Regulation of LPS assembly via controlled proteolysis and sensing of LPS stress in Escherichia coli - Publikacja - MOST Wiedzy

Wyszukiwarka

Regulation of LPS assembly via controlled proteolysis and sensing of LPS stress in Escherichia coli

Abstrakt

Lipopolysaccharide (LPS) is a complex glycolipid, essential for the bacterial viability and along with phospholipids, it constitutes the major amphiphilic component of outer membrane (OM) in most of the Gram-negative bacteria, including Escherichia coli. LPS molecules confer an effective permeability barrier to the OM and play a crucial role in bacteria-environment and -host interactions. The synthesis and accumulation of this highly heterogeneous in the composition molecule are controlled by abundance of regulatory factors and growth conditions. Furthermore, the synthesis of LPS and phospholipids is tightly co-regulated and held at a nearly constant ratio. Any alterations in the balance of phospholipids and LPS are not tolerated by bacteria and cause cell death. This balance is achieved by tightly regulated turnover of unstable LpxC enzyme to maintain the flux of common precursor for the utilization in either LPS or phospholipid biosynthetic pathways. It constitutes an essential branch point in the biosynthesis of phospholipids and the lipid A part of LPS and simultaneously determines the first committed step in LPS biosynthetic pathway. It has been reported that LPS assembly requires the essential LapB protein to regulate FtsH-mediated proteolysis of LpxC protein. To further understand the function of LapB and its role in LpxC turnover, multicopy suppressor screening of ΔlapB was employed and it revealed a role for HslUV proteases in regulating LpxC amounts, providing the first alternative pathway of LpxC degradation. Isolation and characterization of an extragenic suppressor mutation that prevents lethality of ΔlapB by restoration of normal LPS synthesis identified a frame-shift in the essential gene designated lapC, suggesting LapB and LapC act antagonistically. The same lapC gene was identified during selection for mutations that induce transcription from LPS defects-responsive rpoEP3 promoter, confer sensitivity to LpxC inhibitor CHIR090 and exhibit a temperature-sensitive phenotype. Suppressors of lapC mutants that restored growth at elevated temperatures mapped to lapA/lapB, lpxC and ftsH genes. Such suppressor mutations restored normal levels of LPS and prevented excessive proteolysis of LpxC in lapC mutants. Interestingly, a lapC deletion could be constructed in strains either overproducing LpxC or in the absence of LapB, revealing that FtsH, LapB and LapC together regulate LPS synthesis by controlling LpxC amounts.

Cytuj jako

Pełna treść

pobierz publikację
pobrano 88 razy
Wersja publikacji
Accepted albo Published Version
Licencja
Copyright (Author(s))

Słowa kluczowe

Informacje szczegółowe

Kategoria:
Doktoraty, rozprawy habilitacyjne, nostryfikacje
Typ:
praca doktorska pracowników zatrudnionych w PG oraz studentów studium doktoranckiego
Język:
angielski
Rok wydania:
2022
Weryfikacja:
Politechnika Gdańska

wyświetlono 125 razy

Publikacje, które mogą cię zainteresować

Meta Tagi