RT Journal Article
SR Electronic
T1 WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 297440
DO 10.1101/297440
A1 Abdallah M. Abdallah
A1 E.M. Weerdenburg
A1 Qingtian Guan
A1 R. Ummels
A1 S. Borggreve
A1 S.A. Adroub
A1 Tareq B. Malas
A1 Raeece Naeem
A1 Huoming Zhang
A1 T.D. Otto
A1 W. Bitter
A1 A. Pain
YR 2018
UL http://biorxiv.org/content/early/2018/05/02/297440.abstract
AB The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.