The Influence of Permeability through Bacterial Porins in Whole-Cell Compound Accumulation.

The lack of new drugs for Gram-negative pathogens is a global threat to modern medicine. The complexity of their cell envelope, with an additional outer membrane, hinders internal accumulation and thus, the access of molecules to their targets. Our limited understanding of the molecular basis for compound influx and efflux from these pathogens is a major bottleneck for the discovery of effective antibacterial compounds. Here we analyse the correlation between the whole-cell compound accumulation of ~200 molecules and their predicted porin permeability coefficient (influx), using a recently developed scoring function. We found a strong linear relationship (74%) between the two, confirming porins key in compound uptake in Gram-negative bacteria. The analysis of this unique dataset aids to better understand the molecular descriptors behind whole-cell accumulation and molecular uptake in Gram-negative bacteria

A different perspective for nonphotochemical quenching in plant antenna complexes

Light-harvesting complexes of plants exert a dual function of light-harvesting (LH) and photoprotection through processes collectively called nonphotochemical quenching (NPQ). While LH processes are relatively well characterized, those involved in NPQ are less understood. Here, we characterize the quenching mechanisms of CP29, a minor LHC of plants, through the integration of two complementary enhanced-sampling techniques, dimensionality reduction schemes, electronic calculations and the analysis of cryo-EM data in the light of the predicted conformational ensemble. Our study reveals that the switch between LH and quenching state is more complex than previously thought. Several conformations of the lumenal side of the protein occur and differently affect the pigments’ relative geometries and interactions. Moreover, we show that a quenching mechanism localized on a single chlorophyll-carotenoid pair is not sufficient but many chlorophylls are simultaneously involved. In such a diffuse mechanism, short-range interactions between each carotenoid and different chlorophylls combined with a protein-mediated tuning of the carotenoid excitation energies have to be considered in addition to the commonly suggested Coulomb interactions

Porins and small-molecule translocation across the outer membrane of Gram-negative bacteria

Gram-negative bacteria and their complex cell envelope, which comprises an outer membrane and an inner membrane, are an important and attractive system for studying the translocation of small molecules across biological membranes. In the outer membrane of Enterobacteriaceae, trimeric porins control the cellular uptake of small molecules, including nutrients and antibacterial agents. The relatively slow porin-mediated passive uptake across the outer membrane and active efflux via efflux pumps in the inner membrane creates a permeability barrier. The synergistic action of outer membrane permeability, efflux pump activities and enzymatic degradation efficiently reduces the intracellular concentrations of small molecules and contributes to the emergence of antibiotic resistance. In this Review, we discuss recent advances in our understanding of the molecular and functional roles of general porins in small-molecule translocation in Enterobacteriaceae and consider the crucial contribution of porins in antibiotic resistance

MOMP from Campylobacter jejuni Is a Trimer of 18-Stranded β-Barrel Monomers with a Ca²⁺ Ion Bound at the Constriction Zone

The Gram-negative organism Campylobacter jejuni is the major cause of food poisoning. Unlike Escherichia coli, which has two major porins, OmpC and OmpF, C. jejuni has one, termed major outer membrane protein (MOMP) through which nutrients and antibiotics transit. We report the 2.1-Å crystal structure of C. jejuni MOMP expressed in E. coli and a lower resolution but otherwise identical structure purified directly from C. jejuni. The 2.1-Å resolution structure of recombinant MOMP showed that although the protein has timeric arrangement similar to OmpC, it is an 18-stranded, not 16-stranded, β-barrel. The structure has identified a Ca²⁺ bound at the constriction zone, which is functionally significant as suggested by molecular dynamics and single-channel experiments. The water-filled channel of MOMP has a narrow constriction zone, and single-molecule studies show a monomeric conductivity of 0.7 ± 0.2 nS and a trimeric conductance of 2.2 ± 0.2 nS. The ion neutralizes negative charges at the constriction zone, reducing the transverse electric field and reversing ion selectivity. Modeling of the transit of ciprofloxacin, an antibiotic of choice for treating Campylobacter infection, through the pore of MOMP reveals a trajectory that is dependent upon the presence metal ion

Comunicar ciencia en México: fundamentos, estudios y experiencias

Este libro representa un nuevo hito en la consolidación de los estudios sobre comunicación, ciencia y cultura en América Latina pues articula un extenso intercambio de voces y experiencias que nutren la reflexión y el debate colectivo sobre el conocimiento tecnocientífico y su comunicación pública y destaca la participación profesional de las mujeres en este campo, así como los modos en que la comunicación pública de la ciencia en México se ha ido desplazando del conocimiento científico, en sí mismo, para centrarse en la comprensión y puesta en común de las muy complejas y diversas problemáticas que impactan la vida social y natural.ITESO, A.C

Multiwavelength observations of the extraordinary accretion event AT2021lwx

We present observations from X-ray to mid-infrared wavelengths of the most energetic non-quasar transient ever observed, AT2021lwx. Our data show a single optical brightening by a factor $>100$ to a luminosity of $7\times10^{45}$ erg s$^{-1}$, and a total radiated energy of $1.5\times10^{53}$ erg, both greater than any known optical transient. The decline is smooth and exponential and the ultra-violet - optical spectral energy distribution resembles a black body with temperature $1.2\times10^4$ K. Tentative X-ray detections indicate a secondary mode of emission, while a delayed mid-infrared flare points to the presence of dust surrounding the transient. The spectra are similar to recently discovered optical flares in known active galactic nuclei but lack some characteristic features. The lack of emission for the previous seven years is inconsistent with the short-term, stochastic variability observed in quasars, while the extreme luminosity and long timescale of the transient disfavour the disruption of a single solar-mass star. The luminosity could be generated by the disruption of a much more massive star, but the likelihood of such an event occurring is small. A plausible scenario is the accretion of a giant molecular cloud by a dormant black hole of $10^8 - 10^9$ solar masses. AT2021lwx thus represents an extreme extension of the known scenarios of black hole accretion.Comment: 11 pages, 5 figures, Accepted for publication in MNRA

A Highly Intensified ART Regimen Induces Long-Term Viral Suppression and Restriction of the Viral Reservoir in a Simian AIDS Model

Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART) in a wide range of viremic conditions (103–107 viral RNA copies/mL) in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART) consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir), an integrase inhibitor (raltegravir), a protease inhibitor (ritonavir-boosted darunavir) and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL) after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*105 cells) in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR+) effector memory CD4+ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing potential cures for AIDS

“Help! I Need Somebody”: Music as a global resource for obtaining wellbeing goals in times of crisis

Health and self-regulatio