Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine.
Yifan ZhangGiovanni Gonzalez-GutierrezKatherine A LeggBrenna J C WalshCristian M Pis DiezKatherine A EdmondsDavid P GiedrocPublished in: Nature communications (2022)
L-Ergothioneine (ET), the 2-thioimidazole derivative of trimethylhistidine, is biosynthesized by select fungi and bacteria, notably Mycobacterium tuberculosis, and functions as a scavenger of reactive oxygen species. The extent to which ET broadly functions in bacterial cells unable to synthesize it is unknown. Here we show that spd_1642-1643 in Streptococcus pneumoniae, a Gram-positive respiratory pathogen, encodes an ET uptake ATP-binding cassette (ABC) transporter, designated EgtU. The solute binding domain (SBD) of EgtU, EgtUC, binds ET with high affinity and exquisite specificity in a cleft between the two subdomains, with cation-π interactions engaging the betaine moiety and a network of water molecules that surround the thioimidazole ring. EgtU is highly conserved among known quaternary amine compound-specific transporters and widely distributed in Firmicutes, including the human pathogens Listeria monocytogenes, as BilEB, Enterococcus faecalis and Staphylococcus aureus. ET increases the chemical diversity of the low molecular weight thiol pool in Gram-positive human pathogens and may contribute to antioxidant defenses in the infected host.
Keyphrases
- gram negative
- endothelial cells
- mycobacterium tuberculosis
- staphylococcus aureus
- reactive oxygen species
- listeria monocytogenes
- multidrug resistant
- induced pluripotent stem cells
- induced apoptosis
- pluripotent stem cells
- oxidative stress
- small molecule
- transcription factor
- antimicrobial resistance
- binding protein
- high throughput
- dna binding
- candida albicans
- escherichia coli
- biofilm formation
- cell proliferation
- methicillin resistant staphylococcus aureus
- water soluble
- innate immune