Bacterial Lipoproteins Shift Cellular Metabolism to Glycolysis in Macrophages Causing Bone Erosion

Nguyen, Minh-Thu; Hu, Zhicheng; Mohammad, Majd; Schöttler, Hannah; Niemann, Silke; Schultz, Michelle; Barczyk-Kahlert, Katarzyna; Jin, Tao; Hayen, Heiko; Herrmann, Mathias

doi:10.1128/spectrum.04293-22

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…Importantly, staphylococcal lipoproteins can trigger a shift toward fermentative metabolism in bone marrow-derived macrophages. Specifically, di-acylated lipoproteins more profoundly drive the metabolic shift in leukocytes, leading to increased joint inflammation and bone destruction in vivo , affirming the hypothesized connection between bacterial lipoprotein exposure, macrophage metabolic changes, and subsequent bone damage ( Nguyen et al, 2023 ). Staphylococcus aureus peptidoglycan has been demonstrated to possess significant arthritogenic properties.…”

Section: To Study the Role Of Bacterial Virulence Factors In Septic A...mentioning

confidence: 72%

Exploring the role of bacterial virulence factors and host elements in septic arthritis: insights from animal models for innovative therapies

Jin

2024

Front. Microbiol.

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Septic arthritis, characterized as one of the most aggressive joint diseases, is primarily attributed to Staphylococcus aureus (S. aureus) and often results from hematogenous dissemination. Even with prompt treatment, septic arthritis frequently inflicts irreversible joint damage, leading to sustained joint dysfunction in a significant proportion of patients. Despite the unsatisfactory outcomes, current therapeutic approaches for septic arthritis have remained stagnant for decades. In the clinical context, devising innovative strategies to mitigate joint damage necessitates a profound comprehension of the pivotal disease mechanisms. This entails unraveling how bacterial virulence factors interact with host elements to facilitate bacterial invasion into the joint and identifying the principal drivers of joint damage. Leveraging animal models of septic arthritis emerges as a potent tool to achieve these objectives. This review provides a comprehensive overview of the historical evolution and recent advancements in septic arthritis models. Additionally, we address practical considerations regarding experimental protocols. Furthermore, we delve into the utility of these animal models, such as their contribution to the discovery of novel bacterial virulence factors and host elements that play pivotal roles in the initiation and progression of septic arthritis. Finally, we summarize the latest developments in novel therapeutic strategies against septic arthritis, leveraging insights gained from these unique animal models.

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Section: To Study the Role Of Bacterial Virulence Factors In Septic A...mentioning

confidence: 72%

Exploring the role of bacterial virulence factors and host elements in septic arthritis: insights from animal models for innovative therapies

Jin

2024

Front. Microbiol.

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“…LPPs, a group of membrane proteins of S. aureus , are a major regulator of macrophage immune responses and metabolism, with di-acylated lipopeptides in LPPs showing the most significant effect. 7 Molecular docking was performed to investigate the possible interaction of mTOR and Pam2csk4, a synthetic analogue of di-acylated lipopeptides. The dimerized mTOR and the most favored binding sites were shown ( Figure 3D ).…”

Section: Resultsmentioning

confidence: 99%

“… 5 , 6 Macrophages are important innate immune cells and serve as the first line of defense against pathogenic infections through phagocytosis and chemokine secretion, in addition to the role played by skin barrier. 7 However, bacterial lipoproteins (LPPs) in Gram-positive bacteria, particularly S. aureus , can induce multiple distinct cellular states in macrophages, and these inflammatory trajectories change as the infection persists. 6 , 8 These characteristics bring about significant complexities in researches and treatments.…”

Section: Introductionmentioning

confidence: 99%

Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages

Yu,

Zheng,

et al. 2023

JIR

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Purpose This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus ( S. aureus ) pneumonia and clarify its possible mechanism. Methods We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms were investigated: the mTOR-RPS6 pathway phosphorylation and phagocytosis. Furthermore, for the mechanism verification in vivo, mice with specific Mtor knockout in myeloid cells were constructed for pneumonia models. Results Rapa exacerbated S. aureus pneumonia in mouse models, promoting chemokines secretion and inflammatory cells infiltration in lung. In vitro, Rapa upregulated the secretion of chemokines and cytokines in macrophages induced by S. aureus . Mechanistically, the mTOR-ribosomal protein S6 (RPS6) pathway in macrophages was phosphorylated in response to S. aureus infection, and the inhibition of RPS6 phosphorylation upregulated the inflammation level. However, Rapa did not increase the phagocytic activity. Accordingly, mice with specific Mtor knockout in myeloid cells experienced more severe S. aureus pneumonia. Conclusion Rapa exacerbates S. aureus pneumonia by increasing the inflammatory levels of macrophages. Inhibition of mTOR-RPS6 pathway upregulates the expression of cytokines and chemokines in macrophages, thus increases inflammatory cells infiltration and exacerbates tissue damage.

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The immune cells in modulating osteoclast formation and bone metabolism

Hong,

Luo,

et al. 2024

International Immunopharmacology

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Bacterial Lipoproteins Shift Cellular Metabolism to Glycolysis in Macrophages Causing Bone Erosion

Cited by 5 publications

References 54 publications

Exploring the role of bacterial virulence factors and host elements in septic arthritis: insights from animal models for innovative therapies

Exploring the role of bacterial virulence factors and host elements in septic arthritis: insights from animal models for innovative therapies

Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages

The immune cells in modulating osteoclast formation and bone metabolism

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