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Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis
Published on: May 23, 2021
Transcriptomic analysis reveals that the small protein MgtS contributes to the virulence of uropathogenic Escherichia
Shujie Li1, Yu Pang1, Si Zhang1
1Tianjin Key Laboratory of Microbial Functional Genomics, TEDA College, Nankai University, Tianjin, 300457, China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, 300457, China.
Abstract:
Uropathogenic Escherichia coli (UPEC) is the most common pathogen causing urinary tract infections (UTIs). The pathogenesis of UPEC relies on the formation of intracellular bacterial communities (IBCs) after invading bladder epithelial cells (BECs). In this study, the gene expression profiles of UPEC after invading BECs were comprehensively analyzed using RNA sequencing to reveal potential virulence-related genes. The small protein MgtS, which is transcriptionally upregulated in BECs, was further investigated. It was found that MgtS contributed positively to UPEC invasion of BECs and colonization in murine bladders. A two-component regulatory system, PhoPQ was confirmed as a direct activator of mgtS expression in BECs, and magnesium limitation is proposed as a host cue for the activation. This study provides the first comprehensive analysis of the transcriptome profile of UPEC during its intra-BECs life, revealing a new virulence-associated gene and its regulatory mechanism.
Insights
Uropathogenic Escherichia coli (UPEC) uses the small protein MgtS to invade bladder cells and colonize during urinary tract infections (UTIs). The PhoPQ system regulates MgtS, activated by magnesium limitation within host cells.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Uropathogenic Escherichia coli (UPEC) is a primary cause of urinary tract infections (UTIs).
- UPEC pathogenesis involves forming intracellular bacterial communities (IBCs) within bladder epithelial cells (BECs).
Purpose of the Study:
- To comprehensively analyze UPEC gene expression within BECs using RNA sequencing.
- To identify novel virulence factors and regulatory mechanisms involved in UPEC's intracellular lifestyle.
Main Methods:
- RNA sequencing to profile UPEC gene expression after BEC invasion.
- Investigating the role of the small protein MgtS in UPEC virulence.
- Confirming the regulatory role of the PhoPQ two-component system on mgtS expression.
Main Results:
- Identified MgtS as a small protein upregulated in BECs, positively impacting UPEC invasion and bladder colonization.
- Confirmed PhoPQ as a direct activator of mgtS expression in BECs.
- Proposed magnesium limitation as a host-derived cue activating the PhoPQ-mgtS pathway.
Conclusions:
- This study offers the first comprehensive transcriptomic analysis of UPEC within BECs.
- Revealed MgtS as a novel virulence-associated gene in UPEC pathogenesis.
- Elucidated a new regulatory mechanism involving PhoPQ and magnesium limitation for UPEC virulence in UTIs.
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