Insights into the Distribution and Functions of the Eukaryotic GPI-like Anchored Genes Among Mycobacterium from a Comparative Genomic Perspective

Glycosylphosphatidylinositol (GPI)-anchored proteins range from small peptides to larger antigens and fulfill a variety of cellular functions in eukaryotes. We speculated there should be such molecules in intracellular pathogens such as Mycobacterium due to their complex interplay with the host. However, no prior publications have touched this topic. To explore the existence and distribution of GPI-like molecules among Mycobacterium, we exhaustively analyzed all publicly available Mycobacterium genomes and found that the GPI-like signal sequences are prevalent among Mycobacterium, and a significant dichotomy between nonpathogenic Mycobacterium (exemplified by Mycobacterium smegmatis) and pathogenic Mycobacterium (exemplified by Mycobacterium tuberculosis), through genome-wide GPI-SOM analysis. Some well-documented anti-tuberculosis drug targets are predicted to have GPI-like anchored signals, such as KasA and atpE. Interestingly, Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins predicted to have GPI-anchoring sequence are unique to pathogenic Mycobacterium. These results can be further explored for better control measures against tuberculosis.