Compounds targeting YadC of uropathogenic Escherichia coli and its host receptor annexin A2 decrease bacterial colonization in bladder

Xiao, Li; Pei, Geng; Zhang, Lisong; Cao, Yang; Wang, Jingyu; Lu, Yu; Wei, Dianjun; Gao, Shan; Zhang, Zhisong; Yao, Zhi; Wang, Quan

doi:10.1016/j.ebiom.2019.11.014

Cited by 13 publications

(9 citation statements)

References 52 publications

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“…On the other hand, during the pathophysiology of sepsis, Anxa2 −/− mice showed increased production of pro-inflammatory IL-17 and reactive oxygen species, increased neutrophil infiltration, but reduced bacterial clearance and animal survival [ 190 ]. While these studies rather implicate intracellular AnxA2 functions, during the adhesion and invasion of uropathogenic Escherichia coli to bladder epithelial cells, AnxA2 was identified as the receptor of the bacterial protein YadC, which participates in binding to bladder epithelial cells [ 191 ]. Inhibition of AnxA2 using the Ca 2+ -chelator BAPTA-AM or compound A-05, which inhibits the AnxA2/p11 complex [ 192 ], attenuated E.coli infection in vivo [ 191 ].…”

Section: Anxa2mentioning

confidence: 99%

“…While these studies rather implicate intracellular AnxA2 functions, during the adhesion and invasion of uropathogenic Escherichia coli to bladder epithelial cells, AnxA2 was identified as the receptor of the bacterial protein YadC, which participates in binding to bladder epithelial cells [ 191 ]. Inhibition of AnxA2 using the Ca 2+ -chelator BAPTA-AM or compound A-05, which inhibits the AnxA2/p11 complex [ 192 ], attenuated E.coli infection in vivo [ 191 ]. Likewise, AnxA2 on the surface of vascular endothelial cells served as a docking site for Rickettsia , with AnxA2 deficiency blocking Rickettsia adherence to the luminal surface of blood vessels in vivo [ 193 ] ( Table 2 f).…”

Section: Anxa2mentioning

confidence: 99%

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Annexin Animal Models—From Fundamental Principles to Translational Research

Grewal

Rentero

Enrich

et al. 2021

IJMS

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Routine manipulation of the mouse genome has become a landmark in biomedical research. Traits that are only associated with advanced developmental stages can now be investigated within a living organism, and the in vivo analysis of corresponding phenotypes and functions advances the translation into the clinical setting. The annexins, a family of closely related calcium (Ca2+)- and lipid-binding proteins, are found at various intra- and extracellular locations, and interact with a broad range of membrane lipids and proteins. Their impacts on cellular functions has been extensively assessed in vitro, yet annexin-deficient mouse models generally develop normally and do not display obvious phenotypes. Only in recent years, studies examining genetically modified annexin mouse models which were exposed to stress conditions mimicking human disease often revealed striking phenotypes. This review is the first comprehensive overview of annexin-related research using animal models and their exciting future use for relevant issues in biology and experimental medicine.

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Section: Anxa2mentioning

confidence: 99%

Section: Anxa2mentioning

confidence: 99%

Annexin Animal Models—From Fundamental Principles to Translational Research

Grewal

Rentero

Enrich

et al. 2021

IJMS

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“…To explore the potential cause of the disparity of lipidomic profiles in these coculture systems including neutrophils, bacterial survival was assessed. Previous studies have shown that CFT073 E. coli is capable of adhesion, invasion, and colonization in epithelial cells and resistance to neutrophil killing mechanisms ( Li et al, 2019 ) ( Amunugama et al, 2021b ). Thus, we tested the hypothesis that CFT073 E. coli survival is greater in the presence of neutrophils compared to that of JM109 E. coli .…”

