TY - JOUR
T1 - Metabolomics Assay Identified a Novel Virulence-Associated Siderophore Encoded by the High-Pathogenicity Island in Uropathogenic Escherichia coli
AU - Xu, Guang
AU - Guo, Hao
AU - Lv, Haitao
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China grants (Nos. 81274175 and 31670031), National Key R&D Program of China (No. 2017YFC1308600), and the Startup Funding for Specialized Professorship provided by Shanghai Jiao Tong University (No. WF220441502). Authors give thanks to Dr. Tian Tian in the Chongqing University for scientific discussion.
Publisher Copyright:
© Copyright 2019 American Chemical Society.
PY - 2019/5
Y1 - 2019/5
N2 - To date, yersiniabactin remains the only identified
siderophore encoded by the high pathogenicity island (HPI) in uropathogenic Escherichia coli (UPEC).
In the present study, we aim to discover and identify new siderophores in the
HPI-dependent biosynthetic pathway using a combinational strategy of
metabolomics and genetics. A global metabolome assay of wild-type UTI89,
UTI89ΔybtS, and UTI89ΔybtS with the substrate addition of salicylic acid found
numerous unknown metabolite features that were encoded by the HPI with an
obvious substrate dependency on salicylic acid. One metabolite feature with m/z 307.0206 was shown to have a similar phenotype as
yersiniabactin. Furthermore, isotope mass spectrum calculations and MS/MS
annotations were combined to identify this metabolite as HPTzTn-COOH.
HPTzTn-COOH was verified as a new siderophore in this study, and it was
observed to have a robust capacity to chelate different metals, including Al3+, Ni2+,
and Ca2+, in addition to binding Fe3+. Our data revealed that HPTzTn-COOH has a
stronger diagnostic ability over the more conventionally used yersiniabactin,
as characterized by its high production throughout UPEC strains harboring HPI.
Altogether, our discoveries revise the siderophore family, and HPTzTn-COOH can
be classified as an additional key siderophore along with yersiniabactin.
AB - To date, yersiniabactin remains the only identified
siderophore encoded by the high pathogenicity island (HPI) in uropathogenic Escherichia coli (UPEC).
In the present study, we aim to discover and identify new siderophores in the
HPI-dependent biosynthetic pathway using a combinational strategy of
metabolomics and genetics. A global metabolome assay of wild-type UTI89,
UTI89ΔybtS, and UTI89ΔybtS with the substrate addition of salicylic acid found
numerous unknown metabolite features that were encoded by the HPI with an
obvious substrate dependency on salicylic acid. One metabolite feature with m/z 307.0206 was shown to have a similar phenotype as
yersiniabactin. Furthermore, isotope mass spectrum calculations and MS/MS
annotations were combined to identify this metabolite as HPTzTn-COOH.
HPTzTn-COOH was verified as a new siderophore in this study, and it was
observed to have a robust capacity to chelate different metals, including Al3+, Ni2+,
and Ca2+, in addition to binding Fe3+. Our data revealed that HPTzTn-COOH has a
stronger diagnostic ability over the more conventionally used yersiniabactin,
as characterized by its high production throughout UPEC strains harboring HPI.
Altogether, our discoveries revise the siderophore family, and HPTzTn-COOH can
be classified as an additional key siderophore along with yersiniabactin.
KW - metabolomics
KW - siderophore
KW - pathogenic E. coli
KW - drug target
UR - http://www.scopus.com/inward/record.url?scp=85065188356&partnerID=8YFLogxK
U2 - 10.1021/acs.jproteome.9b00190
DO - 10.1021/acs.jproteome.9b00190
M3 - Journal article
C2 - 30994357
AN - SCOPUS:85065188356
SN - 1535-3893
VL - 18
SP - 2331
EP - 2336
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 5
ER -