POSTERS - BLAST X - University of Utah
POSTERS - BLAST X - University of Utah
POSTERS - BLAST X - University of Utah
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<strong>BLAST</strong> X Tue. Evening Session<br />
SYNTHETIC LETHALITY UNCOVERS A NOVEL LINK BETWEEN THE MalT AND OmpR<br />
REGULONS<br />
Sylvia A. Reimann and Alan J. Wolfe<br />
Loyola <strong>University</strong> Chicago, Maywood, Il<br />
Synthetic lethality (SL) is a genetic term for the inviability <strong>of</strong> a double mutant combination<br />
<strong>of</strong> two fully viable single mutants. SL is commonly interpreted as redundancy at an essential<br />
metabolic step. However, a second, less well-known, class <strong>of</strong> SL exists: the so-called “defectdamage-repair”<br />
(DDR) cycles that link apparently unrelated metabolic pathways (Ting et al.,<br />
2008).<br />
We have isolated an SL mutant <strong>of</strong> the form ompR SL(ompR), where SL(ompR) refers to<br />
a mutation that causes death when present in a cell that lacks the two-component response<br />
regulator OmpR. This global regulator is required for proper assembly <strong>of</strong> the cell envelope and<br />
we reasoned that the nature <strong>of</strong> the SL(ompR) mutation would provide further insight into the role<br />
<strong>of</strong> OmpR and its regulon.<br />
Using a combined genetic/genomic approach, we mapped the SL(ompR) mutation to<br />
malT, which encodes the transcription factor MalT. Because overexpression <strong>of</strong> the MalT<br />
inhibitor MalK did not rescue growth, we proposed that the malT mutation leads to a<br />
constitutively active form (MalT c ). To test this hypothesis, we deleted the MalT-dependent lamB,<br />
which encodes an outer membrane porin, and found that this deletion suppressed the SL <strong>of</strong> the<br />
ompR malT c mutant.<br />
Since LamB and OmpR do not perform redundant functions, we propose that the<br />
observed SL is <strong>of</strong> the DDR variety, as follows: the defect (MalT c activity) leads to damage<br />
(constitutive expression <strong>of</strong> LamB) that is repaired by one or more members <strong>of</strong> the OmpR<br />
regulon. To further understand the role <strong>of</strong> OmpR, we are currently seeking OmpR regulon<br />
members that can suppress the SL <strong>of</strong> the ompR malT c mutant.<br />
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