Distinct Long- and Short-Term Adaptive Mechanisms in Pseudomonas aeruginosa.

Heterogeneous environments such as the chronically infected cystic fibrosis lung drive the diversification of Pseudomonas aeruginosa populations into, e.g., mucoid, alginate-overproducing isolates or small-colony variants (SCVs).

Predicting Influenza A Virus Infection in the Lung from Hematological Data with Machine Learning.

The tracking of pathogen burden and host responses with minimally invasive methods during respiratory infections is central for monitoring disease development and guiding treatment decisions. Utilizing a standardized murine model of respiratory influenza A virus (IAV) infection, we developed and tested different supervised machine learning models to predict viral burden and immune response markers, i.e.

Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation.

The peptidyl-prolyl--isomerase (PPIase) macrophage infectivity potentiator (Mip) contributes to the pathogenicity and fitness of L. pneumophila, the causative agent of Legionnaires' disease. Here, we identified the stringent starvation protein SspB, hypothetical protein Lpc2061, and flagellin FlaA as bacterial interaction partners of Mip.

A Photoconvertible Reporter System for Bacterial Metabolic Activity Reveals That Staphylococcus aureus Enters a Dormant-Like State to Persist within Macrophages.

Staphylococcus aureus is a leading cause of difficult-to-treat infections. The capacity of S. aureus to survive and persist within phagocytic cells is an important factor contributing to therapy failures and infection recurrence.

Clostridioides difficile Modifies its Aromatic Compound Metabolism in Response to Amidochelocardin-Induced Membrane Stress.

Amidochelocardin is a broad-spectrum antibiotic with activity against many Gram-positive and Gram-negative bacteria. According to recent data, the antibiotic effect of this atypical tetracycline is directed against the cytoplasmic membrane, which is associated with the dissipation of the membrane potential. Here, we investigated the effect of amidochelocardin on the proteome of Clostridioides difficile to gain insight into the membrane stress physiology of this important anaerobic pathogen.

The Sixth Element: a 102-kb RepABC Plasmid of Xenologous Origin Modulates Chromosomal Gene Expression in Dinoroseobacter shibae.

The model organism Dinoroseobacter shibae and many other marine (, ) are characterized by a multipartite genome organization. Here, we show that the original isolate (Dshi-6) contained six extrachromosomal replicons (ECRs), whereas the strain deposited at the DSMZ (Dshi-5) lacked a 102-kb plasmid. To determine the role of the sixth plasmid, we investigated the genomic and physiological differences between the two strains.

A So-Far Overlooked Secondary Conformation State in the Binding Mode of SARS-CoV-2 Spike Protein to Human ACE2 and Its Conversion Rate Are Crucial for Estimating Infectivity Efficacy of the Underlying Virus Variant.

Since its outbreak in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread with high transmission efficiency across the world, putting health care as well as economic systems under pressure. During the course of the pandemic, the originally identified SARS-CoV-2 variant has been multiple times replaced by various mutant versions, which showed enhanced fitness due to increased infection and transmission rates. In order to find an explanation for why SARS-CoV-2 and its emerging mutated versions showed enhanced transmission efficiency compared with SARS-CoV (2002), an enhanced binding affinity of the spike protein to human angiotensin converting enzyme 2 (hACE2) has been proposed by crystal structure analysis and was identified in cell culture models.

Identification of Antimotilins, Novel Inhibitors of Helicobacter pylori Flagellar Motility That Inhibit Stomach Colonization in a Mouse Model.

New treatment options against the widespread cancerogenic gastric pathogen Helicobacter pylori are urgently needed. We describe a novel screening procedure for inhibitors of H. pylori flagellar biosynthesis.

Dual Effect: High NADH Levels Contribute to Efflux-Mediated Antibiotic Resistance but Drive Lethality Mediated by Reactive Oxygen Species.

In light of the antibiotic crisis, emerging strategies to sensitize bacteria to available antibiotics should be explored. Several studies on the mechanisms of killing suggest that bactericidal antibiotic activity is enforced through the generation of reactive oxygen species (ROS-lethality hypothesis). Here, we artificially manipulated the redox homeostasis of the model opportunistic pathogen Pseudomonas aeruginosa using specific enzymes that catalyze either the formation or oxidation of NADH.

Rapid SARS-CoV-2 Adaptation to Available Cellular Proteases.

Recent emergence of SARS-CoV-1 variants demonstrates the potential of this virus for targeted evolution, despite its overall genomic stability. Here we show the dynamics and the mechanisms behind the rapid adaptation of SARS-CoV-2 to growth in Vero E6 cells. The selective advantage for growth in Vero E6 cells is due to increased cleavage efficiency by cathepsins at the mutated S1/S2 site.

Influenza A Virus (H1N1) Infection Induces Microglial Activation and Temporal Dysbalance in Glutamatergic Synaptic Transmission.

Influenza A virus (IAV) causes respiratory tract disease and is responsible for seasonal and reoccurring epidemics affecting all age groups. Next to typical disease symptoms, such as fever and fatigue, IAV infection has been associated with behavioral alterations presumably contributing to the development of major depression. Previous experiments using IAV/H1N1 infection models have shown impaired hippocampal neuronal morphology and cognitive abilities, but the underlying pathways have not been fully described.

Higher Trimethylamine--Oxide Plasma Levels with Increasing Age Are Mediated by Diet and Trimethylamine-Forming Bacteria.

The gut microbiota-dependent metabolite trimethylamine--oxide (TMAO) is linked to an increased risk for cardiovascular diseases. Trimethylamine (TMA), which is subsequently oxidized to TMAO in the liver, is formed by intestinal bacteria via distinct biochemical routes from dietary precursors that are enriched in animal product-based foods. To get a full picture of the entire process of the diet > gut microbiota > TMAO axis, we quantified potential TMA-forming gut bacteria and plasma metabolites using gene-targeted assays and targeted metabolomics on a subsample ( = 425) of a German population-based cohort study.

Targeting Bacterial Gyrase with Cystobactamid, Fluoroquinolone, and Aminocoumarin Antibiotics Induces Distinct Molecular Signatures in Pseudomonas aeruginosa.

The design of novel antibiotics relies on a profound understanding of their mechanism of action. While it has been shown that cellular effects of antibiotics cluster according to their molecular targets, we investigated whether compounds binding to different sites of the same target can be differentiated by their transcriptome or metabolome signatures. The effects of three fluoroquinolones, two aminocoumarins, and two cystobactamids, all inhibiting bacterial gyrase, on Pseudomonas aeruginosa at subinhibitory concentrations could be distinguished clearly by RNA sequencing as well as metabolomics.