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Cell Metabolism Oct 2023Pseudomonas aeruginosa is a common cause of pulmonary infection. As a Gram-negative pathogen, it can initiate a brisk and highly destructive inflammatory response;...
Pseudomonas aeruginosa is a common cause of pulmonary infection. As a Gram-negative pathogen, it can initiate a brisk and highly destructive inflammatory response; however, most hosts become tolerant to the bacterial burden, developing chronic infection. Using a murine model of pneumonia, we demonstrate that this shift from inflammation to disease tolerance is promoted by ketogenesis. In response to pulmonary infection, ketone bodies are generated in the liver and circulate to the lungs where they impose selection for P. aeruginosa strains unable to display surface lipopolysaccharide (LPS). Such keto-adapted LPS strains fail to activate glycolysis and tissue-damaging cytokines and, instead, facilitate mitochondrial catabolism of fats and oxidative phosphorylation (OXPHOS), which maintains airway homeostasis. Within the lung, P. aeruginosa exploits the host immunometabolite itaconate to further stimulate ketogenesis. This environment enables host-P. aeruginosa coexistence, supporting both pathoadaptive changes in the bacteria and the maintenance of respiratory integrity via OXPHOS.
Topics: Mice; Animals; Pseudomonas aeruginosa; Lipopolysaccharides; Lung; Inflammation; Ketone Bodies
PubMed: 37793346
DOI: 10.1016/j.cmet.2023.09.001 -
Cell Reports Jul 2023Plant response to pathogen infection varies within a leaf, yet this heterogeneity is not well resolved. We expose Arabidopsis to Pseudomonas syringae or mock treatment...
Plant response to pathogen infection varies within a leaf, yet this heterogeneity is not well resolved. We expose Arabidopsis to Pseudomonas syringae or mock treatment and profile >11,000 individual cells using single-cell RNA sequencing. Integrative analysis of cell populations from both treatments identifies distinct pathogen-responsive cell clusters exhibiting transcriptional responses ranging from immunity to susceptibility. Pseudotime analyses through pathogen infection reveals a continuum of disease progression from an immune to a susceptible state. Confocal imaging of promoter-reporter lines for transcripts enriched in immune cell clusters shows expression surrounding substomatal cavities colonized or in close proximity to bacterial colonies, suggesting that cells within immune clusters represent sites of early pathogen invasion. Susceptibility clusters exhibit more general localization and are highly induced at later stages of infection. Overall, our work shows cellular heterogeneity within an infected leaf and provides insight into plant differential response to infection at a single-cell level.
Topics: Arabidopsis; Pseudomonas syringae; Arabidopsis Proteins; Plant Leaves; Plant Diseases; Gene Expression Regulation, Plant
PubMed: 37342910
DOI: 10.1016/j.celrep.2023.112676 -
Biometals : An International Journal on... Aug 2023In the genus Pseudomonas, zinc homeostasis is mediated by a complete set of import and export systems, whose expression is precisely controlled by three transcriptional... (Review)
Review
In the genus Pseudomonas, zinc homeostasis is mediated by a complete set of import and export systems, whose expression is precisely controlled by three transcriptional regulators: Zur, CzcR and CadR. In this review, we describe in detail our current knowledge of these systems, their regulation, and the biological significance of zinc homeostasis, taking Pseudomonas aeruginosa as our paradigm. Moreover, significant parts of this overview are dedicated to highlight interactions and cross-regulations between zinc and copper import/export systems, and to shed light, through a review of the literature and comparative genomics, on differences in gene complement and function across the whole Pseudomonas genus. The impact and importance of zinc homeostasis in Pseudomonas and beyond will be discussed throughout this review.
