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Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence

2016; National Academy of Sciences; Volume: 113; Issue: 3 Linguagem: Inglês

10.1073/pnas.1523321113

1091-6490

JoAnn M. Tufariello, Jessica R. Chapman, Christopher A. Kerantzas, Ka‐Wing Wong, Catherine Vilchèze, Christopher M. Jones, Laura E. Cole, Emir Tinaztepe, Victor Thompson, David Fenyö, Michael Niederweis, Beatrix Ueberheide, Jennifer A. Philips, William R. Jacobs,

Diagnosis and treatment of tuberculosis

Significance Mycobacterium tuberculosis (Mtb) uses type VII secretion systems to secrete cognate protein pairs that alter host interactions. Here, we address the contributions of the ESX-3 secretion system to Mtb growth and pathogenesis through a combination of genetics, proteomics, and growth studies both in vitro and in vivo. ESX-3 is demonstrated to play a critical role in iron acquisition through secretion of a pair pf proteins belonging to the PE–PPE family (PE5–PPE4). In vivo, the importance of PE5–PPE4 secretion was found to depend upon host genotype, likely reflecting a host capacity to restrict iron availability. However, secreted effectors EsxG–EsxH play an iron-independent role in Mtb virulence. Therefore, ESX-3 secretes multiple effectors that target distinct host pathways to influence pathogenesis.