YSM Issue 94.2

Microbiology / Chemistry
NEWS
A CURIOUS
SALMONELLA
PROTEIN
SOPD’S STIMULATION AND INHIBITION OF
INFLAMMATION
BY CHRISTOPHER YE
IMAGE COURTESY OF NIAID
The bacterial pathogen Salmonella typhimurium causes
intestinal inflammation. S. typhimurium injects effector
proteins such as SopD that stimulate a signaling cascade,
ultimately leading to inflammation. However, researchers from Yale
and Shandong University discovered that SopD is bifunctional and
can alternatively stimulate or inhibit inflammation. “It contains the
‘Yin and Yang’ elements of the Salmonella/host interaction within
the same protein… a remarkable piece of evolution,” said Jorge
Galán, lead researcher of the study and chair of the Department of
Microbial Pathogenesis at Yale School of Medicine.
“[Inflammation is] essential for [S. typhimurium] to colonize
the intestinal tract, since it allows Salmonella to [compete] with
the resident microbiota and secure nutrients that are otherwise
not accessible in the uninflamed intestine,” Galán said. Rab8
is a regulatory protein that is central for an anti-inflammatory
signaling pathway that helps the host recover homeostasis after
inflammation. Therefore, by inhibiting Rab8, SopD stimulates
inflammation and helps the pathogen replicate within the intestine.
When the researchers solved the SopD-Rab8 complex’s crystal
structure, they identified SopD’s unexpected second function: SopD
can activate Rab8 and stimulate an anti-inflammatory response. In
other words, opposing enzymatic activities are present within the
same protein. Rab8 normally binds to GDI2, an inhibitor that blocks
Rab8 activity. However, SopD can displace GDI2 to activate Rab8 and
inhibit inflammation. By doing so, S. typhimurium sacrifices virulence
to preserve host stability, maximizing its ability to continue replicating.
“[This research is] providing major insight into the pathogenesis
of chronic intestinal inflammatory diseases such as Crohn’s disease,”
Galán said. Understanding Salmonella has implications in the
development of novel therapeutic strategies. ■
Lian, H., Jiang, K., Tong, M. et al. The Salmonella effector protein
SopD targets Rab8 to positively and negatively modulate the
inflammatory response. Nat Microbiol (2021). https://doi.
org/10.1038/s41564-021-00866-3
www.yalescientific.org
“LIKE-DISSOLVES-
LIKE”
UPDATING THEORIES ON
MISCIBILITY
BY VERONICA BROOKS
IMAGE COURTESY OF WIKIMEDIA COMMONS
Miscibility, or the ability for liquids to mix, is often
determined by the “like-dissolves-like” rule, which is
largely qualitative. It remains difficult to quantitatively
determine how “alike” two substances are. But by using the
dielectric constant, Bilin Zhuang, an assistant professor at Yale-
NUS, developed a model that accurately predicts the miscibility
of two liquids using their permanent dipole moments, which
arise from differences in electronegativity across a molecule.
The dielectric constant is a number assigned to a substance
based on how polarized it becomes in an electric field. A molecule
with a high dielectric constant has higher polarity and a greater
ability to stabilize charges in an electric field. Materials with
similar dielectric constants often mix well. Zhuang’s model also
uses the free energy of mixing to predict miscibility of two liquids.
This model accurately fits experimental data when compared to
previous theories that use a similar number of parameters.
However, these new equations are unable to account for
hydrogen bonding, which leads certain liquids to adopt
conformations that the dielectric constant does not predict.
Zhuang’s next steps will focus on developing miscibility
predictors for hydrogen bonding liquids and polarizable
liquids, substances with no permanent dipoles.
Ultimately, these new equations will be particularly
useful for predicting the miscibility of newly synthesized
molecules. It also saves time at the bench when one studies
multi-component mixtures. “We can just plug in the number
and roughly see what the dielectric constant is [and] its
miscibility,” Zhuang said. ■
Zhuang, B., Ramanauskaite, G., Koa, Z. Y., & Wang, Z.-G. (2021).
Like dissolves like: A first-principles theory for predicting liquid
miscibility and mixture dielectric constant. Science Advances,
7(7), 1–7. https://doi.org/10.1126/sciadv.abe7275
May 2021 Yale Scientific Magazine 7