Biology subjects

Moreno, D. M.

Publications and source records attributed to Moreno, D. M..

3 recordsLinked to original sources

bioRxiv2023

MolecularWebXR: Multiuser discussions about chemistry and biology in immersive and inclusive VR

MolecularWebXR is a new website for education, science communication and scientific peer discussion in chemistry and biology, based on modern web-based Virtual Reality (VR) and Augmented Reality (AR). With no installs as it is all web-served, MolecularWebXR enables multiple users to simultaneously explore, communicate and discuss concepts about chemistry and biology in immersive 3D environments, by manipulating and passing around objects with their bare hands and pointing at different elements with natural hand gestures. User may either be present in the same real space or distributed around the world, in the latter case talking naturally with each other thanks to built-in audio features. Although MolecularWebXR is most immersive when running in the web browsers of high-end AR/VR headsets, its WebXR core also allows participation by users with consumer devices such as smartphones, possibly inserted into cardboard goggles for deeper immersivity, or even in computers and tablets. MolecularWebXR comes with preset VR rooms that cover topics from general, inorganic and organic chemistry, biophysics and structural biology, and general biology; besides, new content can be added at will through moleculARwebs PDB2AR tool or by contacting the lead authors. We verified MolecularWebXRs ease of use and versatility by people aged 12-80 years old in entirely virtual sessions or in mixed real-virtual sessions at various science outreach events, in courses at the bachelor, masters and early doctoral levels, in scientific collaborations, and in conference lectures. MolecularWebXR is available for free use without registration at https://molecularwebxr.org, and a blog post version of this preprint with embedded videos is available at https://go.epfl.ch/molecularwebxr-blog-post.

scientific communication and education↗

bioRxiv2023

Selective inhibition of the amyloid matrix of Escherichia coli biofilms by a bifunctional microbial metabolite

The propensity of bacteria to grow collectively in communities known as biofilms and their ability to overcome clinical treatments in this condition has become a major medical problem, emphasizing the need for anti-biofilm strategies. Antagonistic microbial interactions have extensively served as searching platforms for antibiotics, but their potential as sources for anti-biofilm compounds has barely been exploited. By screening for microorganisms that in agar-set pairwise interactions could antagonize Escherichia colis ability to form macrocolony biofilms, we found that the soil bacterium Bacillus subtilis strongly inhibits the synthesis of amyloid fibers -known as curli-, which are the primary extracellular matrix (ECM) components of E. coli biofilms. We identified bacillaene, a B. subtilis hybrid non-ribosomal peptide/polyketide metabolite, previously described as a bacteriostatic antibiotic, as the effector molecule. We found that bacillaene combines both antibiotic and anti-curli functions in a concentration-dependent order that potentiates the ecological competitiveness of B. subtilis, highlighting bacillaene as a metabolite naturally optimized for microbial inhibition. Our studies revealed that bacillaene inhibits curli by directly impeding the assembly of the CsgB and CsgA curli subunits into amyloid fibers. Moreover, we found that curli inhibition occurs despite E. coli attempts to reinforce its protective ECM by inducing curli genes via a RpoS-mediated competition sensing response trigged by the threatening presence of B. subtilis. Overall, our findings illustrate the relevance of exploring microbial interactions not only for finding compounds with novel and unique activities, but for uncovering additional functions of compounds previously categorized as antibiotics. IMPORTANCEWhile traditionally serving as sources for novel antibiotics, microbial interactions have a great potential -yet to be more intensely exploited- as sources for compounds with anti-biofilm activities among other functions. Exploring such potential, we uncovered an anti-curli amyloid activity of bacillaene, a B. subtilis secondary metabolite, that prevents E. coli biofilm morphogenesis. We demonstrated that bacillaene inhibits curli by interfering with the assembly of curli subunits into amyloid fibers and that such inhibition occurs despite E. coli fights to reinforce its protective amyloid matrix. Moreover, we showed that bacillaene combines this anti-curli activity with a previously assigned antibiotic activity in a concentration-dependent order that potentiates the inhibitory effect against curli-based E. coli biofilms. The finding of additional activities of compounds previously characterized as antibiotics, as here demonstrated for bacillaene, is relevant to understand both the actual roles of secondary metabolites in modulating microbial interactions in natural niches and the potential implications of the combined activities in therapeutic applications to treat bacterial infections.

microbiology↗

bioRxiv2021

β-lactamase remodeling and evolution of collateral resistance in hypermutator Pseudomonas aeruginosa upon long-term antibiotic therapy

Antibiotic resistance development has been studied using approaches that range from laboratory experimental evolution, surveillance and epidemiology, to clinical isolate sequencing. However, evolutionary trajectories depend on the environment in which selection takes place, compelling to address evolutionary analyses in antibiotic-treated patients, to embrace the whole inherent environmental complexities as well as their dynamics over time. Herein, we address the complexity of the bacterial adaptive response to changing antibiotic selective pressures by studying the long-term in-patient evolution of a broad diversity of {beta}-lactam resistant Pseudomonas aeruginosa clones. By using mutational and ultra-deep amplicon sequencing, we analyzed multiple generations of a P. aeruginosa hypermutator strain persisting for more than 26 years of chronic infection in the airways of a cystic fibrosis (CF) patient. We identified the accumulation of multiple alterations targeting the chromosomally encoded class C {beta}-lactamase (blaPDC), providing structural and functional protein changes that resulted in a continuous enhancement of its catalytic efficiency and high level of cephalosporin resistance. This evolution was linked to the persistent treatment with ceftazidime, which we demonstrate selected for variants with robust catalytic activity against this expanded-spectrum cephalosporin. Surprisingly, "a gain of function" of collateral resistance towards ceftolozane, a more recently introduced cephalosporin that was not prescribed to this patient, was also observed and the biochemical basis of this cross-resistance phenomenon was elucidated. This work unveils the diversity of evolutionary trajectories driven by bacteria in the natural CF environmental setting, towards a multidrug resistant phenotype after years of antibiotic treatment against a formidable pathogen.

microbiology↗