Title |
Envelope‑Stress Sensing Mechanism of Rcs and Cpx Signaling Pathways in Gram‑Negative Bacteria |
Author |
Seung‑Hyun Cho1,2*, Kilian Dekoninck1,2,3, and Jean‑Francois Collet1,2 |
Address |
1WELBIO-Walloon Excellence in Life Sciences and Biotechnology, 1200 Brussels, Belgium, 2de Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium, 3Present Address: University of California, Berkeley, CA 94720, USA |
Bibliography |
Journal of Microbiology, 61(3),317-329, 2023,
|
DOI |
10.1007/s12275-023-00030-y
|
Key Words |
Rcs · Cpx · RcsF · NlpE · BAM · BamA · Envelope stress response · Two-component system (TCS) |
Abstract |
The global public health burden of bacterial antimicrobial resistance (AMR) is intensified by Gram-negative bacteria,
which have an additional membrane, the outer membrane (OM), outside of the peptidoglycan (PG) cell wall. Bacterial twocomponent
systems (TCSs) aid in maintaining envelope integrity through a phosphorylation cascade by controlling gene
expression through sensor kinases and response regulators. In Escherichia coli, the major TCSs defending cells from envelope
stress and adaptation are Rcs and Cpx, which are aided by OM lipoproteins RcsF and NlpE as sensors, respectively. In
this review, we focus on these two OM sensors. β-Barrel assembly machinery (BAM) inserts transmembrane OM proteins
(OMPs) into the OM. BAM co-assembles RcsF, the Rcs sensor, with OMPs, forming the RcsF-OMP complex. Researchers
have presented two models for stress sensing in the Rcs pathway. The first model suggests that LPS perturbation stress
disassembles the RcsF-OMP complex, freeing RcsF to activate Rcs. The second model proposes that BAM cannot assemble
RcsF into OMPs when the OM or PG is under specific stresses, and thus, the unassembled RcsF activates Rcs. These two
models may not be mutually exclusive. Here, we evaluate these two models critically in order to elucidate the stress sensing
mechanism. NlpE, the Cpx sensor, has an N-terminal (NTD) and a C-terminal domain (CTD). A defect in lipoprotein trafficking
results in NlpE retention in the inner membrane, provoking the Cpx response. Signaling requires the NlpE NTD, but
not the NlpE CTD; however, OM-anchored NlpE senses adherence to a hydrophobic surface, with the NlpE CTD playing
a key role in this function. |