Bile acids in the lower airways is associated with airway microbiota changes in chronic obstructive pulmonary disease: an observational study.

Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder with a high degree of interindividual variability. Gastrointestinal dysfunction is common in patients with COPD and has been proposed to influence the clinical progression of the disease. Using the presence of bile acid(s) (BA) in bronchoalveolar lavage (BAL) fluid as a marker of gastric aspiration, we evaluated the relationships between BAs, clinical outcomes and bacterial lung colonisation.

Comparative genomics reveals distinct diversification patterns among LysR-type transcriptional regulators in the ESKAPE pathogen .

, a harmful nosocomial pathogen associated with cystic fibrosis and burn wounds, encodes for a large number of LysR-type transcriptional regulator proteins. To understand how and why LTTR proteins evolved with such frequency and to establish whether any relationships exist within the distribution we set out to identify the patterns underpinning LTTR distribution in and to uncover cluster-based relationships within the pangenome. Comparative genomic studies revealed that in the JGI IMG database alone ~86 000 LTTRs are present across the sequenced genomes (=699).

Detection of bile acids in bronchoalveolar lavage fluid defines the inflammatory and microbial landscape of the lower airways in infants with cystic fibrosis.

Background: Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease.

Efflux, Signaling and Warfare in a Polymicrobial World.

The discovery void of antimicrobial development has occurred at a time when the world has seen a rapid emergence and spread of antimicrobial resistance, the 'perfect storm' as it has often been described. While the discovery and development of new antibiotics has continued in the research sphere, the pipeline to clinic has largely been fed by derivatives of existing classes of antibiotics, each prone to pre-existing resistance mechanisms. A novel approach to infection management has come from the ecological perspective whereby microbial networks and evolved communities already possess small molecular capabilities for pathogen control.

Uncovering the Biotechnological Importance of .

Fungi make a fundamental contribution to several biotechnological processes, including brewing, winemaking, and the production of enzymes, organic acids, alcohols, antibiotics, and pharmaceuticals. The present review explores the biotechnological importance of the filamentous yeast-like fungus , a ubiquitous species known for its use as a starter in the dairy industry. To uncover 's biotechnological role, we performed a search for related work through the scientific indexing internet services, Web of Science and Google Scholar.

Structural modification of the alkylquinoline cell-cell communication signal, HHQ, leads to benzofuranoquinolines with anti-virulence behaviour in ESKAPE pathogens.

Microbial populations have evolved intricate networks of negotiation and communication through which they can coexist in natural and host ecosystems. The nature of these systems can be complex and they are, for the most part, poorly understood at the polymicrobial level. The Pseudomonas Quinolone Signal (PQS) and its precursor 4-hydroxy-2-heptylquinoline (HHQ) are signal molecules produced by the important nosocomial pathogen .

-Alkyl-2-Quinolonopyrones Demonstrate Antimicrobial Activity against ESKAPE Pathogens Including .

Antibiotic resistance has grown significantly in the last three decades, while research and development of new antibiotic classes has languished. Therefore, new chemical frameworks for the control of microbial behavior are urgently required. This study presents a novel suite of compounds, based on a tricyclic 4-hydroxy-2-pyrano[3,2-]quinoline-2,5(6)-dione core, with significant antibiotic activity against the ESKAPE pathogens and and the "accidental pathogen" .

Developing student codesigned immersive virtual reality simulations for teaching of challenging concepts in molecular and cellular biology.

Molecular biology theory represents a critical scaffold, which underpins multiple disciplines within life sciences education. However, it is well-documented that undergraduate students can struggle to achieve deeper understanding of key concepts and/or their application. One challenging, contributory aspect is the "invisible" nature of molecular biology processes compounded by critical 3D spatial orientations of the principal components and their interactions.

Pyrones Identified as LuxR Signal Molecules in and Their Synthetic Analogues Can Alter Multicellular Phenotypic Behavior of .

Individual bacteria communicate by the release and interpretation of small molecules, a phenomenon known as quorum sensing (QS). We hypothesized that QS compounds extruded by could be interpreted by -a form of interspecies communication. We interrogate the structure-activity relationship within the recently discovered pyrone QS network and reveal the exquisite structural features required for targeted phenotypic behavior.

Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung.

The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown.

Bile Acid Signal Molecules Associate Temporally with Respiratory Inflammation and Microbiome Signatures in Clinically Stable Cystic Fibrosis Patients.

Cystic fibrosis (CF) is a congenital disorder resulting in a multisystemic impairment in ion homeostasis. The subsequent alteration of electrochemical gradients severely compromises the function of the airway epithelia. These functional changes are accompanied by recurrent cycles of inflammation-infection that progressively lead to pulmonary insufficiency.

Exploring the synthetic potential of a marine transaminase including discrimination at a remote stereocentre.

