7Z8E

Crystal structure of the substrate-binding protein YejA from S. meliloti in complex with peptide fragment

7Z8E の概要

• エントリーDOI: 10.2210/pdb7z8e/pdb
• 分子名称: ABC transporter substrate-binding protein, GLY-SER-ASP-VAL-ALA, SER-SER, ... (7 entities in total)
• 機能のキーワード: peptide transporter, transport protein
• 由来する生物種: Sinorhizobium meliloti; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 70784.44

構造登録者

Morera, S.,Vigouroux, V.,Travin, D.Y. (登録日: 2022-03-17, 公開日: 2023-02-22, 最終更新日: 2024-02-07)

主引用文献

Travin, D.Y.,Jouan, R.,Vigouroux, A.,Inaba-Inoue, S.,Lachat, J.,Haq, F.,Timchenko, T.,Sutormin, D.,Dubiley, S.,Beis, K.,Morera, S.,Severinov, K.,Mergaert, P.
Dual-Uptake Mode of the Antibiotic Phazolicin Prevents Resistance Acquisition by Gram-Negative Bacteria.
Mbio, 14:e0021723-e0021723, 2023

PubMed Abstract: Phazolicin (PHZ) is a peptide antibiotic exhibiting narrow-spectrum activity against rhizobia closely related to its producer, sp. strain Pop5. Here, we show that the frequency of spontaneous PHZ-resistant mutants in Sinorhizobium meliloti is below the detection limit. We find that PHZ can enter S. meliloti cells through two distinct promiscuous peptide transporters, BacA and YejABEF, which belong to the SLiPT (SbmA-like peptide transporter) and ABC (ATP-binding cassette) transporter families, respectively. The dual-uptake mode explains the lack of observed resistance acquisition because the simultaneous inactivation of both transporters is necessary for resistance to PHZ. Since both BacA and YejABEF are essential for the development of functional symbiosis of S. meliloti with leguminous plants, the unlikely acquisition of PHZ resistance via the inactivation of these transporters is further disfavored. A whole-genome transposon sequencing screen did not reveal additional genes that can provide strong PHZ resistance when inactivated. However, it was found that the capsular polysaccharide KPS, the novel putative envelope polysaccharide PPP (PHZ-protecting polysaccharide), as well as the peptidoglycan layer jointly contribute to the sensitivity of S. meliloti to PHZ, most likely serving as barriers that reduce the amount of PHZ transported inside the cell. Many bacteria produce antimicrobial peptides to eliminate competitors and create an exclusive niche. These peptides act either by membrane disruption or by inhibiting essential intracellular processes. The Achilles' heel of the latter type of antimicrobials is their dependence on transporters to enter susceptible cells. Transporter inactivation results in resistance. Here, we show that a rhizobial ribosome-targeting peptide, phazolicin (PHZ), uses two different transporters, BacA and YejABEF, to enter the cells of a symbiotic bacterium, Sinorhizobium meliloti. This dual-entry mode dramatically reduces the probability of the appearance of PHZ-resistant mutants. Since these transporters are also crucial for S. meliloti symbiotic associations with host plants, their inactivation in natural settings is strongly disfavored, making PHZ an attractive lead for the development of biocontrol agents for agriculture.

PubMed: 36802165
DOI: 10.1128/mbio.00217-23

実験手法

X-RAY DIFFRACTION (1.58 Å)