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Fil: Sieira, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina

To reconstruct transmission chains of the multidrug-resistant tuberculosis Ch strain, which harbors a unique combination of resistance mutations, we analyzed genomes of 25 isolates from 12 patients with diagnosis during 2006-2022 in Chaco Province, Argentina. Amplification of resistance, high mortality rates, and indications of a wider outbreak raise concerns for surveillance programs.

Proper cholesterol transport is crucial for the functionality of cells. In C . elegans , certain cholesterol derivatives called dafachronic acids (DAs) govern the entry into diapause. In their absence, worms form a developmentally arrested dauer larva. Thus, cholesterol transport to appropriate places for DA biosynthesis warrants the reproductive growth. Recently, we discovered a novel class of glycosphingolipids, PEGCs, required for cholesterol mobilization/transport from internal storage pools. Here, we identify other components involved in this process. We found that strains lacking polyunsaturated fatty acids (PUFAs) undergo increased dauer arrest when grown without cholesterol. This correlates with the depletion of the PUFA-derived endocannabinoids 2-arachidonoyl glycerol and anandamide. Feeding of these endocannabinoids inhibits dauer formation caused by PUFAs deficiency or impaired cholesterol trafficking (e.g. in Niemann-Pick C1 or DAF-7/TGF-β mutants). Moreover, in parallel to PEGCs, endocannabinoids abolish the arrest induced by cholesterol depletion. These findings reveal an unsuspected function of endocannabinoids in cholesterol trafficking regulation.

Abstract Brucellaceae are stealthy pathogens with the ability to survive and replicate in the host in the context of a strong immune response. This capacity relies on several virulence factors that are able to modulate the immune system and in their structural components that have low proinflammatory activities. Lipopolysaccharide (LPS), the main component of the outer membrane, is a central virulence factor of Brucella, and it has been well established that it induces a low inflammatory response. We describe here the identification and characterization of a novel periplasmic protein (RomA) conserved in alpha-proteobacteria, which is involved in the homeostasis of the outer membrane. A mutant in this gene showed several phenotypes, such as membrane defects, altered LPS composition, reduced adhesion, and increased virulence and inflammation. We show that RomA is involved in the synthesis of LPS, probably coordinating part of the biosynthetic complex in the periplasm. Its absence alters the normal synthesis of this macromolecule and affects the homeostasis of the outer membrane, resulting in a strain with a hyperinflammatory phenotype. Our results suggest that the proper synthesis of LPS is central to maximize virulence and minimize inflammation. RomA is a periplasmic small protein of Brucella abortus with no known function and conserved among alpha-proteobacteria. We demonstrate that RomA is involved in the biosynthesis of the lipopolysaccharide and necessary to counterbalance virulence and inflammation.

Trypanosomes can synthesize polyunsaturated fatty acids. Previously, we have shown that they possess stearoyl-CoA desaturase (SCD) and oleate desaturase (OD) to convert stearate (C18) into oleate (C18:1) and linoleate (C18:2), respectively. Here we examine if OD is essential to these parasites. Cultured procyclic (insect-stage) form (PCF) and bloodstream-form (BSF) Trypanosoma brucei cells were treated with 12- and 13-thiastearic acid (12-TS and 13-TS), inhibitors of OD, and the expression of the enzyme was knocked down by RNA interference. The phenotype of these cells was studied. Growth of PCF T. brucei was totally inhibited by 100 µM of 12-TS and 13-TS, with EC(50) values of 40±2 and 30±2 µM, respectively. The BSF was more sensitive, with EC(50) values of 7±3 and 2±1 µM, respectively. This growth phenotype was due to the inhibitory effect of thiastearates on OD and, to a lesser extent, on SCD. The enzyme inhibition caused a drop in total unsaturated fatty-acid level of the cells, with a slight increase in oleate but a drastic decrease in linoleate level, most probably affecting membrane fluidity. After knocking down OD expression in PCF, the linoleate content was notably reduced, whereas that of oleate drastically increased, maintaining the total unsaturated fatty-acid level unchanged. Interestingly, the growth phenotype of the RNAi-induced cells was similar to that found for thiastearate-treated trypanosomes, with the former cells growing twofold slower than the latter ones, indicating that the linoleate content itself and not only fluidity could be essential for normal membrane functionality. A similar deleterious effect was found after RNAi in BSF, even with a mere 8% reduction of OD activity, indicating that its full activity is essential. As OD is essential for trypanosomes and is not present in mammalian cells, it is a promising target for chemotherapy of African trypanosomiasis.