The marine transaminase, P-ω-TA, can be employed for the transamination from 1-aminotetralins and 1-aminoindanes with differentiation of stereochemistry at both the site of reaction and at a remote stereocentre resulting in formation of ketone products with up to 93% ee. While 4-substituents are tolerated on the tetralin core, the presence of 3- or 8-substituents is not tolerated by the transaminase. In general P-ω-TA shows capacity for remote diastereoselectivity, although both the stereoselectivity and efficiency are dependent on the specific substrate structure.

Draft Genome Sequences of Three Pseudomonas fluorescens Strains Isolated from Marine Sponges Harvested off the West Coast of Ireland.

Three sp. strains isolated from marine sponges have shown potential quorum sensing inhibition (QSI) activity. We sequenced the draft genomes of the three strains with the goal of determining which genes or gene cluster(s) could be potentially involved in the QSI activity.

The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns.

: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise.

Genome mining and characterisation of a novel transaminase with remote stereoselectivity.

Microbial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir.

A structure-function analysis of interspecies antagonism by the 2-heptyl-4-alkyl-quinolone signal molecule from .

In recent years, the alkyl-quinolone molecular framework has already provided a rich source of bioactivity for the development of novel anti-infective compounds. Based on the quorum-sensing signalling molecules 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS) from the nosocomial pathogen , modifications have been developed with markedly enhanced anti-biofilm bioactivity towards important fungal and bacterial pathogens, including and . Here we show that antibacterial activity of HHQ against is species-specific and it requires an exquisite level of structural fidelity within the alkyl-quinolone molecular framework.

Quorum Sensing Signaling Alters Virulence Potential and Population Dynamics in Complex Microbiome-Host Interactomes.

Despite the discovery of the first -acyl homoserine lactone (AHL) based quorum sensing (QS) in the marine environment, relatively little is known about the abundance, nature and diversity of AHL QS systems in this diverse ecosystem. Establishing the prevalence and diversity of AHL QS systems and how they may influence population dynamics within the marine ecosystem, may give a greater insight into the evolution of AHLs as signaling molecules in this important and largely unexplored niche. Microbiome profiling of and BD1268 sponge samples identified several potential QS active genera.

Exposure to Bile Leads to the Emergence of Adaptive Signaling Variants in the Opportunistic Pathogen .

The chronic colonization of the respiratory tract by the opportunistic pathogen is the primary cause of morbidity and mortality in cystic fibrosis (CF) patients. has been shown to undergo extensive genomic adaptation facilitating its persistence within the CF lung allowing it to evade the host immune response and outcompete co-colonizing residents of the lung microbiota. However, whilst several studies have described the various mutations that frequently arise in clinical isolates of , the environmental factors governing the emergence of these genetic variants is less well characterized.

Genome Sequence of sp. JM45, a Bacterial Strain Isolated from a Marine Sponge with a Dual Quorum Sensing Inhibition Activity.

The draft genome sequence of sp. strain JM45, isolated from a marine sponge harvested off the west coast of Ireland, is reported here. Quorum sensing and quorum sensing inhibition activities have been reported recently for this bacterium, and genomic analysis supports its potential use for novel therapeutic development.

Harnessing Marine Biocatalytic Reservoirs for Green Chemistry Applications through Metagenomic Technologies.

In a demanding commercial world, large-scale chemical processes have been widely utilised to satisfy consumer related needs. Chemical industries are key to promoting economic growth and meeting the requirements of a sustainable industrialised society. The market need for diverse commodities produced by the chemical industry is rapidly expanding globally.

The expanding horizon of alkyl quinolone signalling and communication in polycellular interactomes.

Population dynamics within natural ecosystems is underpinned by microbial diversity and the heterogeneity of host-microbe and microbe-microbe interactions. Small molecule signals that intersperse between species have been shown to govern many virulence-related processes in established and emerging pathogens. Understanding the capacity of microbes to decode diverse languages and adapt to the presence of 'non-self' cells will provide an important new direction to the understanding of the 'polycellular' interactome.

Coumarin: a novel player in microbial quorum sensing and biofilm formation inhibition.

Antibiotic resistance is a growing threat worldwide, causing serious problems in the treatment of microbial infections. The discovery and development of new drugs is urgently needed to overcome this problem which has greatly undermined the clinical effectiveness of conventional antibiotics. An intricate cell-cell communication system termed quorum sensing (QS) and the coordinated multicellular behaviour of biofilm formation have both been identified as promising targets for the treatment and clinical management of microbial infections.

Rethinking the bile acid/gut microbiome axis in cancer.

Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles.

Rapid Electrochemical Detection of Pseudomonas aeruginosa Signaling Molecules by Boron-Doped Diamond Electrode.

As the leading cause of morbidity and mortality of cystic fibrosis (CF) patients, early detection of Pseudomonas aeruginosa (PA) is critical in the clinical management of this pathogen. Herein, we describe rapid and sensitive electroanalytical methods using differential pulse voltammetry (DPV) at a boron-doped diamond (BDD) electrode for the detection of PA signaling biomolecules. Monitoring the production of key signaling molecules in bacterial cultures of P.