Inhibition of twitching motility by quinolones produced by .

Twitching motility in is a key virulence factor linked to antibiotic resistance and pathogenicity. This study revealed that the quinolone signal (PQS) and hydroxy-containing quinolones significantly inhibit motility without affecting bacterial growth, highlighting their potential as targets for controlling bacterial virulence.

Four component Ugi reaction based small-molecule probes for integrated phenotypic screening.

Quorum-sensing (QS) is a cell density-dependent signaling pathway regulated by gene expression for intra- and interspecies communication. We have targeted QS activity in Pseudomonas aeruginosa, an opportunistic human pathogen that causes disease in immunocompromised patients, with a set of probes containing a variety of functional groups, including photoreactive (diazirine) and affinity (alkyne) moieties, that were synthesized using a four-component Ugi reaction (Ugi-4CR).

Metabolic inputs in the probiotic bacterium Lacticaseibacillus rhamnosus contribute to cell-wall remodeling and increased fitness.

Lacticaseibacillus rhamnosus GG (LGG) is a Gram-positive beneficial bacterium that resides in the human intestinal tract and belongs to the family of lactic acid bacteria (LAB). This bacterium is a widely used probiotic and was suggested to provide numerous benefits for human health. However, as in most LAB strains, the molecular mechanisms that mediate the competitiveness of probiotics under different diets remain unknown.

The reduction of environmentally abundant iron oxides by the methanogen .

Microbial dissimilatory iron reduction is a fundamental respiratory process that began early in evolution and is performed in diverse habitats including aquatic anoxic sediments. In many of these sediments microbial iron reduction is not only observed in its classical upper zone, but also in the methane production zone, where low-reactive iron oxide minerals are present. Previous studies in aquatic sediments have shown the potential role of the archaeal methanogen Methanosarcinales in this reduction process, and their use of methanophenazines was suggested as an advantage in reducing iron over other iron-reducing bacteria.

Chemical Modification of a Bacterial Siderophore by a Competitor in Dual-Species Biofilms.

Chemical communication between competing bacteria in multi-species environments often enables both species to adapt and survive, and perhaps even thrive. P. aeruginosa and S.

Indole intercepts the communication between enteropathogenic and .

Reported numbers of diarrheal samples exhibiting co-infections or multiple infections, with two or more infectious agents, are rising, likely due to advances in bacterial diagnostic techniques. Bacterial species detected in these samples include () and enteropathogenic (EPEC), which infect the small intestine and are associated with high mortality rates. It has previously been reported that EPEC exhibit enhanced virulence in the presence of owing to their ability to sense and respond to elevated concentrations of cholera autoinducer 1 (CAI-1), which is the primary quorum-sensing (QS) molecule produced by .

Context-dependent differences in the functional responses of Lactobacillaceae strains to fermentable sugars.

Lactobacillaceae are Gram-positive rods, facultative anaerobes, and belong to the lactic acid bacteria (LAB) that frequently serve as probiotics. We systematically compared five LAB strains for the effects of different carbohydrates on their free-living and biofilm lifestyles. We found that fermentable sugars triggered an altered carrying capacity with strain specificity during planktonic growth.

Transcription-replication coordination revealed in single live cells.

The coexistence of DNA replication and transcription during S-phase requires their tight coordination to prevent harmful conflicts. While extensive research revealed important mechanisms for minimizing these conflicts and their consequences, little is known regarding how the replication and transcription machinery are coordinated in real-time. Here, we developed a live-cell imaging approach for the real-time monitoring of replisome progression and transcription dynamics during a transcription-replication encounter.

Mammalian gut metabolomes mirror microbiome composition and host phylogeny.

In the past decade, studies on the mammalian gut microbiome have revealed that different animal species have distinct gut microbial compositions. The functional ramifications of this variation in microbial composition remain unclear: do these taxonomic differences indicate microbial adaptations to host-specific functionality, or are these diverse microbial communities essentially functionally redundant, as has been indicated by previous metagenomics studies? Here, we examine the metabolic content of mammalian gut microbiomes as a direct window into ecosystem function, using an untargeted metabolomics platform to analyze 101 fecal samples from a range of 25 exotic mammalian species in collaboration with a zoological center. We find that mammalian metabolomes are chemically diverse and strongly linked to microbiome composition, and that metabolome composition is further correlated to the phylogeny of the mammalian host.

A Bacterial Quorum Sensing Molecule Elicits a General Stress Response in .

Bacteria assess their population density through a chemical communication mechanism termed quorum sensing, in order to coordinate group behavior. Most research on quorum sensing has focused primarily on its role as an intraspecies chemical signaling mechanism that enables the regulation of certain phenotypes through targeted gene expression. However, in recent years several seminal studies have revealed important phenomena in which quorum sensing molecules appear to serve additional roles as interspecies signals that may regulate microbial ecology.

Insight on the Order of Regioselective Ultrafast Formation of Disulfide Bonds in (Antimicrobial) Peptides and Miniproteins.

Disulfide-rich peptides and proteins are among the most fascinating bioactive molecules. The difficulties associated with the preparation of these targets have prompted the development of various chemical strategies. Nevertheless, the production of these targets remains very challenging or elusive.