Topics: Pseudomonas; Zinc; Homeostasis; Pseudomonas aeruginosa; Copper; Bacterial Proteins; Gene Expression Regulation, Bacterial
PubMed: 36472780
DOI: 10.1007/s10534-022-00475-5 -
Current Opinion in Chemical Biology Feb 2024Exopolysaccharides are produced and excreted by bacteria in the generation of biofilms to provide a protective environment. These polysaccharides are generally generated... (Review)
Review
Exopolysaccharides are produced and excreted by bacteria in the generation of biofilms to provide a protective environment. These polysaccharides are generally generated as heterogeneous polymers of varying length, featuring diverse substitution patterns. To obtain well-defined fragments of these polysaccharides, organic synthesis often is the method of choice, as it allows for full control over chain length and the installation of a pre-determined substitution pattern. This review presents several recent syntheses of exopolysaccharide fragments of Pseudomonas aeruginosa and Staphylococcus aureus and illustrates how these have been used to study biosynthesis enzymes and generate synthetic glycoconjugate vaccines.
Topics: Polysaccharides, Bacterial; Biofilms; Pseudomonas aeruginosa
PubMed: 38134611
DOI: 10.1016/j.cbpa.2023.102418 -
Infection and Immunity Aug 2023The ubiquitous bacterial pathogen Pseudomonas aeruginosa is responsible for severe infections in patients with burns, cystic fibrosis, and neutropenia. Biofilm formation...
The ubiquitous bacterial pathogen Pseudomonas aeruginosa is responsible for severe infections in patients with burns, cystic fibrosis, and neutropenia. Biofilm formation gives physical refuge and a protected microenvironment for sessile cells, rendering cure by antibiotics a challenge. Bacteriophages have evolved to prey on these biofilms over millions of years, using hydrolases and depolymerases to penetrate biofilms and reach cellular targets. Here, we assessed how a newly discovered KMV-like phage (ΦJB10) interacts with antibiotics to treat P. aeruginosa more effectively in both planktonic and biofilm forms. By testing representatives of four classes of antibiotics (cephalosporins, aminoglycosides, fluoroquinolones, and carbapenems), we demonstrated class-dependent interactions between ΦJB10 and antibiotics in both biofilm clearance and P. aeruginosa killing. Despite identifying antagonism between some antibiotic classes and ΦJB10 at early time points, all classes showed neutral to favorable interactions with the phage at later time points. In one notable example where the antibiotic alone had poor activity against both biofilm and high-density planktonic cells, we found that addition of ΦJB10 demonstrated synergy and resulted in effective treatment of both. Further, ΦJB10 seemed to act as an adjuvant to several antibiotics, reducing the concentration of antibiotics required to ablate the biofilm. This report shows that phages such as ΦJB10 may be valuable additions to the armamentarium against difficult-to-treat biofilm-based infections.
Topics: Humans; Anti-Bacterial Agents; Pseudomonas Phages; Pseudomonas Infections; Bacteriophages; Cephalosporins; Biofilms; Pseudomonas aeruginosa
PubMed: 37404162
DOI: 10.1128/iai.00065-23 -
Viruses Oct 2023Half a century has passed since the discovery of Pseudomonas phage phi6, the first enveloped dsRNA bacteriophage to be isolated. It remained the sole known dsRNA phage... (Review)
Review
Half a century has passed since the discovery of Pseudomonas phage phi6, the first enveloped dsRNA bacteriophage to be isolated. It remained the sole known dsRNA phage for a quarter of a century and the only recognised member of the family until the year 2018. After the initial discovery of phi6, additional dsRNA phages have been isolated from globally distant locations and identified in metatranscriptomic datasets, suggesting that this virus type is more ubiquitous in nature than previously acknowledged. Most identified dsRNA phages infect strains and utilise either pilus or lipopolysaccharide components of the host as the primary receptor. In addition to the receptor-mediated strictly lytic lifestyle, an alternative persistent infection strategy has been described for some dsRNA phages. To date, complete genome sequences of fourteen dsRNA phage isolates are available. Despite the high sequence diversity, similar sets of genes can typically be found in the genomes of dsRNA phages, suggesting shared evolutionary trajectories. This review provides a brief overview of the recognised members of the virus family and related dsRNA phage isolates, outlines the current classification of dsRNA phages, and discusses their relationships with eukaryotic RNA viruses.
Topics: Bacteriophages; Pseudomonas Phages; Pseudomonas; Genome, Viral
PubMed: 38005832
DOI: 10.3390/v15112154 -
Ugeskrift For Laeger Jan 2024We present a case report detailing therapeutic application of two lytic antipseudomonal bacteriophages to treat a chronic relapsing Pseudomonas aeruginosa infection of a...
