POSTERS - BLAST X - University of Utah

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