PPE38 modulates the innate immune response and is required for Mycobacterium marinum virulence.
The proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) family proteins are prevalent in pathogenic mycobacteria and play a diverse role in mycobacterial pathogenesis. While some members have been studied, the function of most PE/PPE proteins remains unknown. In this study, we isolated a transposon-inactivated PPE38 mutant of Mycobacterium marinum and characterized its phenotype. We found that the PPE38 protein is associated with the cell wall and exposed on the cell surface. The inactivation of PPE38 altered the bacterial cell surface properties and led to deficiencies in cord formation, sliding motility, and biofilm formation. The PPE38 mutant was defective in phagocytosis by macrophages and exhibited reduced virulence in adult zebrafish. We also found that PPE38 is involved in the induction of proinflammatory cytokines in infected macrophages. Together, our results indicate that PPE38, a previously uncharacterized protein, plays a role in mycobacterial virulence, presumably by modulating the host innate immune response.
Key Laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.
Dandan
D
Dong
Decheng
D
Wang
Ming
M
Li
Hui
H
Wang
Jia
J
Yu
Chuan
C
Wang
Jun
J
Liu
Qian
Q
Gao
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004251:DNA Transposable Elements; D017353:Gene Deletion; D057131:Immune Evasion; D007113:Immunity, Innate / Q000187:drug effects*; D008124:Locomotion; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D016254:Mutagenesis, Insertional; D019910:Mycobacterium marinum / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D010587:Phagocytosis; D013499:Surface Properties; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015027:Zebrafish
D000942:Antigens, Bacterial; D016207:Cytokines; D004251:DNA Transposable Elements; D037521:Virulence Factors