Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export

The NS1 protein of influenza virus is a major virulence factor essential for virus replication, as it redirects the host cell to promote viral protein expression. NS1 inhibits cellular messenger ribonucleic acid (mRNA) processing and export, down-regulating host gene expression and enhancing viral gene expression. We report in this paper the identification of a nontoxic quinoline carboxylic acid that reverts the inhibition of mRNA nuclear export by NS1, in the absence or presence of the virus. This quinoline carboxylic acid directly inhibited dihydroorotate dehydrogenase (DHODH), a host enzyme required for de novo pyrimidine biosynthesis, and partially reduced pyrimidine levels. This effect induced NXF1 expression, which promoted mRNA nuclear export in the presence of NS1. The release of NS1-mediated mRNA export block by DHODH inhibition also occurred in the presence of vesicular stomatitis virus M (matrix) protein, another viral inhibitor of mRNA export. This reversal of mRNA export block allowed expression of antiviral factors. Thus, pyrimidines play a necessary role in the inhibition of mRNA nuclear export by virulence factors

MccE Provides Resistance to Protein Synthesis Inhibitor Microcin C by Acetylating the Processed Form of the Antibiotic*

The heptapeptide-nucleotide microcin C (McC) is a potent inhibitor of enteric bacteria growth. McC is excreted from producing cells by the MccC transporter. The residual McC that remains in the producing cell can be processed by cellular aminopeptidases with the release of a non-hydrolyzable aspartyl-adenylate, a strong inhibitor of aspartyl-tRNA synthetase. Accumulation of processed McC inside producing cells should therefore lead to translation inhibition and cessation of growth. Here, we show that a product of another gene of the McC biosynthetic cluster, mccE, acetylates processed McC and converts it into a non-toxic compound. MccE also makes Escherichia coli resistant to albomycin, a Trojan horse inhibitor unrelated to McC that, upon processing, gives rise to a serine coupled to a thioxylofuranosyl pyrimidine, an inhibitor of seryl-tRNA synthetase. We speculate that MccE and related cellular acetyltransferases of the Rim family may detoxify various aminoacyl-nucleotides, either exogenous or those generated inside the cell

Colourful niches of phototrophic microorganisms shaped by vibrations of the water molecule

The photosynthetic pigments of phototrophic microorganisms cover different regions of the solar light spectrum. Utilization of the light spectrum can be interpreted in terms of classical niche theory, as the light spectrum offers opportunities for niche differentiation and allows coexistence of species absorbing different colors of light. However, which spectral niches are available for phototrophic microorganisms? Here, we show that the answer is hidden in the vibrations of the water molecule. Water molecules absorb light at specific wavebands that match the energy required for their stretching and bending vibrations. Although light absorption at these specific wavelengths appears only as subtle shoulders in the absorption spectrum of pure water, these subtle shoulders create large gaps in the underwater light spectrum due to the exponential nature of light attenuation. Model calculations show that the wavebands between these gaps define a series of distinct niches in the underwater light spectrum. Strikingly, these distinct spectral niches match the light absorption spectra of the major photosynthetic pigments. This suggests that vibrations of the water molecule have played