Exploring fluorinated heptose phosphate analogues as inhibitors of HldA and HldE, key enzymes in the biosynthesis of lipopolysaccharide.

The growing threat of bacterial resistance to antibiotics has led to the rise of anti-virulence strategies as a promising approach. These strategies aim to disarm bacterial pathogens and improve their clearance by the host immune system. Lipopolysaccharide, a key virulence factor in Gram-negative bacteria, has been identified as a potential target for anti-virulence agents.

The end of the reign of a "master regulator''? A defect in function of the LasR quorum sensing regulator is a common feature of isolates.

, a bacterium causing infections in immunocompromised individuals, regulates several of its virulence functions using three interlinked quorum sensing (QS) systems (, , and ). Despite its presumed importance in regulating virulence, dysfunction of the system regulator LasR occurs frequently in strains isolated from various environments, including clinical infections. This newfound abundance of LasR-defective strains calls into question existing hypotheses regarding their selection.

Structural characterization of a nonionic rhamnolipid from Burkholderia lata.

We present the isolation and structural characterization of a novel nonionic dirhamnolipid methyl ester produced by the bacterium Burkholderia lata. The structure and the absolute configuration of the isolated dirhamnolipid bearing a symmetrical C-C methyl ester chain were thoroughly investigated through chemical degradation and spectroscopic methods including 1D and 2D NMR analysis, HR-ESI-TOF-MS, chiral GC-MS, and polarimetry. Our work represents the first mention in the literature of a rhamnolipid methyl ester from Burkholderia species.

Inhibition of PQS signaling by the Pf bacteriophage protein PfsE enhances viral replication in Pseudomonas aeruginosa.

Quorum sensing, a bacterial signaling system that coordinates group behaviors as a function of cell density, plays an important role in regulating viral (phage) defense mechanisms in bacteria. The opportunistic pathogen Pseudomonas aeruginosa is a model system for the study of quorum sensing. P.

Simple method for quantification of anionic biosurfactants in aqueous solutions.

Biosurfactants are microbial products that have applications as cleaning agents, emulsifiers, and dispersants. Detection and quantification of biosurfactants can be done by various methods, including colorimetric tests, high performance liquid chromatography (HPLC) coupled to several types of detectors, and tests that take advantage of biosurfactants reducing surface tension of aqueous liquids, allowing for spreading and droplet formation of oils. We present a new and simple method for quantifying biosurfactants by their ability, on paper, to reduce surface tension of aqueous solutions, causing droplet dispersion on an oiled surface in correlation with biosurfactant content.

Surface growth of reveals a regulatory effect of 3-oxo-C-homoserine lactone in the absence of its cognate receptor, LasR.

The bacterium colonizes and thrives in many environments, in which it is typically found in surface-associated polymicrobial communities known as biofilms. Adaptation to this social behavior is aided by quorum sensing (QS), an intercellular communication system pivotal in the expression of social traits. Regardless of its importance in QS regulation, the loss of function of the master regulator LasR is now considered a conserved adaptation of , irrespective of the origin of the strains.

Inhibition of PQS signaling by the Pf bacteriophage protein PfsE enhances viral replication in .

Quorum sensing, a bacterial signaling system that coordinates group behaviors as a function of cell density, plays an important role in regulating viral (phage) defense mechanisms in bacteria. The opportunistic pathogen is a model system for the study of quorum sensing. is also frequently infected by Pf prophages that integrate into the host chromosome.

Emergence of Small Colony Variants Is an Adaptive Strategy Used by Pseudomonas aeruginosa to Mitigate the Effects of Redox Imbalance.

The ability to generate a subpopulation of small colony variants (SCVs) is a conserved feature of Pseudomonas aeruginosa and could represent a key adaptive strategy to colonize and persist in multiple niches. However, very little is known about the role of the SCV phenotype, the conditions that promote its emergence, and its possible involvement in an adaptive strategy. In the present work, we investigated the selective conditions promoting the emergence of SCVs from the prototypical strain PA14, which readily forms SCVs in nonagitated standing cultures.

Community composition shapes microbial-specific phenotypes in a cystic fibrosis polymicrobial model system.

