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Phosphorylation of CFP10 modulates Mycobacterium tuberculosis virulence

ABSTRACT: Virulence effectors secreted by Mycobacterium tuberculosis (Mtb) help subvert host immune mechanisms and, therefore, are critical for establishing infection and pathogenesis. However, knowledge in terms of signaling mechanisms that modulate the secretion of virulence factors is sparse. We performed high-throughput secretome, phosphoproteome, and phospho-secretome analysis of Mtb. We combined the analysis with empirical validations to show regulation of mycobacterial secretion through protein phosphorylation. System level PPI network analysis superimposed with the secretome, phosphoproteome, and phospho-secretome profile revealed an intricate relationship between phosphorylation and secretion. At the core of the network was a key virulence factor CFP10. We identified PknA to be the kinase responsible for phosphorylating CFP10. Using genetic tools, we show that phosphomimetic mutation of CFP10 negatively regulates the secretion of virulence mediator ESAT6. Significantly, the dynamics of CFP10 phosphorylation strongly influenced bacterial virulence and survival within macrophages and mice. Together, the results show that the dynamic phosphorylation status of the secretory protein CFP10 regulates the secretion of virulence factors and impacts virulence.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mycobacterium Tuberculosis H37rv

SUBMITTER: Vinay Kumar Nandicoori

LAB HEAD: Vinay kumar

PROVIDER: PXD045586 | Pride | 2023-09-22

REPOSITORIES: Pride

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			Action	DRS
	ESC-Expl-2-column-2-micron-40deg-25cm-C6-ACETONE-90min-16-01-23-Priyadharshini.msf	Msf
	ESC-Expl-2-column-2-micron-40deg-25cm-C6-ACETONE-90min-16-01-23-Priyadharshini.raw	Raw
	ESC-Expl-2-column-2-micron-40deg-25cm-CF1-90min-16-01-23-Priyadharshini.msf	Msf
	ESC-Expl-2-column-2-micron-40deg-25cm-CF1-90min-16-01-23-Priyadharshini.raw	Raw
	ESC-Expl-2-column-2-micron-40deg-25cm-CF2-90min-16-01-23-Priyadharshini.msf	Msf

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Phosphorylation of CFP10 modulates Mycobacterium tuberculosis virulence

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