Development and validation
of the targeted MS Esx-1 secretion assay.
(A) nLC–MRM analysis of EsxA. Relative EsxA levels within the
cell lysate (CL, blue bars) or in the culture filtrate (CF, red bars)
generated from Esx-1-deficient strains as compared to wild-type M. marinum. (B) nLC–MRM analysis of EsxB. For EsxA
and EsxB, the ΔRD1, ΔesxA, and ΔesxBA strains served as negative controls for EsxA and EsxB
detection and demonstrated the specificity of the approach. (C) nLC–MRM
analysis of the levels of the EspB substrate in the CL and CF relative
to the levels of EspB in the wild-type strain. For EspB, the espB::Tn strain served as a negative control for EspB detection
and demonstrated the specificity of the approach. (D) nLC–MRM
analysis of the levels of the EspF substrate in the CL and CF. (E)
nLC–MRM analysis of MMAR_2929. (F) nLC–MRM analysis
of EsxN. Error bars represent the average propagated standard error
and were calculated as described in the Experimental
Procedures. In all graphs changes in the levels of protein
in each of the Esx-1-deficient strains as compared to the wild-type
strain were considered significantly different from each other if
the p value from a two-tailed Student’s t test was ≤0.05. Changes in protein levels between
the wild-type and each Esx-1-deficient strain that were not statistically
significant (p ≥ 0.05) were as follows: (A)
The levels of EsxA in the cell lysates from the espI, eccD1, espJ, and espK strains were not statistically different from the levels
in the wild-type strain. (B) The levels of EsxB in the cell lysates
from the eccD1, espJ,
and espK strains were not statistically different
from the levels in the wild-type strain. (C) The levels of EspB in
the cell lysates from the eccB1-2, eccCb, esxBA, esxA, eccD1, espK, and espL were not significantly different from the levels in the wild-type
strain. (F) The levels of EsxN in the lysates from the ΔRD1, espG1, eccB1-2, espI, eccD1, espJ, espK, espL, and espB strains were not statistically different from the wild-type strain.
The levels of EsxN in the culture filtrate generated from the eccCb, eccD1, and espJ strains were not statistically different from the WT strain. The
actual p values are listed in the Supporting Information (Table S2). Log2 transformed
versions of the CF data are available in Supplemental
Figure S4.