In this format, broad-spectrum antibiotics carry the risk of significant side-effects due to targeting mutualistic bacterial flora. An alternative approach which attempts to avoid the issues surrounding broad-spectrum antibiotics is to select targets from the group of genes identified only by the GCS. These genes are highly conserved throughout the order Rickettsiales but have little similarity to essential genes in other bacteria.

While it is quite possible that these wBm genes have orthologs throughout the bacterial kingdom, the experimental data available in DEG suggests that they would not be essential for the growth of bacteria in general. Druggability was predicted by identifying wBm proteins with sequence similarity to the targets of small molecule drugs. However, an intriguing secondary application RG7112 ic50 exists. Comparison

of wBm proteins to drug targeted proteins additionally produces a list of approved drug and drug-like compounds which bind proteins of similar sequences to wBm proteins. Protein sequence similarity does not guarantee identical BYL719 cost structures or binding pockets, thus it is unlikely that a single turn-key compound will be identified through target similarity. However, it seems reasonable that careful filtering of this set could reveal a panel of potential binding compounds primed for optimization and derivatization using traditional medicinal chemistry. This opens the interesting possibility of applying bioinformatic PD-0332991 concentration analysis to bypass a portion of the arduous de novo drug development pipeline. Conclusion Through this analysis we were able to predict genes important for the survival of a biologically intractable organism using two complementary bioinformatic techniques. These predictions can then be used as a tool to facilitate the selection of genes to enter into the drug development process against this organism. Comparison of the two predictions revealed Edoxaban that different but overlapping sets of genes were predicted,

stemming from the approaches applied. By MHS, 253 genes were predicted as having a high likelihood of being essential. All but 8 of those genes were also identified by the second method, GCS. An additional 299 genes were also identified by GCS alone as highly conserved in Wolbachia’s parent order Rickettsiales. Overall, 552 wBm genes, approximately 69% of the genome, were identified as having a high confidence in a prediction of essentiality. The overlapping and uniquely identified sets of genes can facilitate alternative approaches for drug target selection. Methods BLAST against DEG The 805 Refseq protein sequences for the Wolbachia endosymbiont of B. malayi strain TRS were downloaded from the NCBI ftp site ftp://​ftp.​ncbi.​nlm.​nih.​gov/​genomes/​Bacteria. The Database of Essential Genes (DEG) version 5.2 was provided by Dr. Ren Zhang at the Centre of BioInformatics, Tianjin University.