Bacillus subtilis responds to a sudden decrease in temperature by transiently inducing the expression of the des gene encoding for a lipid desaturase, Δ5‐Des, which introduces a double bond into the acyl chain of preexisting membrane phospholipids. This Δ5‐Des‐mediated membrane remodeling is controlled by the cold‐sensor DesK. After cooling, DesK activates the response regulator DesR, which induces transcription of des. We show that inhibition of fatty acid synthesis by the addition of cerulenin, a potent and specific inhibitor of the type II fatty acid synthase, results in increased levels of short‐chain fatty acids (FA) in membrane phospholipids that lead to inhibition of the transmembrane‐input thermal control of DesK. Furthermore, reduction of phospholipid synthesis by conditional inactivation of the PlsC acyltransferase causes significantly elevated incorporation of long‐chain FA and constitutive upregulation of the des gene. Thus, we provide in vivo evidence that the thickness of the hydrophobic core of the lipid bilayer serves as one of the stimulus sensed by the membrane spanning region of DesK. We report that inhibition of fatty acid synthesis in Bacillus subtilis by the antibiotic cerulenin results in increased levels of short fatty acids that lead to inhibition of the transmembrane‐input control of DesK thermosensor.

Key message Transcriptomics- and FAME-GC-MS-assisted apomixis breeding generated Paspalum notatum hybrids with clonal reproduction and increased α-linolenic acid content, offering the potential to enhance livestock product's nutritional quality and reduce methane emissions A low omega-6:omega-3 fatty acid ratio is considered an indicator of the nutritional impact of milk fat on human health. In ruminants, major long-chain fatty acids, such as linoleic acid (18:2, omega-6) and α-linolenic acid (18:3, omega-3), originate from dietary sources and reach the milk via the bloodstream. Since forages are the primary source of long-chain fatty acids for such animals, they are potential targets for improving milk lipid composition. Moreover, a high 18:3 content in their diet is associated with reduced methane emissions during grazing. This work aimed to develop genotypes of the forage grass Paspalum notatum with high leaf 18:3 content and the ability for clonal reproduction via seeds (apomixis). We assembled diploid and polyploid Paspalum notatum leaf transcriptomes and recovered sequences of two metabolism genes associated with the establishment of lipid profiles, namely SUGAR-DEPENDENT 1 ( SDP1 ) and PEROXISOMAL ABC TRANSPORTER 1 ( PXA1 ). Primers were designed to amplify all expressed paralogs in leaves. qPCR was used to analyse SDP1 and PXA1 expression in seven divergent genotypes. Reduced levels of SDP1 and PXA1 were found in the polyploid sexual genotype Q4188. Fatty acid methyl esters/gas chromatography/mass spectrometry (FAME/GC/MS) assays confirmed an increased percentage of 18:3 in this genotype. Crosses between Q4188 and the obligate apomictic pollen donor Q4117 resulted in two apomictic F 1 hybrids (JS9 and JS71) with reduced SDP1 and PXA1 levels, increased 18:3 content, and clonal maternal reproduction. These materials could enhance milk and meat quality while reducing greenhouse gas emissions during grazing.

All cells must increase their volumes in response to biomass growth to maintain intracellular mass density within physiologically permissive bounds. Here, we investigate the regulation of volume growth in the Gram-positive bacterium Bacillus subtilis. To increase volume, bacteria enzymatically expand their cell envelopes and insert new envelope material. First, we demonstrate that cell-volume growth is determined indirectly, by expanding their envelopes in proportion to mass growth, similarly to the Gram-negative Escherichia coli, despite their fundamentally different envelope structures. Next, we studied, which pathways might be responsible for robust surface-to-mass coupling: We found that both peptidoglycan synthesis and membrane synthesis are required for proper surface-to-mass coupling. However, surprisingly, neither pathway is solely rate-limiting, contrary to wide-spread belief, since envelope growth continues at a reduced rate upon complete inhibition of either process. To arrest cell-envelope growth completely, the simultaneous inhibition of both envelope-synthesis processes is required. Thus, we suggest that multiple envelope-synthesis pathways collectively confer an important aspect of volume regulation, the coordination between surface growth, and biomass growth.