Interspecies interactions can drive the emergence of unexpected microbial phenotypes that are not observed when studying monocultures. The cystic fibrosis (CF) lung consists of a complex environment where microbes, living as polymicrobial biofilm-like communities, are associated with negative clinical outcomes for persons with CF (pwCF). However, the current lack of in vitro models integrating the microbial diversity observed in the CF airway hampers our understanding of why polymicrobial communities are recalcitrant to therapy in this disease.

Pseudomonas aeruginosa Strains from Both Clinical and Environmental Origins Readily Adopt a Stable Small-Colony-Variant Phenotype Resulting from Single Mutations in c-di-GMP Pathways.

A subpopulation of small-colony variants (SCVs) is a frequently observed feature of Pseudomonas aeruginosa isolates obtained from colonized cystic fibrosis lungs. Since most SCVs have until now been isolated from clinical samples, it remains unclear how widespread the ability of P. aeruginosa strains to develop this phenotype is and what the genetic mechanism(s) behind the emergence of SCVs are according to the origin of the isolate.

Surface Motility Favors Codependent Interaction between Pseudomonas aeruginosa and Burkholderia cenocepacia.

Interactions between different bacterial species shape bacterial communities and their environments. The opportunistic pathogens Pseudomonas aeruginosa and Burkholderia cenocepacia both can colonize the lungs of individuals affected by cystic fibrosis. Using the social surface behavior called swarming motility as a study model, we noticed intricate interactions between B.

Fluoride-Controlled Riboswitch-Based Dampening of Gene Expression for Cloning Potent Promoters.

Bioreporter systems based on detectable enzyme activity, such as that of beta-galactosidase or luciferase, are key in novel bacterial promoter discovery and study. While these systems permit quantification of gene expression, their use is limited by the toxicity of the expressed reporter enzymes in a given host. Indeed, the most potent promoters may be overlooked if their activity causes a lethal overproduction of the reporter genes when screening for transcriptional activity of potential promoter sequences with the cassette.

Altered Strategies to Inhibit Surface Colonies.

and infections frequently co-localize in lungs of immunocompromised patients and individuals with cystic fibrosis (CF). The antifungal activity of has been described for its filtrates. Pyoverdine and pyocyanin are the principal antifungal molecules active against biofilm metabolism present in iron-limited or iron-replete planktonic culture filtrates, respectively.

Total Synthesis of a Chimeric Glycolipid Bearing the Partially Acetylated Backbone of Sponge-Derived Agminoside E.

We describe the total synthesis of a chimeric glycolipid bearing both the partially acetylated backbone of sponge-derived agminoside E and the ()-3-hydroxydecanoic acid chain of bacterial rhamnolipids. The branched pentaglucolipid skeleton was achieved using a [3 + 2] disconnection approach. The β-(1 → 2) and β-(1 → 4)-glycosidic bonds were synthesized through a combination of NIS/Yb(OTf)- and TMSOTf-mediated stereoselective glycosylations of thiotolyl, -phenyltrifluoroacetimidate, and trichloroacetimidate donors.

Pseudomonas aeruginosa isolates defective in function of the LasR quorum sensing regulator are frequent in diverse environmental niches.

The saprophyte Pseudomonas aeruginosa is a versatile opportunistic pathogen causing infections in immunocompromised individuals. To facilitate its adaptation to a large variety of niches, this bacterium exploits population density-dependent gene regulation systems called quorum sensing (QS). In P.

Total synthesis, isolation, surfactant properties, and biological evaluation of ananatosides and related macrodilactone-containing rhamnolipids.

Rhamnolipids are a specific class of microbial surfactants, which hold great biotechnological and therapeutic potential. However, their exploitation at the industrial level is hampered because they are mainly produced by the opportunistic pathogen . The non-human pathogenic bacterium is an alternative producer of rhamnolipid-like metabolites containing glucose instead of rhamnose residues.

Total synthesis of the proposed structures of gladiosides I and II.

Burkholderia gladioli is a Gram-negative bacterium that biosynthesizes a cocktail of potent antimicrobial compounds, including the antifungal phenolic glycoside sinapigladioside. Herein, we report the total synthesis of the proposed structures of gladiosides I and II, two structurally related phenolic glycosides previously isolated from B. gladioli OR1 cultures.

