Aminopeptidase MNP-1 triggers intestine protease production by activating daf-16 nuclear location to degrade pore-forming toxins in Caenorhabditis elegans
Por:
Chen, Feng, Pang, Cuiyun, Zheng, Ziqiang, Zhou, Wei, Guo, Zhiqing, Xiao, Danyang, Du, Hongwen, Bravo, Alejandra, Soberon, Mario R., Sun, Ming R., Peng, Donghai R.
Publicada:
1 jul 2023
Resumen:
Pore-forming toxins (PFTs) are effective tools for pathogens infection.
By disrupting epithelial barriers and killing immune cells, PFTs
promotes the colonization and reproduction of pathogenic microorganisms
in their host. In turn, the host triggers defense responses, such as
endocytosis, exocytosis, or autophagy. Bacillus thuringiensis (Bt)
bacteria produce PFT, known as crystal proteins (Cry) which damage the
intestinal cells of insects or nematodes, eventually killing them. In
insects, aminopeptidase N (APN) has been shown to act as an important
receptor for Cry toxins. Here, using the nematode Caenorhabditis elegans
as model, an extensive screening of APN gene family was performed to
analyze the potential role of these proteins in the mode of action of
Cry5Ba against the nematode. We found that one APN, MNP-1, participate
in the toxin defense response, since the mnp-1(ok2434) mutant showed a
Cry5Ba hypersensitive phenotype. Gene expression analysis in
mnp-1(ok2434) mutant revealed the involvement of two protease genes,
F19C6.4 and R03G8.6, that participate in Cry5Ba degradation. Finally,
analysis of the transduction pathway involved in F19C6.4 and R03G8.6
expression revealed that upon Cry5Ba exposure, the worms up regulated
both protease genes through the activation of the FOXO transcription
factor DAF-16, which was translocated into the nucleus. The nuclear
location of DAF-16 was found to be dependent on mnp-1 under Cry5Ba
treatment. Our work provides evidence of new host responses against PFTs
produced by an enteric pathogenic bacterium, resulting in activation of
host intestinal proteases that degrade the PFT in the intestine.
Author summaryPore-forming toxins (PFTs) have a crucial role in the
pathogenesis of microbial pathogens. Meanwhile, hosts mediate different
strategies to resist PFTs at the cellular level, such as endocytosis,
exocytosis, autophagy, and MAPK or inflammasome signaling pathways. Here
we show that the nematode Caenorhabditis elegans respond to PFTs
inducing their proteolysis by up regulating intestinal proteases through
the induction of FOXO transcription factor DAF-16 that showed nuclear
location. Our results indicate that animals not only trigger defense
mechanisms after PFTs intoxication at the cellular level, but also could
eliminate PFTs in the intestine lumen, an effective additional strategy
for animals to resist PFTs, especially those produced by enteric
bacterial pathogens. Since, the FOXO transcription factor DAF-16 is
conserved from nematodes to mammals, it is possible that the degradation
of PFT by modulating intestinal proteases may be a common defense
strategy against bacterial infections.
Filiaciones:
Chen, Feng:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
Pang, Cuiyun:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
Zheng, Ziqiang:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
Zhou, Wei:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
Guo, Zhiqing:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
Xiao, Danyang:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
Du, Hongwen:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
Bravo, Alejandra:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca, Morelos, Mexico
Soberon, Mario R.:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca, Morelos, Mexico
Sun, Ming R.:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
Peng, Donghai R.:
Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
gold, Gold
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