Immunization with recombinant protein Ag43::UpaH with alum and 1,25(OH)2D3 adjuvants significantly protects Balb/C mice against urinary tract infection caused by uropathogenic Escherichia coli

Habibi, Mehri; Azimi, Saba; Khoobbakht, Dorna; Roghanian, Pooneh; Karam, Mohammad Reza Asadi

doi:10.1016/j.intimp.2021.107638

Cited by 2 publications

(2 citation statements)

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“…In this study ( Figure 9 ), based on the results of network pharmacology analysis, we screened several pathways related to natural immunity and inflammation, among which TLR4-NFκB was of interest to us. In animal experiments, the Balb/C mouse model is widely used in studies of UTI caused by uropathogenic Escherichia coli ( Shea et al., 2020 ; Habibi et al., 2021 ; Dickson et al., 2023 ). It has been shown to establish persistent intracellular bacterial communities in their urinary epithelial cells ( Chockalingam et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

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Uropathogenic Escherichia coli infection: innate immune disorder, bladder damage, and Tailin Fang II

Li,

et al. 2024

Front. Cell. Infect. Microbiol.

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BackgroundUropathogenic Escherichia coli (UPEC) activates innate immune response upon invading the urinary tract, whereas UPEC can also enter bladder epithelial cells (BECs) through interactions with fusiform vesicles on cell surfaces and subsequently escape from the vesicles into the cytoplasm to establish intracellular bacterial communities, finally evading the host immune system and leading to recurrent urinary tract infection (RUTI). Tailin Fang II (TLF-II) is a Chinese herbal formulation composed of botanicals that has been clinically proven to be effective in treating urinary tract infection (UTI). However, the underlying therapeutic mechanisms remain poorly understood.MethodsNetwork pharmacology analysis of TLF-II was conducted. Female Balb/C mice were transurethrally inoculated with UPEC CFT073 strain to establish the UTI mouse model. Levofloxacin was used as a positive control. Mice were randomly divided into four groups: negative control, UTI, TLF-II, and levofloxacin. Histopathological changes in bladder tissues were assessed by evaluating the bladder organ index and performing hematoxylin-eosin staining. The bacterial load in the bladder tissue and urine sample of mice was quantified. Activation of the TLR4-NF-κB pathway was investigated through immunohistochemistry and western blotting. The urinary levels of interleukin (IL)-1β and IL-6 and urine leukocyte counts were monitored. We also determined the protein expressions of markers associated with fusiform vesicles, Rab27b and Galectin-3, and levels of the phosphate transporter protein SLC20A1. Subsequently, the co-localization of Rab27b and SLC20A1 with CFT073 was examined using confocal fluorescence microscopy.ResultsData of network pharmacology analysis suggested that TLF-II could against UTI through multiple targets and pathways associated with innate immunity and inflammation. Additionally, TLF-II significantly attenuated UPEC-induced bladder injury and reduced the bladder bacterial load. Meanwhile, TLF-II inhibited the expression of TLR4 and NF-κB on BECs and decreased the urine levels of IL-1β and IL-6 and urine leukocyte counts. TLF-II reduced SLC20A1 and Galectin-3 expressions and increased Rab27b expression. The co-localization of SLC20A1 and Rab27b with CFT073 was significantly reduced in the TLF-II group.ConclusionCollectively, innate immunity and bacterial escape from fusiform vesicles play important roles in UPEC-induced bladder infections. Our findings suggest that TLF-II combats UPEC-induced bladder infections by effectively mitigating bladder inflammation and preventing bacterial escape from fusiform vesicles into the cytoplasm. The findings suggest that TLF-II is a promising option for treating UTI and reducing its recurrence.

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Section: Discussionmentioning

confidence: 99%

“…coli (Shea et al, 2020;Habibi et al, 2021;Dickson et al, 2023). It has been shown to establish persistent intracellular bacterial communities in their urinary epithelial cells (Chockalingam et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Uropathogenic Escherichia coli infection: innate immune disorder, bladder damage, and Tailin Fang II

Li,

et al. 2024

Front. Cell. Infect. Microbiol.

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Uropathogenic Escherichia coli endeavors: an insight into the characteristic features, resistance mechanism, and treatment choice

Arafi,

Hasani,

Sadeghi

et al. 2023

Arch Microbiol

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Immunization with recombinant protein Ag43::UpaH with alum and 1,25(OH)2D3 adjuvants significantly protects Balb/C mice against urinary tract infection caused by uropathogenic Escherichia coli

Cited by 2 publications

References 37 publications

Uropathogenic Escherichia coli infection: innate immune disorder, bladder damage, and Tailin Fang II

Uropathogenic Escherichia coli infection: innate immune disorder, bladder damage, and Tailin Fang II

Uropathogenic Escherichia coli endeavors: an insight into the characteristic features, resistance mechanism, and treatment choice

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