Large-scale survey for potentially targetable indels in bacterial and protozoan proteins.
Our previous results demonstrated that some essential, housekeeping proteins from pathogenic microorganisms may contain sizable insertions-deletions in their sequences (compared to close human homologs) that can be responsible for unexpected virulence properties. For example, we found that indel-bearing elongation factor-1alpha from several pathogenic protozoa can activate a human tyrosine phosphatase SHP-1 leading to deactivation of macrophages. On the one hand, these findings allowed development of a strategy for targeting some indel-containing pathogen proteins that have similar human counterparts. On the other hand, the results raised numerous questions regarding the nature and implications of sequence indels in pathogen proteins. In the present study, we conducted a large-scale survey of indels in proteins from 136 bacterial and protozoan genomes. It has been established that sizable insertions and deletions occur in approximately 5-10% of bacterial proteins with close human homologs, while proteins from the protozoan pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Leishmania donovani exhibit elevated indel content that can reach up to 25%. The finding suggested that the occurrence of sequence indels may be involved in the evolution of pathogenic mechanisms in these protozoa.
Cherkasov
Artem
A
Division of Infectious Diseases, Department of Medicine, University of British Columbia, Faculty of Medicine, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada. artc@interchange.ubc.ca
Lee
Shang-Jung
SJ
Nandan
Devki
D
Reiner
Neil E
NE
D000818:Animals; D001419:Bacteria / Q000472:pathogenicity; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D056890:Eukaryota / Q000472:pathogenicity; D005787:Gene Frequency; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics
D001426:Bacterial Proteins; D009687:Nuclear Proteins; D015800:Protozoan Proteins; D014157:Transcription Factors