We present a case report detailing therapeutic application of two lytic antipseudomonal bacteriophages to treat a chronic relapsing Pseudomonas aeruginosa infection of a prosthetic aortic graft. As there are currently no Danish laboratories offering phages for clinical therapy, and this case, to our knowledge represents the first applied phage therapy in Denmark, the practical and regulatory aspects of offering this treatment option in Denmark is briefly reviewed along with the clinical case.
Topics: Humans; Bacteriophages; Pseudomonas; Pseudomonas Phages; Blood Vessel Prosthesis; Pseudomonas aeruginosa
PubMed: 38305316
DOI: 10.61409/V09230617 -
Trends in Microbiology Aug 2023Bacillus and Pseudomonas ubiquitously occur in natural environments and are two of the most intensively studied bacterial genera in the soil. They are often coisolated... (Review)
Review
Bacillus and Pseudomonas ubiquitously occur in natural environments and are two of the most intensively studied bacterial genera in the soil. They are often coisolated from environmental samples, and as a result, several studies have experimentally cocultured bacilli and pseudomonads to obtain emergent properties. Even so, the general interaction between members of these genera is virtually unknown. In the past decade, data on interspecies interactions between natural isolates of Bacillus and Pseudomonas has become more detailed, and now, molecular studies permit mapping of the mechanisms behind their pairwise ecology. This review addresses the current knowledge about microbe-microbe interactions between strains of Bacillus and Pseudomonas and discusses how we can attempt to generalize the interaction on a taxonomic and molecular level.
Topics: Pseudomonas; Bacillus; Soil; Soil Microbiology; Bacteria
PubMed: 36878770
DOI: 10.1016/j.tim.2023.02.003 -
Frontiers in Cellular and Infection... 2023Bacterial keratitis (bacterial infection of the cornea) is a major cause of vision loss worldwide. Given the rapid and aggressive nature of the disease, immediate... (Review)
Review
Bacterial keratitis (bacterial infection of the cornea) is a major cause of vision loss worldwide. Given the rapid and aggressive nature of the disease, immediate broad-spectrum antibiotics are essential to adequately treat this disease. However, rising antibiotic resistance continues to accelerate, rendering many commonly used therapeutics increasingly ineffective. As such, there is a significant effort to understand the basic pathogenesis of common causative organisms implicated in keratitis in part, to fuel the development of novel therapies to treat this blinding disease. This review explores two common causes of bacterial keratitis, and , with regards to the bacterial mediators of virulence as well as novel therapies on the horizon.
Topics: Humans; Staphylococcus aureus; Pseudomonas aeruginosa; Staphylococcal Infections; Keratitis; Pseudomonas Infections; Eye Infections, Bacterial
PubMed: 37671149
DOI: 10.3389/fcimb.2023.1250257 -
Journal of Bacteriology May 2024is a significant cause of global morbidity and mortality. Although it is often regarded as an extracellular pathogen toward human cells, numerous investigations report... (Review)
Review
is a significant cause of global morbidity and mortality. Although it is often regarded as an extracellular pathogen toward human cells, numerous investigations report its ability to survive and replicate within host cells, and additional studies demonstrate specific mechanisms enabling it to adopt an intracellular lifestyle. This ability of remains less well-investigated than that of other intracellular bacteria, although it is currently gaining attention. If intracellular bacteria are not killed after entering host cells, they may instead receive protection from immune recognition and experience reduced exposure to antibiotic therapy, among additional potential advantages shared with other facultative intracellular pathogens. For this review, we compiled studies that observe intracellular across strains, cell types, and experimental systems , as well as contextualize these findings with the few studies that report similar observations . We also seek to address key findings that drove the perception that remains extracellular in order to reconcile what is currently understood about intracellular pathogenesis and highlight open questions regarding its contribution to disease.
Topics: Pseudomonas aeruginosa; Humans; Pseudomonas Infections; Animals; Host-Pathogen Interactions
PubMed: 38597609
DOI: 10.1128/jb.00109-24