The glycobiology of uropathogenic <i>E. coli</i> infection: the sweet and bitter role of sugars in urinary tract immunity

Lupo, Federico; Ingersoll, Molly A.; Pineda, Miguel A.

doi:10.1111/imm.13330

Cited by 21 publications

(10 citation statements)

References 112 publications

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“…Glycan microarray analysis revealed differences in the ability of rods, LEX rods and LEX filaments to bind to different glycan moieties (Table S1). However, these differences did not appear to involve glycans known to be involved in influencing macrophage engulfment and are not predicted to be a major contributing factor in reduced engulfment of filaments [56].…”

Section: Resultsmentioning

confidence: 99%

The role of bacterial size, shape and surface in macrophage engulfment of uropathogenicE. colicells

Peterson

Söderström

Prins

et al. 2022

Preprint

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Uropathogenic Escherichia coli (UPEC) can undergo extensive filamentation in the host during acute urinary tract infections (UTIs). It has been hypothesised that this morphological plasticity allows bacteria to avoid host immune responses such as macrophage engulfment. However, it is still unclear what properties of filaments are important in macrophage-bacteria interactions. The aim of this work was to investigate the contribution of bacterial biophysical parameters, such as cell size and shape, and physiological parameters, such as cell surface and the environment, to macrophage engulfment efficiency. Viable, reversible filaments of known lengths and volumes were produced in the UPEC strain UTI89 using a variety of methods, including exposure to cell-wall targeting antibiotics, genetic manipulation and isolation from an in vitro human bladder cell model. Quantification of the engulfment ability of macrophages using gentamicin-protection assays and fluorescence microscopy demonstrated that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, surface and external environmental factors. UTI89 filamentation was also found to occur independently of the SOS-inducible filamentation genes, sulA and ymfM, demonstrating the non-essential requirement of these genes for UTI89 filamentation and their ability to avoid macrophage engulfment. With several strains of UPEC now resistant to current antibiotics, our work identifies the importance of bacterial morphology during infection and may provide new ways to prevent or treat these infections via immune modulation or antimicrobials.

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Section: Resultsmentioning

confidence: 99%

The role of bacterial size, shape and surface in macrophage engulfment of uropathogenicE. colicells

Peterson

Söderström

Prins

et al. 2022

Preprint

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“…Several clinical investigations have described the benefits of D-mannose in patients suffering from rUTI (Chiu et al, 2022; Kranjčec et al, 2014; Parazzini et al, 2022). D-mannose is known to bind to UPEC adhesin protein FimH and thus prevent them from adhering to bladder epithelial cells (reviewed in Lupo et al, 2021). However, D-mannose has also been shown to dampen inflammation (Ito et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

D-mannose ameliorates age-associated cellular senescence in the bladder urothelium and NLRP3/Gasdermin/IL-1β -driven pyroptotic epithelial cell shedding

Joshi

Salazar

Wang

et al. 2022

Preprint

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Aging is a risk factor for disease via increased susceptibility to infection, decreased ability to maintain homeostasis, inefficiency in combatting stress, and decreased regenerative capacity. Multiple diseases including urinary tract infection (UTI), are more prevalent with age; however, the mechanisms underlying how aging affects the urinary tract mucosa and the reason why aging correlates with disease are poorly understood. Here, we show that, relative to young (8-12 weeks) mice, the urothelium of aged (18-24 months) female mice accumulates large lysosomes with decreased acid phosphatase activity and shows overall decreased autophagic flux. Aged bladders exhibit basally high accumulation of reactive oxygen species (ROS) and dampened redox response. Furthermore, the aged urothelium exhibits a canonical senescence-associated secretory phenotype (SASP) at baseline with continuous NLRP3-inflammasome- and Gasdermin D (GSDMD)-dependent pyroptotic cell death. Accordingly, we find that aged mice chronically exfoliate epithelial cells. When infected with uropathogenic E. coli, infected aged mice harbor more bacterial reservoirs post-infection and are prone to spontaneous recurrent UTI. Finally, treatment of aged mice with D-Mannose, a natural bioactive monosaccharide, rescues autophagy flux, reverses SASP, and limits pyroptotic epithelial shedding. Thus, normal aging dramatically affects bladder physiology with aging alone increasing baseline cellular stress and susceptibility to infection. Additionally, our results suggest that mannose supplementation could serve as a senotherapeutic to limit age-associated urothelial dysfunction.

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“…It is aware that bacteria being in the wrong place within the body can be quite hazardous. For example, E. coli, as a typical resident in the intestine, can cause infection once entering the urethra (124), abdominal cavity (125), and other regions of the body (126). Due to the in-depth understanding of the interaction between microorganisms and tumors, utilizing specialized bacteria for distinct tumor types can not only avoid infection, but also exert a regulatory influence on the local microecology.…”

Section: Perspectives and Prospectsmentioning

confidence: 99%

Current Status and Future Directions of Bacteria-Based Immunotherapy

Tang

Xian

et al. 2022

Front. Immunol.

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With the in-depth understanding of the anti-cancer immunity, immunotherapy has become a promising cancer treatment after surgery, radiotherapy, and chemotherapy. As natural immunogenicity substances, some bacteria can preferentially colonize and proliferate inside tumor tissues to interact with the host and exert anti-tumor effect. However, further research is hampered by the infection-associated toxicity and their unpredictable behaviors in vivo. Due to modern advances in genetic engineering, synthetic biology, and material science, modifying bacteria to minimize the toxicity and constructing a bacteria-based immunotherapy platform has become a hotspot in recent research. This review will cover the inherent advantages of unedited bacteria, highlight how bacteria can be engineered to provide greater tumor-targeting properties, enhanced immune-modulation effect, and improved safety. Successful applications of engineered bacteria in cancer immunotherapy or as part of the combination therapy are discussed as well as the bacteria based immunotherapy in different cancer types. In the end, we highlight the future directions and potential opportunities of this emerging field.

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The glycobiology of uropathogenic E. coli infection: the sweet and bitter role of sugars in urinary tract immunity

Cited by 21 publications

References 112 publications

The role of bacterial size, shape and surface in macrophage engulfment of uropathogenicE. colicells

The role of bacterial size, shape and surface in macrophage engulfment of uropathogenicE. colicells

D-mannose ameliorates age-associated cellular senescence in the bladder urothelium and NLRP3/Gasdermin/IL-1β -driven pyroptotic epithelial cell shedding

Current Status and Future Directions of Bacteria-Based Immunotherapy

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