Essential Role of the ESX-5 Secretion System in Outer Membrane Permeability of Pathogenic Mycobacteria.

摘要: Mycobacteria possess different type VII secretion (T7S) systems to secrete proteins across their unusual cell envelope. One of these systems, ESX-5, is only present in slow-growing mycobacteria and responsible for the multiple substrates. However, role ESX-5 substrates growth and/or virulence largely unknown. In this study, we show that esx-5 essential both Mycobacterium marinum bovis. Remarkably, essentiality can be rescued by increasing permeability outer membrane, either altering its lipid composition or introduction heterologous porin MspA. Mutagenesis first nucleotide-binding domain membrane ATPase EccC5 prevented ESX-5-dependent bacterial growth, but did not affect complex assembly. This suggests rescuing effect due pores formed complex, caused activity. Subsequent proteomic analysis identify crucial confirmed all detectable PE PPE surface envelope fractions were routed through ESX-5. Additionally, saturated transposon-directed insertion-site sequencing (TraDIS) was applied wild-type M. cells expressing mspA genes are anymore presence importance esx-5, could substrates, indicating together essentiality. Finally, examination phenotypes on defined carbon sources revealed an mutant strongly impaired uptake utilization hydrophobic sources. Based data, propose a model which system transport required nutrient uptake. These might way compensate lack MspA-like porins mycobacteria.