Quorum Sensing Controls Both Rhamnolipid and Polyhydroxyalkanoate Production in Through ScmR Regulation.

Rhamnolipids are surface-active agents of microbial origin used as alternatives to synthetic surfactants. is a non-pathogenic rhamnolipid-producing bacterium that could represent an interesting candidate for use in commercial processes. However, current bioprocesses for rhamnolipid production by this bacterium are not efficient enough, mainly due to low yields.

Burkholderia thailandensis Methylated Hydroxyalkylquinolines: Biosynthesis and Antimicrobial Activity in Cocultures.

The bacterium produces an arsenal of secondary metabolites that have diverse structures and roles in the ecology of this soil-dwelling bacterium. In coculture experiments, strain E264 secretes an antimicrobial that nearly eliminates another soil bacterium, strain 168. To identify the antimicrobial, we used a transposon mutagenesis approach.

Synthesis and Antimicrobial Activity of -Related 4-Hydroxy-3-methyl-2-alkenylquinolines (HMAQs) and Their -Oxide Counterparts.

The genus offers a promising potential in medicine because of the diversity of biologically active natural products encoded in its genome. Some pathogenic spp. biosynthesize a specific class of antimicrobial 2-alkyl-4(1)-quinolones, i.

Cationic Ru Cyclopentadienyl Complexes with Antifungal Activity against Several Candida Species.

Fungal infections, including those caused by antifungal-resistant Candida, are a very challenging health problem worldwide. Whereas different ruthenium complexes were previously studied for their anti-Candida potential, Ru-cyclopentadienyl complexes were overlooked. Here, we report an antifungal activity assessment of three Ru-cyclopentadienyl complexes with some insights into their potential mode of action.

PqsE Is Essential for RhlR-Dependent Quorum Sensing Regulation in Pseudomonas aeruginosa.

The bacterium has emerged as a central threat in health care settings and can cause a large variety of infections. It expresses an arsenal of virulence factors and a diversity of survival functions, many of which are finely and tightly regulated by an intricate circuitry of three quorum sensing (QS) systems. The system is considered at the top of the QS hierarchy and activates the and systems.

Swarming motility growth favours the emergence of a subpopulation of Pseudomonas aeruginosa quorum-sensing mutants.

Pseudomonas aeruginosa exploits several types of motility behaviours to colonize diverse environments. One of these is swarming motility, a coordinated group movement on a semi-solid surface. This bacterium needs to express a functional flagellum and produce rhamnolipids to display this type of social motility.

ScmR, a Global Regulator of Gene Expression, Quorum Sensing, pH Homeostasis, and Virulence in .

The nonpathogenic soil saprophyte is a member of the group, which also comprises the closely related human pathogens and responsible for the melioidosis and glanders diseases, respectively. ScmR, a recently identified LysR-type transcriptional regulator in , acts as a global transcriptional regulator throughout the stationary phase and modulates the production of a wide range of secondary metabolites, including -acyl-l-homoserine lactones and 4-hydroxy-3-methyl-2-alkylquinolines and virulence in the nematode worm host model, as well as several quorum sensing (QS)-dependent phenotypes. We have investigated the role of ScmR in strain E264 during the exponential phase.

Phenylacetyl Coenzyme A, Not Phenylacetic Acid, Attenuates CepIR-Regulated Virulence in Burkholderia cenocepacia.

During phenylalanine catabolism, phenylacetic acid (PAA) is converted to phenylacetyl coenzyme A (PAA-CoA) by a ligase, PaaK, and then PAA-CoA is epoxidized by a multicomponent monooxygenase, PaaABCDE, before further degradation through the tricarboxylic acid (TCA) cycle. In the opportunistic pathogen , loss of attenuates virulence factor expression, which is under the control of the LuxIR-like quorum sensing (QS) system, CepIR. To further investigate the link between CepIR-regulated virulence and PAA catabolism, we created knockout mutants of the first step of the pathway (PAA-CoA synthesis by PaaK) and characterized them in comparison to a mutant using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and virulence assays.