Bacterial Toxin and Effector Regulation of Intestinal Immune Signaling

Woida, Patrick J.; Satchell, K.J.F.

doi:10.3389/fcell.2022.837691

Cited by 3 publications

(3 citation statements)

References 110 publications

(162 reference statements)

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“…Recent evidence has revealed that pathogens maneuver the host immune response to facilitate their own survival by bacterial effectors 23 , 24 . Nucleic acid or heat-killed B. pseudomallei was used to treat RAW264.7 cells.…”

Section: Resultsmentioning

confidence: 99%

Burkholderia pseudomallei BipD modulates host mitophagy to evade killing

Nan,

Rao,

Tang

et al. 2024

Nat Commun

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Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.

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Section: Resultsmentioning

confidence: 99%

Burkholderia pseudomallei BipD modulates host mitophagy to evade killing

Nan,

Rao,

Tang

et al. 2024

Nat Commun

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“…However, the bacteria, which co-evolved with such responses, 'fight back' by activating secretion systems, releasing toxins and effector proteins that eliminate, or diminish the ability of host cells to activate the MAPKs (see Figure 2, Table 1 and Refs. [10,11,29,166]). It is possible that the extent of this effect determines whether an acute infectious diarrheal disease will emerge, or not.…”

Section: Discussionmentioning

confidence: 99%

Mitogen-Activated Protein Kinases (MAPKs) and Enteric Bacterial Pathogens: A Complex Interplay

Nandi

Aroeti

2023

IJMS

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Diverse extracellular and intracellular cues activate mammalian mitogen-activated protein kinases (MAPKs). Canonically, the activation starts at cell surface receptors and continues via intracellular MAPK components, acting in the host cell nucleus as activators of transcriptional programs to regulate various cellular activities, including proinflammatory responses against bacterial pathogens. For instance, binding host pattern recognition receptors (PRRs) on the surface of intestinal epithelial cells to bacterial pathogen external components trigger the MAPK/NF-κB signaling cascade, eliciting cytokine production. This results in an innate immune response that can eliminate the bacterial pathogen. However, enteric bacterial pathogens evolved sophisticated mechanisms that interfere with such a response by delivering virulent proteins, termed effectors, and toxins into the host cells. These proteins act in numerous ways to inactivate or activate critical components of the MAPK signaling cascades and innate immunity. The consequence of such activities could lead to successful bacterial colonization, dissemination, and pathogenicity. This article will review enteric bacterial pathogens’ strategies to modulate MAPKs and host responses. It will also discuss findings attempting to develop anti-microbial treatments by targeting MAPKs.

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“…Recent evidence has revealed that pathogens maneuver the host immune response to facilitate their own survival by bacterial effectors 22,23 . Nucleic acid or heat-killed B. pseudomallei was used to treat RAW264.7 cells.…”

Section: Bipd Induced Host Mitophagy Post B Pseudomallei Infectionmentioning

confidence: 99%

Burkholderia pseudomallei BipD hijacks host KLHL9/KLHL13/CUL3 E3 ligase to ubiquitinate IMMT that initiates mitophagy to evade killing

Li,

Nan,

Rao

et al. 2023

Preprint

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Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type Ⅲ secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a new substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Together, our findings reveal a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.

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Bacterial Toxin and Effector Regulation of Intestinal Immune Signaling

Cited by 3 publications

References 110 publications

Burkholderia pseudomallei BipD modulates host mitophagy to evade killing

Burkholderia pseudomallei BipD modulates host mitophagy to evade killing

Mitogen-Activated Protein Kinases (MAPKs) and Enteric Bacterial Pathogens: A Complex Interplay

Burkholderia pseudomallei BipD hijacks host KLHL9/KLHL13/CUL3 E3 ligase to ubiquitinate IMMT that initiates mitophagy to evade killing

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