macrophages in a dormant state. Described here is novel near-infrared aggregation-induced-emission luminogen (AIEgen) labeling developed by the current authors' laboratory for point-of-care (POC) diagnosis of an M. tuberculosis infection.

Epidemiological and genomic analyses of human isolates of between 2005 and 2021 in Shenzhen, China.

() is an important food-borne zoonotic pathogen that causes swine streptococcosis, which threatens human health and brings economic loss to the swine industry. Three-quarters of human infections are caused by serotype 2. A retrospective analysis of human cases in Shenzhen, a megacity in China, with high pork consumption, between 2005 and 2021 was conducted to understand its genomic epidemiology, pathogen virulence, and drug resistance characteristics.

DNA Methyltransferase Regulates Nitric Oxide Homeostasis and Virulence in a Chronically Adapted Pseudomonas aeruginosa Strain.

Opportunistic pathogens such as Pseudomonas aeruginosa adapt their genomes rapidly during chronic infections. Understanding their epigenetic regulation may provide biomarkers for diagnosis and reveal novel regulatory mechanisms. We performed single-molecule real-time sequencing (SMRT-seq) to characterize the methylome of a chronically adapted P.

ArsR Family Regulator MSMEG_6762 Mediates the Programmed Cell Death by Regulating the Expression of HNH Nuclease in Mycobacteria.

Programmed cell death (PCD) is the result of an intracellular program and is accomplished by a regulated process in both prokaryotic and eukaryotic organisms. Here, we report a programed cell death process in , an Actinobacteria species which involves a transcription factor and a DNase of the HNH family. We found that over-expression of an ArsR family member of the transcription factor, leads to cell death.

Pseudomonas aeruginosa modulates alginate biosynthesis and type VI secretion system in two critically ill COVID-19 patients.

Background: COVID-19 pneumonia has caused huge impact on the health of infected patients and associated with high morbidity and mortality. Shift in the lung microbial ecology upon such viral infection often worsens the disease and increases host susceptibility to superinfections. Bacterial superinfection contributes to the aggravation of COVID-19 and poses a great challenge to clinical treatments.

rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure.

Background: Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance.

Persistent Bacterial Coinfection of a COVID-19 Patient Caused by a Genetically Adapted Chronic Colonizer.

is a biofilm-forming opportunistic pathogen which causes chronic infections in immunocompromised patients and leads to high mortality rate. It is identified as a common coinfecting pathogen in COVID-19 patients causing exacerbation of illness. In our hospital, is one of the top coinfecting bacteria identified among COVID-19 patients.

Von Willebrand factor protein MSMEG_3641 is involved in biofilm formation and intracellular survival.

biofilm is associated with the virulence and persistence capability. Our aim is to delineate factors involved in biofilms development. We performed transposon mutants screen and found that mutation of MSMEG_3641, a homolog of Rv1836c, can change colony morphology and biofilm.

PE31 () Attenuates Host Cell Apoptosis and Promotes Recombinant Intracellular Survival via Up-regulating GTPase Guanylate Binding Protein-1.

The comprising proline-glutamic acid (PE) subfamily proteins associate with virulence, pathogenesis, and host-immune modulations. While the functions of most of this family members are not yet explored. Here, we explore the functions of "PE only" subfamily member PE31 (Rv3477) in virulence and host-pathogen interactions.

(Rv3340) derived hydrogen sulphide conferring bacteria stress survival.

Tuberculosis, especially multidrug resistant cases, remains an enormous public health threat. (Rv3340) an enzyme involved in methionine biosynthesis was identified and characterised for antimicrobial susceptibility. We reported that the overexpression of Rv3340 in (Ms_Rv3340) produces hydrogen sulphide (HS) for its energy in harsh conditions.

The Synergistic Effect of Exogenous Glutamine and Rifampicin Against Persisters.

Persisters, stochastic dormant variants of normal bacteria cell, represent a significant portion of the survivors upon exposure to antibiotics and other environmental stresses, which contributes substantially to high level antibiotics tolerance. Glutamine is a crucial component of the nitrogen pool that is indispensable for survival upon stresses. To study whether a synergistic effect exists between glutamine and antibiotics against persisters, the efficacy of rifampicin alone or together with exogenous glutamine upon mc 155 persisters was monitored.

Mycobacterium tuberculosis toxin Rv2872 is an RNase involved in vancomycin stress response and biofilm development.

