Phylogeny to function: PE/PPE protein evolution and impact on Mycobacterium tuberculosis pathogenicity.
The pe/ppe genes represent one of the most intriguing aspects of the Mycobacterium tuberculosis genome. These genes are especially abundant in pathogenic mycobacteria, with more than 160 members in M. tuberculosis. Despite being discovered over 15 years ago, their function remains unclear, although various lines of evidence implicate selected family members in mycobacterial virulence. In this review, we use PE/PPE phylogeny as a framework within which we examine the diversity and putative functions of these proteins. We report on the evolution and diversity of the respective gene families, as well as the implications thereof for function and host immune recognition. We summarize recent findings on pe/ppe gene regulation, also placing this in the context of PE/PPE phylogeny. We collate data from several large proteomics datasets, providing an overview of PE/PPE localization, and discuss the implications this may have for host responses. Assessment of the current knowledge of PE/PPE diversity suggests that these proteins are not variable antigens as has been so widely speculated; however, they do clearly play important roles in virulence. Viewing the growing body of pe/ppe literature through the lens of phylogeny reveals trends in features and function that may be associated with the evolution of mycobacterial pathogenicity.
Harvard School of Public Health, Boston, MA, USA.|DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
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Fishbein
DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
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van Wyk
DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
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Warren
DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
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Sampson
D000818:Animals; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019143:Evolution, Molecular; D006168:Guinea Pigs; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D005810:Multigene Family; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D010802:Phylogeny; D014774:Virulence / Q000235:genetics
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008565:Membrane Proteins; C440642:PE-PGRS protein, Mycobacterium; C418242:PPE14 protein, Mycobacterium tuberculosis; C582018:PPE2 protein, Mycobacterium tuberculosis