Abstract: The present invention provides methods of putatively identifying, based on presence of rare codon usage, cellular components involved in virulence. Also included are methods of verifying putative virulence genes and methods of attenuating such virulence, e.g., through identification and modification of genes/gene products that modulate translation of gene subsets involved in pathogen virulence. The methods include examining the codon usage and frequency employed in the organism, and identifying and structurally characterizing, e.g., tRNA molecules associated with over-represented or under-represented codons. By targeting the cell's ability to decode specific sets of genes, the virulence of a pathogen can be modulated.