Bacterial toxin-antitoxin (TA) systems are emerging important regulators of multiple cellular physiological events and candidates for novel antibiotic targets. To explore the role of Mycobacterium tuberculosis function, unknown toxin gene Rv2872 was heterologously expressed in Mycobacterium smegmatis (MS_Rv2872). Upon induction, MS_Rv2872 phenotype differed significantly from the control, such as increased vancomycin resistance, retarded growth, cell wall, and biofilm structure.

Emerging drugs and drug targets against tuberculosis.

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, uses various tactics to resist on antibiotics and evade host immunity. To control tuberculosis, antibiotics with novel mechanisms of action are urgently needed.

MicroRNAs play big roles in modulating macrophages response toward mycobacteria infection.

Macrophages are crucial player in the defense against multiple intracellular pathogens. Mycobacterium tuberculosis, the causative agent of tuberculosis which inflicted around one third of global population, can replicate and persist within macrophages. MicroRNAs, endogenous, small noncoding RNA, can regulate the expression of macrophages genes required for appropriate signaling.

Mycobacterium tuberculosis Rv1152 is a Novel GntR Family Transcriptional Regulator Involved in Intrinsic Vancomycin Resistance and is a Potential Vancomycin Adjuvant Target.

Novel factors involved in Mycobacteria antibiotics resistance are crucial for better targets to combat the ever-increasing drug resistant strains. Mycobacterium tuberculosis Rv1152, a novel GntR family transcriptional regulator and a promising vancomycin adjuvant target, was firstly characterized in our study. Overexpression of Rv1152 in Mycobacterium smegmatis decreased bacterial susceptibility to vancomycin.

Mycobacteriophage putative GTPase-activating protein can potentiate antibiotics.

The soaring incidences of infection by antimicrobial resistant (AR) pathogens and shortage of effective antibiotics with new mechanisms of action have renewed interest in phage therapy. This scenario is exemplified by resistant tuberculosis (TB), caused by resistant Mycobacterium tuberculosis. Mycobacteriophage SWU1 A321_gp67 encodes a putative GTPase-activating protein.

Interleukin-10 Family and Tuberculosis: An Old Story Renewed.

The interleukin-10 (IL-10) family of cytokines consists of six immune mediators, namely IL-10, IL-19, IL-20, IL-22, IL-24 and IL-26. IL-10, IL-22, IL-24 and IL-26 are critical for the regulation of host defense against Mycobacterium tuberculosis infections. Specifically, IL-10 and IL-26 can suppress the antimycobacterial immunity and promote the survival of pathogen, while IL-22 and IL-24 can generate protective responses and inhibit the intracellular growth of pathogen.

l-Serine potentiates fluoroquinolone activity against Escherichia coli by enhancing endogenous reactive oxygen species production.

Background: The increase in multiple antimicrobial-resistant bacteria seriously threatens global public health. Novel effective strategies are urgently needed. l-Serine was reported as the most effective amino acid inhibitor against bacterial growth and can sensitize Escherichia coli cells to gentamicin.

The Global Reciprocal Reprogramming between Mycobacteriophage SWU1 and Mycobacterium Reveals the Molecular Strategy of Subversion and Promotion of Phage Infection.

Bacteriophages are the viruses of bacteria, which have contributed extensively to our understanding of life and modern biology. The phage-mediated bacterial growth inhibition represents immense untapped source for novel antimicrobials. Insights into the interaction between mycobacteriophage and Mycobacterium host will inform better utilizing of mycobacteriophage.

Mycobacterium Lysine ε-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level.

Bacterial persisters, usually slow-growing, non-replicating cells highly tolerant to antibiotics, play a crucial role contributing to the recalcitrance of chronic infections and treatment failure. Understanding the molecular mechanism of persister cells formation and maintenance would obviously inspire the discovery of new antibiotics. The significant upregulation of Mycobacterium tuberculosis Rv3290c, a highly conserved mycobacterial lysine ε-aminotransferase (LAT) during hypoxia persistent model, suggested a role of LAT in persistence.

The effect of Mycobacterium tuberculosis CRISPR-associated Cas2 (Rv2816c) on stress response genes expression, morphology and macrophage survival of Mycobacterium smegmatis.

Clustered regularly interspaced short palindromic repeats (CRISPR) are present in the genome of 40% bacteria and 90% archaea. CRISPR and accompanying Cas proteins constitute an adaptive immune system against disruptive mobile genetic elements. Two CRISPRs and 9 genes encoding CRISPR-associated proteins have been found in the genome of Mycobacterium tuberculosis.