Taurine-Mediated IDOL Contributes to Resolution of Streptococcus uberis Infection

Abstract

Metabolic alterations occur in pathogen infections, but the role of lipid metabolism in the progression of bacterial mastitis is unclear. Crosstalk between lipid droplets (LDs) and invading bacteria occurs and targeting of de novo lipogenesis inhibits pathogen reproduction. Herein, we investigate the role(s) of lipid metabolism in mammary cells during Streptococcus uberis (S. uberis) infection. Our results indicate that S. uberis induces the synthesis of fatty acids and production of LDs. Importantly, taurine reduces fatty acid synthesis, the abundance of LDs and the in vitro bacterial load of S. uberis. These changes are mediated, at least partly, by the E3 ubiquitin ligase IDOL, which is associated with the degradation of low-density lipoprotein receptors (LDLRs). We have identified a critical role for IDOL-mediated fatty acid synthesis in bacterial infection, and suggest that taurine may be an effective prophylactic or therapeutic strategy for preventing S. uberis mastitis.

Formononetin Protects LPS-Induced Mastitis Through Suppressing Inflammation and Enhancing Blood-Milk Barrier Integrity via AhR-Induced Src Inactivation

“…Inflammation was involved in the development of mastitis (17). The invading bacteria could activate the innate immune system and lead to the production of inflammatory and oxidative mediators (18). These increased inflammatory mediators such as TNF-a, IL-1ß and IL-6 contributed to the pathogenesis of mastitis (19).…”

FABP4-mediated lipid droplet formation in Streptococcus uberis-infected macrophages supports host defence

“…LD formation occurs during the infection of macrophages with numerous intracellular pathogens, including S. uberis. A previous study in our laboratory found that S. uberis specifically induces LD formation as a pathogenic strategy to create a depot of host lipids for use as a carbon source to fuel intracellular bacterial growth in mammary epithelial cells [18]. Herein, we show that LD formation is not a bacterially driven process during S. uberis infection but rather occurs as a result of immune activation of macrophages as part of a host defence mechanism.…”

“…The level of LDs is closely related to lipid metabolism. Previous results in our laboratory have shown that S. uberis infection changes fatty acid synthesis pathways in mammary epithelial cells [18] and in mice [28]. We sought to confirm whether the bacteria have a similar effect on macrophages.…”

“…Dias et al indicated that LDs have important functions in the modulation of inflammatory mediator production in SARS-CoV-2-infected monocytes [17]. Our laboratory previously found that S. uberis infection significantly increases LDs in mammary epithelial cells, and these LDs appear to support pathogen infection [18]. Macrophages are the most consequential immune cells in mammary tissue, and the effect of LD levels on pathogen invasion and their specific mechanisms are unclear.…”

“…After infection with S. uberis for 3 h at mid-exponential phase (OD 600 = 0.4-0.6), S. uberis-infected cells were washed 3 times (15 min at 37 °C each time) with PBS containing 100 mg/mL gentamicin, followed by gentamicinfree PBS. Cells were pelleted at 1.4 g for 10 min, both cells and the supernatant were collected, equal numbers of cells were lysed with sterile triple distilled water, and CFUs were counted by the spread plate method after incubation for 12 h at 37 °C [18].…”