The inner membrane protein lipopolysaccharide assembly
protein B (LapB) is an adaptor protein that activates the proteolysis
of LpxC by an essential inner membrane metalloprotease,
FtsH, leading to a decrease in the level of lipopolysaccharide
in the membrane. In this study, we revealed the
mechanism by which the essential inner membrane protein
YejM regulates LapB and analyzed the role of the transmembrane
domain of LapB in Escherichia coli. The transmembrane
domain of YejM genetically and physically interacted with
LapB and inhibited its function, which led to the accumulation
of LpxC. The transmembrane domain of LapB was indispensable
for both its physical interaction with YejM and
its regulation of LpxC proteolysis. Notably, we found that the
lapB mutant exhibited strong cold sensitivity and this phenotype
was not associated with increased accumulation of LpxC.
The transmembrane domain of LapB was also required for
its role in adaptation to cold stress. Taken together, these results showed that LapB plays an important role in both
the regulation of LpxC level, which is controlled by its interaction
with the transmembrane domain of YejM, and adaptation
to cold stress, which is independent of LpxC.
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Trypanosoma cruzi is an obligate intracellular parasite transmitted
to vertebrate hosts by blood-sucking insects. Molecules
present in parasites and mammalian cells allow the recognition
and parasite internalization. Metallic ions play an essential
role in the establishment and maintenance of hostparasite
interaction. However, little is known about how parasites
handle with essential and nonessential metal quotas.
This study aimed to investigate the influence of metal ions
on the biological processes of T. cruzi infected cells. Infected
cells were incubated with ZnCl2, CdCl2, and HgCl2 for 12 h
and labeled with different specific dyes to investigate the cellular
events related to intracellular parasite death and elimination.
Infected host cells and parasite’s mitochondria underwent
functional and structural disorders, in addition to
parasite’s DNA condensation and pH decrease on host cells,
which led to parasite death. Further investigations suggested
that lysosomes were involved in pH decrease and the double
membrane of the endoplasmic reticulum formed vacuoles
surrounding damaged parasites, which indicate the occurrence
of autophagy for parasite elimination. In conclusion,
low concentrations of nonessential and essential metals cause
a series of damage to Trypanosoma cruzi organelles, leading
to its loss of viability, death, and elimination, with no removal
of the host cells.
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