Mycobacterium tuberculosis protease Rv3090 is associated with late cell apoptosis and participates in organ injuries and mycobacterial dissemination in mice

Cui, Yingying; Tang, Yangyang; Shao, Mingzhu; Zang, Xinxin; Jiang, Yanyan; Cui, Ziyin; Dang, Guanghui; Liu, Siguo

doi:10.1016/j.micpath.2022.105880

Cited by 7 publications

(5 citation statements)

References 40 publications

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“…UE, including Rv2577 , Rv1983 ( PE_PGRS35 ), and Rv3090 ( Table 1 ). These are described to play a role in M.tb pathogenicity by promoting phagosomal arrest, increased replication, and dissemination (35, 36).…”

Section: Resultsmentioning

confidence: 99%

“…PE_PGRS35 and Rv3090 ) were also upregulated in the E vs. UE comparison. Rv2577 is characterized as an alkaline phosphatase/phosphodiesterase enzyme, which plays a role in M.tb pathogenicity by promoting increased replication and phagosomal arrest in early endosomes (35), and Rv3090 induces late cell apoptosis, resulting in bacterial dissemination and organ damage in mice (36). Overall, these results highlight how exposure to the human elderly lung mucosa prior to infection drives the upregulation of virulence-related genes in M.tb , potentially priming the bacterium to upregulate specific functions involved in mitigating the host immune response and ready its machinery to permeabilize phagosomes before contacting host cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a few other virulence genes that encode phosphatases and proteases were only upregulated in E vs. UE, including Rv2577, Rv1983 (PE_PGRS35), and Rv3090 (Table 1). These are described to play a role in M.tb pathogenicity by promoting phagosomal arrest, increased replication, and dissemination (35,36).…”

Section: E-alf-exposed Mtb Upregulates Genes Associated With Esx-secr...mentioning

confidence: 99%

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Impact of the elderly lung mucosa onMycobacterium tuberculosismetabolic adaptation during infection of alveolar epithelial cells

Olmo-Fontánez,

Allué-Guardia,

Garcia-Vilanova

et al. 2024

Preprint

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Background: Tuberculosis (TB) is one of the top leading causes of death due to a single infectious agent. Upon infection,Mycobacterium tuberculosis(M.tb) is deposited in the alveoli and encounters the lung mucosa or alveolar lining fluid (ALF). We previously determined that increasedM.tbreplication in human macrophages and alveolar epithelial cells (ATs) is mediated by age-associated changes in human ALF. Here we determine the transcriptional profile ofM.tbwhen exposed to healthy ALF from adult (A-ALF) or elderly (E-ALF) individuals before and during infection of ATs.Results: Prior to infection, exposure to E-ALF upregulatesM.tbgenes associated with the ESX-4 secretion system, immunomodulatory proteins from the ESX-5 system, and genes encoding phospholipases, phosphatases, and proteases. During infection, E-ALF exposure upregulates keyM.tbgenes from the ESX-5 secretion system, genes associated with PDIMs biosynthesis and transport, and genes linked to bacterial oxidative stress defense mechanisms.Conclusions: These findings demonstrate how altered ALF in old age can impact the metabolic status ofM.tb, enabling greater adaptation to the host and potentially explainingM.tbincreased survival within host cells. Importantly, we present the first transcriptomic analysis on the impact of the elderly lung mucosa onM.tbpathogenesis during intracellular replication in ATs.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: E-alf-exposed Mtb Upregulates Genes Associated With Esx-secr...mentioning

confidence: 99%

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Impact of the elderly lung mucosa onMycobacterium tuberculosismetabolic adaptation during infection of alveolar epithelial cells

Olmo-Fontánez,

Allué-Guardia,

Garcia-Vilanova

et al. 2024

Preprint

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“…The cell wall–associated protease Rv3090 is reported to be a virulence factor of Mtb. Rv3090 induced the late apoptosis of macrophages, hepatocytes, and lung cells; stimulated the secretion of proinflammatory cytokines; and promoted Mtb survival, thereby contributing to Mtb pathogenicity and dissemination ( 90 ).…”