Short-chain reactive probes as tools to unravel the quorum sensing regulon.

In recent years, the world has seen a troubling increase in antibiotic resistance among bacterial pathogens. In order to provide alternative strategies to combat bacterial infections, it is crucial deepen our understanding into the mechanisms that pathogens use to thrive in complex environments. Most bacteria use sophisticated chemical communication systems to sense their population density and coordinate gene expression in a collective manner, a process that is termed "quorum sensing" (QS).

An inside look at a biofilm: flagella biotracking.

The opportunistic pathogen, , a flagellated bacterium, is one of the top model organisms for biofilm studies. To elucidate the location of bacterial flagella throughout the biofilm life cycle, we developed a new flagella biotracking tool. Bacterial flagella were site-specifically labeled via genetic code expansion.

Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites.

Background: Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections.

Immunoediting role for major vault protein in apoptotic signaling induced by bacterial -acyl homoserine lactones.

The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Here, we report the use of photoactive probes to identify MVP as a target of the -(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including A treatment of normal and cancer cells with C12 or other -acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death.

Glycosylation of N-hydroxy-pipecolic acid equilibrates between systemic acquired resistance response and plant growth.

N-hydroxy-pipecolic acid (NHP) activates plant systemic acquired resistance (SAR). Enhanced defense responses are typically accompanied by deficiency in plant development and reproduction. Despite of extensive studies on SAR induction, the effects of NHP metabolism on plant growth remain largely unclear.

Auto-deconvolution and molecular networking of gas chromatography-mass spectrometry data.

We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography-mass spectrometry (GC-MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC-MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization and quantifies the reproducibility of fragmentation patterns across samples.

Modulation of Bacterial Quorum Sensing by Strigolactones.

Strigolactones are plant hormones with multiple roles that act as signaling molecules in many processes in the rhizosphere. In recent years, additional roles of strigolactones in nature have emerged, and here we report that strigolactones are able to modulate bacterial quorum sensing (QS) in the human pathogen .

Synthesis and Evaluation of Indole-Based Autoinducers on Quorum Sensing in .

() uses the autoinducer CAI-1 (cholera autoinducer 1) and several linked quorum sensing systems in order to efficiently sense its ever-changing environment and optimally coordinate population-wide gene expression. Indole has been reported as an important signal that is sensed by , and here, we report the synthesis and evaluation of a focused library of synthetic indole-CAI-1 derivatives as tools to probe quorum sensing (QS) in this human pathogen. Our results show interesting and diverging effects for several conjugates, as compared to CAI-1, on virulence factor production and biofilm formation.

Silver-doped laser-induced graphene for potent surface antibacterial activity and anti-biofilm action.

Previously, laser-induced graphene (LIG) coated surfaces were shown to resist biofilm growth, although the material was not strongly antibacterial. Here, we show LIG surfaces doped with silver nanoparticles (Ag0 or AgNPs) as highly antibacterial surfaces. Starting from AgNO3 polyethersulfone (PES) polymer substrates, silver nanoparticles between 5-10 nm were generated in situ during the lasing process and stably embedded in the fibrous and porous structure of LIG in a single step.

Vibrio cholerae autoinducer-1 enhances the virulence of enteropathogenic Escherichia coli.

Diarrhoea is the second leading cause of death in children under the age of five. The bacterial species, Vibrio cholerae and enteropathogenic Escherichia coli (EPEC), are among the main pathogens that cause diarrhoeal diseases, which are associated with high mortality rates. These two pathogens have a common infection site-the small intestine.

Indole Derivatives Maintain the Status Quo Between Beneficial Biofilms and Their Plant Hosts.

Biofilms formed by bacteria on plant roots play an important role in maintaining an optimal rhizosphere environment that supports plant growth and fitness. is a potent plant growth promoter, forming biofilms that play a key role in protecting the host from fungal and bacterial infections. In this work, we demonstrate that the development of biofilms is antagonized by specific indole derivatives that accumulate during symbiotic interactions with plant hosts.

Proteome-wide mapping of PQS-interacting proteins in .

The opportunistic human pathogen secretes 2-heptyl-3-hydroxy-4-quinolone (PQS), a quorum sensing (QS) signal that regulates the expression of numerous virulence genes. Here we report the development and application of chemical probes to globally map quinolone binding proteins. The revealed quinolone interactome contains both known as well as newly identified virulence factors and presents new targets for the treatment of bacterial infections.

Reciprocal Interactions between Membrane Bilayers and S. aureus PSMα3 Cross-α Amyloid Fibrils Account for Species-Specific Cytotoxicity.

Phenol-soluble modulin α3 (PSMα3) is a functional amyloid secreted by the pathogenic bacterium Staphylococcus aureus. This 22-residue peptide serves as a key virulence determinant, toxic to human cells via the formation of unique cross-α amyloid-like fibrils. We demonstrate that bilayer vesicles accelerated PSMα3 fibril formation, and the fibrils, in turn, inserted deeply into bilayers mimicking mammalian cell membranes, accounting for PSMα3 cellular toxicity.