"Nature": Shao Feng/Liu Xiaoyun team reveals a new mechanism for pathogenic bacteria to evade innate immunity

▎Editor of WuXi AppTec's content team Since we were young, we have known that we must pay attention to hygiene and avoid "disease in the mouth", because many bacteria in nature may cause diseases once they break through the human immune defense line
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For example, Shigella is a common pathogen, also known as Shigella.
Entering the human body through contaminated food or water may cause bacillary dysentery, causing hemorrhagic diarrhea and severe intestinal inflammation
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Image source: 123RF clarifying how pathogenic bacteria infect host cells and how host cells resist pathogenic bacteria are the basis for providing methods to prevent and treat diseases
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In the field of anti-bacterial natural immunity, Dr.
Shao Feng from the Beijing Institute of Life Sciences has made many important discoveries over the years.
He pointed out that after bacteria invade host cells, the cells cause an antibacterial inflammatory response through a death process called pyroptosis.

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Recently, Dr.
Shao Feng and Dr.
Liu Xiaoyun of Peking University School of Basic Medicine published an important new development in the top academic journal Nature, revealing a new mechanism by which pathogens inhibit host cell pyrolysis.
This discovery Add another milestone to the field of interaction between pathogens and host cells
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In previous studies, Dr.
Shao Feng and others found that after pathogens invaded cells, the caspase (caspase family protease) in the host cell would be activated by lipopolysaccharide (LPS, commonly known as endotoxin), a key component of the bacterial membrane.
Cut the key protein GSDMD, make it perforate in the cell membrane, and finally induce cell pyrolysis
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Related reading: WuXi AppTec Interview with Dr.
Shao Feng-Uncovering the black box of anti-bacterial natural immunity.
However, for their own survival, pathogenic bacteria and host cells have been fighting each other
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The road is one foot high, and the magic is high.
Some pathogenic bacteria have developed the ability to inhibit the function of caspase during the long evolutionary process
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The research team found that, although the caspase-11 in mouse cells played a key role in the process of pathogen-induced pyrolysis, it could not protect mice from Shigella flexneri infection
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Further in vitro cell experiments suggest that Shigella can escape the pyrolysis mediated by the caspase-11-GSDMD pathway in some way
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After screening several effector molecules that Shigella may be used to inhibit the caspase signaling pathway, the researchers identified the effector protein OspC3 secreted by the bacteria, which may be an important weapon with this escape ability, which can inhibit LPS induction.
The cells scorch
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While continuing to explore the mechanism of how OspC3 inhibits caspase function, researchers made unexpected discoveries
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Although OspC3 can be combined with caspase-11, this simple combination is not enough to inhibit it
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A series of biochemical experiments and mass spectrometry analysis showed that when OspC3 is present, the caspase protein undergoes a special "post-translational modification" change
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Specifically, this post-translational modification at first glance is quite similar to the ADP-ribosylation (ADP-ribosylation) discovered decades ago.
NAD+ molecules are used as donors in the process of modifying proteins, but The resulting molecular weight changes are puzzlingly small
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The researchers did not let go of this difference.
After isotopic labeling combined with mass spectrometry and other methods, they finally found that OspC3 mediated a new protein post-translational modification process, which is one step more deamination process than ADP-ribosylation.
, They named it ADP-riboxanation
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▲Researchers have discovered a new type of protein post-translational modification: ADP-riboxanation (picture source: reference [1]) The researchers proved in this paper that when caspase-11 occurs ADP-riboxanation, it can no longer be automated Processing and recognizing and cutting GSDMD, resulting in the innate immunity mediated by cell pyrolysis cannot play its due role
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As a result, the research team solved the mystery of how the pathogenic bacteria Shigella escapes innate immunity
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Of course, the detailed elaboration of the specific mechanism also allows researchers to find a potential strategy to deal with pathogens
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Reference: [1] Zilin Li et al.
, (2021) Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11.
Nature Doi: https://doi.
org/10.
1038/s41586-021-04020-1[2 ] Feng Shao/Xiaoyun Liu’s team reveals a new mechanism by which pathogens inhibit the pyrolysis of host cells-a new protein post-translational modification Retrieved Nov.
2, 2021 from http:// =15&id=2440