Section: Detrimental Effects Of Tnf During Mycobacterial Infectionmentioning

confidence: 99%

TNF in Human Tuberculosis: A Double-Edged Sword

Yuk,

Kim,

Kim

et al. 2024

Immune Netw

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TNF, a pleiotropic proinflammatory cytokine, is important for protective immunity and immunopathology during Mycobacterium tuberculosis (Mtb) infection, which causes tuberculosis (TB) in humans. TNF is produced primarily by phagocytes in the lungs during the early stages of Mtb infection and performs diverse physiological and pathological functions by binding to its receptors in a context-dependent manner. TNF is essential for granuloma formation, chronic infection prevention, and macrophage recruitment to and activation at the site of infection. In animal models, TNF, in cooperation with chemokines, contributes to the initiation, maintenance, and clearance of mycobacteria in granulomas. Although anti-TNF therapy is effective against immune diseases such as rheumatoid arthritis, it carries the risk of reactivating TB. Furthermore, TNF-associated inflammation contributes to cachexia in patients with TB. This review focuses on the multifaceted role of TNF in the pathogenesis and prevention of TB and underscores the importance of investigating the functions of TNF and its receptors in the establishment of protective immunity against and in the pathology of TB. Such investigations will facilitate the development of therapeutic strategies that target TNF signaling, which makes beneficial and detrimental contributions to the pathogenesis of TB.

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“…8,9 Most studies have concluded that apoptosis, pyroptosis, and autophagy contribute to the inhibition of pathogen survival, while necrosis and ferroptosis are the main modes of promoting Mtb replication and dissemination. 8 However, apoptosis has been shown in recent studies to promote the survival and release of Mtb, 10 suggesting that the immune outcomes of host cell death modes in a given situation may be multifaceted. Additionally, to address the challenges posed by drug-resistant TB, host-directed therapies (HDTs) targeting host cell death have become an increasing focus of research.…”

mentioning

confidence: 99%

Host‐pathogen dialogues in different cell death modes during Mycobacterium tuberculosis infection

Ruan,

Lyu,

Lai

et al. 2024

Interdisciplinary Medicine

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Tuberculosis (TB) is a fatal infectious disease that continues to pose a serious public health threat. The emergence of drug‐resistant TB has further worsened the burden of the disease. The interaction between the host and the pathogen involves multiple modes of cell death, which play a role in determining immune outcomes. Several studies have established a strong correlation between cell death and TB progression. This review explores the molecular mechanisms of various cell death modes in Mycobacterium tuberculosis (Mtb) infection and how Mtb's virulence effectors regulate these pathways, including apoptosis, autophagy, pyroptosis, ferroptosis, and necrosis. Furthermore, therapeutic strategies targeting cell death pathways have shown promising results in TB treatment. Importantly, this review highlights the significant potential of mitochondria in mediating communication between different cell death modes and influencing the final outcomes. Overall, this work provides a comprehensive summary of the role of cell death in host immune responses and immune evasion by Mtb. It also offers valuable insights into the pathogenesis of TB and immune evasion strategies employed by Mtb and contributes to the development of more effective anti‐TB therapies.

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Mycobacterium tuberculosis protease Rv3090 is associated with late cell apoptosis and participates in organ injuries and mycobacterial dissemination in mice

Cited by 7 publications

References 40 publications

Impact of the elderly lung mucosa onMycobacterium tuberculosismetabolic adaptation during infection of alveolar epithelial cells

Impact of the elderly lung mucosa onMycobacterium tuberculosismetabolic adaptation during infection of alveolar epithelial cells

TNF in Human Tuberculosis: A Double-Edged Sword

Host‐pathogen dialogues in different cell death modes during Mycobacterium tuberculosis infection

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