Section: Resultsmentioning

confidence: 99%

E. coli strain-dependent lipid alterations in cocultures with endothelial cells and neutrophils modeling sepsis

2022

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Dysregulated lipid metabolism is common in infection and inflammation and is a part of the complex milieu underlying the pathophysiological sequelae of disease. Sepsis is a major cause of mortality and morbidity in the world and is characterized by an exaggerated host response to an infection. Metabolic changes, including alterations in lipid metabolism, likely are important in sepsis pathophysiology. Here, we designed an in vitro cell culture model using endothelial cells, E. coli, and neutrophils to mimic sepsis in a simplified cell model. Lipid alterations were studied in the presence of the pathogenic E. coli strain CFT073 and non-pathogenic E. coli strain JM109. We employed untargeted lipidomics to first identify lipid changes and then targeted lipidomics to confirm changes. Both unique and shared lipid signatures were identified in cocultures with these E. coli strains. In the absence of neutrophils, the CFT073 strain elicited alterations in lysophosphatidylcholine and diglyceride molecular species during coculture while both strains led to increases in phosphatidylglycerols. Lipid alterations in these cocultures changed with the addition of neutrophils. In the presence of neutrophils with E. coli and endothelial cells, triglyceride increases were a unique response to the CFT073 strain while phosphatidylglycerol and diglyceride increases occurred in response to both strains. Phosphatidylethanolamine also increased in neutrophils, E. coli and endothelial cells cocultures, and this response was greater in the presence of the CFT073 strain. We further evaluated changes in phosphatidylethanolamine in a rat model of sepsis, which showed multiple plasma phosphatidylethanolamine molecular species were elevated shortly after the induction of sepsis. Collectively, these findings demonstrate unique lipid responses by co-cultures of E. coli with endothelial cells which are dependent on the E. coli strain as well as the presence of neutrophils. Furthermore, increases in phosphatidylethanolamine levels in CFT073 urosepsis E. coli, endothelial cell, neutrophil cocultures were similarly observed in the plasma of septic rats.

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“…The extraintestinal pathogenic Escherichia coli (ExPEC) strain, CFT073, was grown in 20 ml M9 minimal medium for 48 h at 37˚C [29]. Following washing, E coli was added at 15 MOI relative to the macrophages [29,79]. B. burgdorferi RNA was prepared as described previously [33] and used at a dosage of 2 μg/ml.…”

Section: Cell Culturementioning

confidence: 99%

The Cdkn2a gene product p19 alternative reading frame (p19ARF) is a critical regulator of IFNβ-mediated Lyme arthritis

Paquette

et al. 2022

PLoS Pathog

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Type I interferon (IFN) has been identified in patients with Lyme disease, and its abundant expression in joint tissues of C3H mice precedes development of Lyme arthritis. Forward genetics using C3H mice with severe Lyme arthritis and C57BL/6 (B6) mice with mild Lyme arthritis identified the Borrelia burgdorferi arthritis-associated locus 1 (Bbaa1) on chromosome 4 (Chr4) as a regulator of B. burgdorferi-induced IFNβ expression and Lyme arthritis severity. B6 mice introgressed with the C3H allele for Bbaa1 (B6.C3-Bbaa1 mice) displayed increased severity of arthritis, which is initiated by myeloid lineage cells in joints. Using advanced congenic lines, the physical size of the Bbaa1 interval has been reduced to 2 Mbp, allowing for identification of potential genetic regulators. Small interfering RNA (siRNA)-mediated silencing identified Cdkn2a as the gene responsible for Bbaa1 allele-regulated induction of IFNβ and IFN-stimulated genes (ISGs) in bone marrow-derived macrophages (BMDMs). The Cdkn2a-encoded p19 alternative reading frame (p19ARF) protein regulates IFNβ induction in BMDMs as shown by siRNA silencing and overexpression of ARF. In vivo studies demonstrated that p19ARF contributes to joint-specific induction of IFNβ and arthritis severity in B. burgdorferi-infected mice. p19ARF regulates B. burgdorferi-induced IFNβ in BMDMs by stabilizing the tumor suppressor p53 and sequestering the transcriptional repressor BCL6. Our findings link p19ARF regulation of p53 and BCL6 to the severity of IFNβ-induced Lyme arthritis in vivo and indicate potential novel roles for p19ARF, p53, and BCL6 in Lyme disease and other IFN hyperproduction syndromes.

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Compounds targeting YadC of uropathogenic Escherichia coli and its host receptor annexin A2 decrease bacterial colonization in bladder

Cited by 13 publications

References 52 publications

Annexin Animal Models—From Fundamental Principles to Translational Research

Annexin Animal Models—From Fundamental Principles to Translational Research

E. coli strain-dependent lipid alterations in cocultures with endothelial cells and neutrophils modeling sepsis

The Cdkn2a gene product p19 alternative reading frame (p19ARF) is a critical regulator of IFNβ-mediated Lyme arthritis

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