Search

Biofilm inhibition by exogenous molecules has been an attractive strategy for the development of novel therapeutics. We investigated the biofilm inhibitor taurolithocholic acid (TLCA) and its effects on the specialized metabolism, virulence, and biofilm formation of the clinically relevant bacterium Pseudomonas aeruginosa strain PA14. Our study shows that TLCA alters the specialized metabolism, thereby affecting P. aeruginosa colony biofilm physiology. We observed an upregulation of metabolites correlated to virulence such as the siderophore pyochelin. A wax moth virulence assay confirmed that treatment with TLCA increases the virulence of P. aeruginosa. On the basis of our results, we believe that future endeavors to identify biofilm inhibitors must consider how a putative lead alters the specialized metabolism of a bacterial community to prevent pathogens from entering a highly virulent state.

Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently.sup.1 and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had not to our knowledge been reported before. Over half of the new interactions can be ascribed to bioaccumulation; that is, bacteria storing the drug intracellularly without chemically modifying it, and in most cases without the growth of the bacteria being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes the metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the composition of the community through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioural response of Caenorhabditis elegans to duloxetine. Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner. An analysis of the interactions between 15 drugs and 25 gut bacterial strains shows that bioaccumulation of drugs within bacterial cells is another mechanism through which gut microorganisms can alter drug availability and efficacy., Author(s): Martina Klünemann [sup.1] [sup.9] , Sergej Andrejev [sup.1] [sup.10] , Sonja Blasche [sup.1] [sup.2] , Andre Mateus [sup.1] , Prasad Phapale [sup.1] , Saravanan Devendran [sup.1] , Johanna Vappiani [...]

Adhesion of contaminants on various polymer‐based devices during fluid‐substrate interactions is a common problem that can cause biofouling and corrosion. In this study, hierarchical structures with submicron features on polypropylene (PP), high‐density polyethylene (HDPE), and polycarbonate (PC) are fabricated by femtosecond laser ablation. The effect of the hierarchical structures on surface wettability, droplet impact, and bacterial attachment has been examined. Our results demonstrate that the structured polymeric substrates facilitate large contact angles and minimal interfacial adhesion, allowing droplets to roll off at a low angle of inclination below 5°. Further, rendering the hierarchical structures with a low‐surface‐energy coating can enable the surfaces to exhibit superamphiphobic properties. The low interfacial adhesion properties, as accounted by the large contact angles and small contact angle hysteresis, of such surfaces prevent bacterial attachment and biofilm formation. The findings provide a design principle for creating affordable biofouling resistant surfaces with a submicron topography that can be used for engineering and biomedical devices. [ABSTRACT FROM AUTHOR]

Growth of the mesh-like peptidoglycan (PG) sacculus located between the bacterial inner and outer membranes (OM) is tightly regulated to ensure cellular integrity, maintain cell shape, and orchestrate division. Cytoskeletal elements direct placement and activity of PG synthases from inside the cell, but precise spatiotemporal control over this process is poorly understood. We demonstrate that PG synthases are also controlled from outside of the sacculus. Two OM lipoproteins, LpoA and LpoB, are essential for the function, respectively, of PBP1A and PBP1B, the major E. coli bifunctional PG synthases. Each Lpo protein binds specifically to its cognate PBP and stimulates its transpeptidase activity, thereby facilitating attachment of new PG to the sacculus. LpoB shows partial septal localization, and our data suggest that the LpoB-PBP1B complex contributes to OM constriction during cell division. LpoA/LpoB and their PBP-docking regions are restricted to γ-proteobacteria, providing models for niche-specific regulation of sacculus growth.

In vitro cytotoxicity assessment is indispensable in developing new biodegradable implant materials. Zn, which demonstrates an ideal corrosion rate between Mg‐ and Fe‐based alloys, has been reported to have excellent in vivo biocompatibility. Therefore, modifications aimed at improving Zn's mechanical properties should not degrade its biological response. As sufficient strength, ductility and corrosion behavior required of load‐bearing implants has been obtained in plastically deformed Zn‐3Ag‐0.5Mg, the effect of simultaneous Ag and Mg additions on in vitro cytocompatibility and antibacterial properties was studied, in relation to Zn and Zn‐3Ag. Direct cell culture on samples and indirect extract‐based tests showed almost no significant differences between the tested Zn‐based materials. The diluted extracts of Zn, Zn‐3Ag, and Zn‐3Ag‐0.5Mg showed no cytotoxicity toward MG‐63 cells at a concentration of ≤12.5%. The cytotoxic effect was observed only at high Zn2+ ion concentrations and when in direct contact with metallic samples. The highest LD50 (lethal dose killing 50% of cells) of 13.4 mg/L of Zn2+ ions were determined for the Zn‐3Ag‐0.5Mg. Similar antibacterial activity against Escherichia coli and Staphylococcus aureus was observed for Zn and Zn alloys, so the effect is attributed mainly to the released Zn2+ ions exhibiting bactericidal properties. Most importantly, our experiments indicated the limitations of water‐soluble tetrazolium salt‐based cytotoxicity assays for direct tests on Zn‐based materials. The discrepancies between the WST‐8 assay and SEM observations are attributed to the interference of Zn2+ ions with tetrazolium salt, therefore favoring its transformation into formazan, giving false cell viability quantitative results. [ABSTRACT FROM AUTHOR]