Unravelling the lipoyl‐relay of exogenous lipoate utilization in Bacillus subtilis

Lipoate is an essential cofactor for key enzymes of oxidative and one-carbon metabolism. It is covalently attached to E2 subunits of dehydrogenase complexes and GcvH, the H subunit of the glycine cleavage system. Bacillus subtilis possess two protein lipoylation pathways: biosynthesis and scavenging. The former requires octanoylation of GcvH, insertion of sulfur atoms and amidotransfer of the lipoate to E2s, catalyzed by LipL. Lipoate scavenging is mediated by a lipoyl protein ligase (LplJ) that catalyzes a classical two-step ATP-dependent reaction. Although these pathways were thought to be redundant, a ∆lipL mutant, in which the endogenous lipoylation pathway of E2 subunits is blocked, showed growth defects in minimal media even when supplemented with lipoate and despite the presence of a functional LplJ. In this study, we demonstrate that LipL is essential to modify E2 subunits of branched chain ketoacid and pyruvate dehydrogenases during lipoate scavenging. The crucial role of LipL during lipoate utilization relies on the strict substrate specificity of LplJ, determined by charge complementarity between the ligase and the lipoylable subunits. This new lipoyl-relay required for lipoate scavenging highlights the relevance of the amidotransferase as a valid target for the design of new antimicrobial agents among Gram-positive pathogens.Fil: Rasetto, Natalí Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Lavatelli, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Martin, Natalia. Michigan State University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Mansilla, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

A Precise Measurement of the Weak Mixing Angle in Neutrino-Nucleon Scattering

We report a precise measurement of the weak mixing angle from the ratio of neutral current to charged current inclusive cross-sections in deep-inelastic neutrino-nucleon scattering. The data were gathered at the CCFR neutrino detector in the Fermilab quadrupole-triplet neutrino beam, with neutrino energies up to 600 GeV. Using the on-shell definition, ${\rm sin ^2\theta_W} \equiv 1 - \frac{{\rm M_W} ^2}{{\rm M_Z} ^2}$, we obtain ${\rm sin ^2\theta_W} = 0.2218 \pm 0.0025 ({\rm stat.}) \pm 0.0036 ({\rm exp.\: syst.}) \pm 0.0040 ({\rm model})$.Comment: 10 pages, Nevis Preprint #1498 (Submitted to Phys. Rev. Lett.

Determination of the Strange Quark Content of the Nucleon from a Next-to-Leading-Order QCD Analysis of Neutrino Charm Production

We present the first next-to-leading-order QCD analysis of neutrino charm production, using a sample of 6090 $\nu_\mu$- and $\bar\nu_\mu$-induced opposite-sign dimuon events observed in the CCFR detector at the Fermilab Tevatron. We find that the nucleon strange quark content is suppressed with respect to the non-strange sea quarks by a factor \kappa = 0.477 \: ^{+\:0.063}_{-\:0.053}, where the error includes statistical, systematic and QCD scale uncertainties. In contrast to previous leading order analyses, we find that the strange sea $x$-dependence is similar to that of the non-strange sea, and that the measured charm quark mass, $m_c = 1.70 \pm 0.19 \:{\rm GeV/c}^2$, is larger and consistent with that determined in other processes. Further analysis finds that the difference in $x$-distributions between $xs(x)$ and $x\bar s(x)$ is small. A measurement of the Cabibbo-Kobayashi-Maskawa matrix element $|V_{cd}|=0.232 ^{+\:0.018}_{-\:0.020}$ is also presented. uufile containing compressed postscript files of five Figures is appended at the end of the LaTeX source.Comment: Nevis R#150

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Phosphoenolpyruvate carboxylase in Corynebacterium glutamicum is dispensable for growth and lysine production.

Peters-Wendisch P, Eikmanns BJ, Thierbach G, Bachmann B, Sahm H. Phosphoenolpyruvate carboxylase in Corynebacterium glutamicum is dispensable for growth and lysine production. FEMS Microbiology Letters. 1993;112:269-274

Regular cellular distribution of plasmids by oscillating and filament-forming ParA ATPase of plasmid pB171.

Centromere-like loci from bacteria segregate plasmids to progeny cells before cell division. The ParA ATPase (a MinD homologue) of the par2 locus from plasmid pB171 forms oscillating helical structures over the nucleoid. Here we show that par2 distributes plasmid foci regularly along the length of the cell even in cells with many plasmids. In vitro, ParA binds ATP and ADP and has a cooperative ATPase activity. Moreover, ParA forms ATP-dependent filaments and cables, suggesting that ParA can provide the mechanical force for the observed regular distribution of plasmids. ParA and ParB interact with each other in a bacterial two-hybrid assay but do not interact with FtsZ, eight other essential cell division proteins or MreB actin. Based on these observations, we propose a simple model for how oscillating ParA filaments can mediate regular cellular distribution of plasmids. The model functions without the involvement of partition-specific host cell receptors and is thus consistent with the striking observation that partition loci can function in heterologous host organisms