Emergence and Modular Evolution of a Novel Motility Machinery in Bacteria

Bacteria glide across solid surfaces by mechanisms that have remained largely mysterious despite decades of research. In the deltaproteobacterium Myxococcus xanthus, this locomotion allows the formation stress-resistant fruiting bodies where sporulation takes place. However, despite the large number of genes identified as important for gliding, no specific machinery has been identified so far, hampering in-depth investigations. Based on the premise that components of the gliding machinery must have co-evolved and encode both envelope-spanning proteins and a molecular motor, we re-annotated known gliding motility genes and examined their taxonomic distribution, genomic localization, and phylogeny. We successfully delineated three functionally related genetic clusters, which we proved experimentally carry genes encoding the basal gliding machinery in M. xanthus, using genetic and localization techniques. For the first time, this study identifies structural gliding motility genes in the Myxobacteria and opens new perspectives to study the motility mechanism. Furthermore, phylogenomics provide insight into how this machinery emerged from an ancestral conserved core of genes of unknown function that evolved to gliding by the recruitment of functional modules in Myxococcales. Surprisingly, this motility machinery appears to be highly related to a sporulation system, underscoring unsuspected common mechanisms in these apparently distinct morphogenic phenomena

RNAi Screening Implicates a SKN-1-Dependent Transcriptional Response in Stress Resistance and Longevity Deriving from Translation Inhibition

Caenorhabditis elegans SKN-1 (ortholog of mammalian Nrf1/2/3) is critical for oxidative stress resistance and promotes longevity under reduced insulin/IGF-1-like signaling (IIS), dietary restriction (DR), and normal conditions. SKN-1 inducibly activates genes involved in detoxification, protein homeostasis, and other functions in response to stress. Here we used genome-scale RNA interference (RNAi) screening to identify mechanisms that prevent inappropriate SKN-1 target gene expression under non-stressed conditions. We identified 41 genes for which knockdown leads to activation of a SKN-1 target gene (gcs-1) through skn-1-dependent or other mechanisms. These genes correspond to multiple cellular processes, including mRNA translation. Inhibition of translation is known to increase longevity and stress resistance and may be important for DR-induced lifespan extension. One model postulates that these effects derive from reduced energy needs, but various observations suggest that specific longevity pathways are involved. Here we show that translation initiation factor RNAi robustly induces SKN-1 target gene transcription and confers skn-1-dependent oxidative stress resistance. The accompanying increases in longevity are mediated largely through the activities of SKN-1 and the transcription factor DAF-16 (FOXO), which is required for longevity that derives from reduced IIS. Our results indicate that the SKN-1 detoxification gene network monitors various metabolic and regulatory processes. Interference with one of these processes, translation initiation, leads to a transcriptional response whereby SKN-1 promotes stress resistance and functions together with DAF-16 to extend lifespan. This stress response may be beneficial for coping with situations that are associated with reduced protein synthesis

Effect of Turmerin on Endothelial Denudation by Air Drying

The objective of this study is to determine if arterial endothelial injury can be attenuated by local application of 80 μg/ml turmerin at the site of injury and by oral administration of the same dose. Anesthetized Lewis rats (n =12) weighing 200 ± 4.0 gms randomly were assigned to two groups. After 5 min of air drying a segment of right carotid artery, six rats were treated locally 80μg/ml with turmerin and the rest were treated with 0.9% NaCl. Turmerin was then administered by gavage (80 μg) every 24 hrs for 14 days. Animals were sacrificed on day 14 and the carotid artery removed from the injured site for histological analysis and serum collected for lipid peroxidation analysis by measuring malondialdehyde (MDA) and conjugated dienes. This study showed no proliferation in the intima of one rat out of six rats treated with turmerin while there was significant variation between the treated rats and the controls. MDA for control was 0.593±0.02 nanomoles/ml while turmerin was 0.187±0.04 (p≤0.01); conjugated diene for control was 0.402±0.03 nanomoles/ml while turmerin was 0.212±0.04 nanomoles/ml (p ≤0.05). Although there was significant reduction in serum peroxidation activity, the histological findings indicate that attenuation of carotid artery injury may involve other factors than decreased lipid peroxidation