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Staphylococcus warneri is a coagulase-negative staphylococcus that is a normal inhabitant of the skin. It is also considered to be an opportunistic etiological agent causing significant infections in human and animals. Currently, relatively little attention has been paid to the genome biology of S. warneri pathogenicity and antibiotic resistance, which are emerging issues for this etiological agent with considerably clinical significance. In this study, we determined the complete genome sequence of S. warneri strain GD01 recovered from the sampled muscle abscess tissue of a diseased pig in South China. The genome of S. warneri is composed of a circular chromosome of 2,473,911 base pairs as well as eight plasmid sequences. Genome-wide metabolic reconstruction revealed 82 intact functional modules driving the catabolism of respiration and fermentation for energy production, uptake of distinct sugars as well as two-component regulatory systems. The evidence uncovered herein enables better understanding for metabolic potential and physiological traits of this etiological agent. The antibiotic susceptibility test demonstrated that S. warneri GD01 was resistant to penicillin, amoxicillin, ampicillin, cefalexin, vancomycin, and sulfisoxazole. The associations between antibiotic phenotypes and the related genotypes were identified to reveal the molecular basis conferring resistance to this pathogen. A number of genes coding for potential virulence factors were firstly depicted in the genome of S. warneri GD01, including adhesins, exoenzymes, capsule, and iron acquisition proteins. Our study provides a valuable genomic context of the genes/modules devoting to metabolism, antibiotic resistance, and virulence of S. warneri.

Despite the fact that ADP-ribosylation of eukaryotic elongation factor 2 (EF2) leads to inhibition of protein synthesis, the mechanism by which ADP-ribosylated EF2 (ADPR•EF2) causes this inhibition remains controversial. Here, we applied modeling approaches to investigate the consequences of various modes of ADPR•EF2 inhibitory actions on the two coupled processes, the polypeptide chain elongation and ADP-ribosylation of EF2. Modeling of experimental data indicates that ADPR•EF2 fully blocks the late-phase translocation of tRNAs; but the impairment in the translocation upstream process, mainly the GTP-dependent factor binding with the pretranslocation ribosome and/or the guanine nucleotide exchange in EF2, is responsible for the overall inhibition kinetics. The reduced ADPR•EF2-ribosome association spares the ribosome to bind and shield native EF2 against toxin attack, thereby deferring the inhibition of protein synthesis inhibition and inactivation of EF2. Minimum association with the ribosome also keeps ADPR•EF2 in an accessible state for toxins to catalyze the reverse reaction when nicotinamide becomes available. Our work underscores the importance of unveiling the interactions between ADPR•EF2 and the ribosome, and argues against that toxins inhibit protein synthesis through converting native EF2 to a competitive inhibitor to actively disable the ribosome.