Hyperglycemia Increases Severity of Staphylococcus aureus Osteomyelitis and Influences Bacterial Genes Required for Survival in Bone

Butrico, Casey E.; Klopfenstein, Nathan; Green, Erin R; Johnson, Joshua; Peck, Sun H.; Ibberson, Carolyn B.; Serezani, Carlos Henrique; Cassat, James E.

doi:10.1128/iai.00529-22

Cited by 7 publications

(2 citation statements)

References 70 publications

(112 reference statements)

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“…In this study, high glucose greatly reduced the pigment formation and cytotoxicity of S. aureus when grown in LB medium, which was restored by the addition of sodium pyruvate, but this phenomenon was not observed in the CDM medium. High glucose has been shown to reduce the production of virulence factors by S. aureus in vitro ( Regassa et al, 1992 ; Seidl et al, 2008 ; Dufresne et al, 2022 ), but hyperglycemia makes individuals more susceptible to developing severe S. aureus infection ( Thurlow et al, 2020 ; Butrico et al, 2023 ). These data indicate that pyruvate may be involved in the pathogenic process of S. aureus induced diabetic foot infections.…”

Section: Discussionmentioning

confidence: 99%

Role of sodium pyruvate in maintaining the survival and cytotoxicity of Staphylococcus aureus under high glucose conditions

Chen

Yao

et al. 2023

Front. Microbiol.

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Glucose is a crucial carbon source for the growth of Staphylococcus aureus, but an excess of glucose is detrimental and even leads to cell death. Pyruvate, the central metabolite of glycolysis, has been shown to have anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effect of pyruvate on S. aureus under high glucose conditions. Sodium pyruvate greatly increased the cytotoxicity of S. aureus strain BAA-1717 to human erythrocytes and neutrophils in vitro. However, the cytotoxicity and survival of S. aureus were significantly reduced by high glucose, which was restored to normal levels by the addition of sodium pyruvate. The expression of hlg and lukS in S. aureus was higher in the LB-GP cultures than that in LB-G cultures, but there was no significant difference in cytotoxicity between LB-GP and LB-G cultures. Furthermore, the hemolytic activity of S. aureus supernatants could be inhibited by the cell-free culture medium (CFCM) of LB-G cultures, suggesting that high levels of extracellular proteases were presence in the CFCM of LB-G cultures, resulting in degradation of the hemolytic factors. The expression of sarA, which negatively regulates extracellular protease secretion, was higher in LB-GP cultures than that in LB-G cultures. Additionally, sodium pyruvate increased acetate production in S. aureus, which helps maintain cell viability under acidic environment. In conclusion, pyruvate plays an important role in the survival and cytotoxicity of S. aureus under high glucose conditions. This finding may aid in the development of effective treatments for diabetic foot infections.

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Section: Discussionmentioning

confidence: 99%

Role of sodium pyruvate in maintaining the survival and cytotoxicity of Staphylococcus aureus under high glucose conditions

Chen

Yao

et al. 2023

Front. Microbiol.

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“…This is also observed in mouse models, where S. aureus skin infection was more severe in diabetic mice and correlated with diminished ROS production, PMN activation, and impaired humoral responses compared to nondiabetic mice [ 181 , 182 ]. S. aureus burden and infection severity were also significantly increased in abscesses and osteomyelitis following streptozotocin-induced hyperglycemia [ 183 , 184 ]. Collectively, these findings support the fact that S. aureus thrives in a glucose-rich environment, which is known to induce a wide array of virulence factors that can augment host tissue damage and leukocyte dysfunction [ 183 , 185 , 186 ].…”

Section: Potential Metabolic Targets To Modulate S Aureus ...mentioning

confidence: 99%

Metabolism Shapes Immune Responses to <i>Staphylococcus aureus</i>

Arumugam,

Kielian

2023

J Innate Immun

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Staphylococcus aureus (S. aureus) is a common cause of hospital- and community-acquired infections that can result in various clinical manifestations ranging from mild to severe disease. The bacterium utilizes different combinations of virulence factors and biofilm formation to establish a successful infection, and the emergence of methicillin- and vancomycin-resistant strains introduces additional challenges for infection management and treatment. Metabolic programming of immune cells regulates the balance of energy requirements for activation and dictates pro- vs. anti-inflammatory function. Recent investigations into metabolic adaptations of leukocytes and S. aureus during infection indicate that metabolic crosstalk plays a crucial role in pathogenesis. Furthermore, S. aureus can modify its metabolic profile to fit an array of niches for commensal or invasive growth. Here we focus on the current understanding of immunometabolism during S. aureus infection and explore how metabolic crosstalk between the host and S. aureus influences disease outcome. We also discuss how key metabolic pathways influence leukocyte responses to other bacterial pathogens when information for S. aureus is not available. A better understanding of how S. aureus and leukocytes adapt their metabolic profiles in distinct tissue niches may reveal novel therapeutic targets to prevent or control invasive infections.

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Reactive Oxygen‐Correlated Photothermal Imaging of Smart COF Nanoreactors for Monitoring Chemodynamic Sterilization and Promoting Wound Healing

Zhu,

Feng,

Chen

et al. 2024

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Chemodynamic therapy (CDT) has emerged as a promising approach for treating infected diabetic wounds, while reliable imaging technology for simultaneous monitoring of ROS and therapeutic processes is still a formidable challenge. Herein, smart covalent organic framework (COF) nanoreactors (COF NRs) are constructed by hyaluronic acid (HA) packaged glucose oxidase (GOx) covalently linked Fe‐COF for diabetic wound healing. Upon the breakdown of the HA protective layer, GOx consumes glucose to produce gluconic acid and hydrogen peroxide (H2O2), resulting in decreased local pH and H2O2 supplementation. Density functional theory (DFT) calculations show that Fe‐COF has high catalytic activity towards H2O2, leading to in situ generation of hydroxyl radicals (·OH) for sterilization, and the localized downregulation of glucose effectively improved the microenvironment of diabetic wounds. Meanwhile, based on the near‐infrared photothermal imaging of oxidized 3,3′,5,5′‐tetramethylbenzidine (oxTMB), the authors showed that TMB can be applied for the point‐of‐care testing of ·OH and glucose, and assessing the sterilization progress in vivo. More significantly, the facile photothermal signaling strategy can be extended to monitor various ROS‐mediated therapeutic systems, enabling accurate prediction of treatment outcomes.

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Hyperglycemia Increases Severity of Staphylococcus aureus Osteomyelitis and Influences Bacterial Genes Required for Survival in Bone

Cited by 7 publications

References 70 publications

Role of sodium pyruvate in maintaining the survival and cytotoxicity of Staphylococcus aureus under high glucose conditions

Role of sodium pyruvate in maintaining the survival and cytotoxicity of Staphylococcus aureus under high glucose conditions

Metabolism Shapes Immune Responses to <i>Staphylococcus aureus</i>

Reactive Oxygen‐Correlated Photothermal Imaging of Smart COF Nanoreactors for Monitoring Chemodynamic Sterilization and Promoting Wound Healing

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