The research of Professor Qian Feng's team of Shanghai Jiaotong University revealed a new mechanism of pneumonia caused by methicillus-resistant Staphylococcus aureus

On January 2, 2023, Professor Qian Feng's research group of the School of Pharmacy of Shanghai Jiao Tong University published a report entitled Staphylococcal virulence factor HlgB targets the endoplasmic-reticulum-resident E3 ubiquitin ligase AMFR to the top international academic journal Nature Microbiology (IF=30.
964).
Research paper
to promote pneumonia.
The study found that Methicillin-resistant Staphylococcus aureus (MRSA) interacts with the endoplasmic reticulum-associated E3 ubiquitin ligase AMFR through its virulence factor HlgB, promotes the production of inflammatory cytokines by macrophages, and mediates the inflammatory response
induced by intracellular bacteria MRSA.

Methicillin-resistant Staphylococcus aureus (MRSA) is the main pathogen of nosocomial and community infections, with strong pathogenicity and broad-spectrum drug resistance, resulting in high mortality rate of clinical infection and difficult
treatment.
Therefore, it is of great scientific significance
to elucidate the pathogenic mechanism of MRSA and the molecular mechanism of inducing inflammatory response.

In the body's immune defense, MRSA can escape the degradation of cellular lysosomes after being phagocytosed by macrophages, and survive in host cells, inducing severe inflammatory responses
by interacting with intracellular signaling molecules.
But this regulatory mechanism is unclear
.

In this study, the research team first found that intracellular surviving MRSA is mainly enriched in the endoplasmic reticulum
.
Through endoplasmic reticulum-associated CRISPR-Cas9 gRNA library screening, the researchers found that endoplasmic reticulum-associated E3 ubiquitin ligase AMFR was involved in intracellular MRSA-induced inflammatory response, and myeloid cell-specific AMFR knockout mice had significantly reduced
the inflammatory response induced by MRSA infection.

Molecular mechanism studies have found that MRSA induces AMFR to interact with intracellular signaling molecule TAB3 through its virulence factor HlgB, and causes ubiquitination modification of K27 position of TAB3 through lysine at position 649 on TAB3, activating the downstream signaling molecules TAK1 and NF-kB signaling pathway
.

This study elucidates the molecular mechanism of MRSA as an inducing inflammatory response in intracellular bacteria, reveals the new mechanism of MRSA inducing AMFR to interact with TAB3 through the virulence factor HlgB, regulating the NF-kB signaling pathway, and then regulating the inflammatory response induced by MRSA, and making HlgB and AMFR a novel drug target for the treatment of MRSA infectious pneumonia
.

Associate Professor Sun Lei of the School of Pharmacy, Shanghai Jiao Tong University is the first author of the paper, and Professor Qian Feng and Associate Professor Sun Lei of the School of Pharmacy of Shanghai Jiao Tong University are the co-corresponding authors
of the paper.
Professor Qian Feng's research group mainly studies the regulatory mechanism
of respiratory diseases including infectious pneumonia, adult respiratory distress syndrome, asthma and pulmonary fibrosis.
This research work was supported
by the National Natural Science Foundation of China and the Shanghai Municipal Natural Science Foundation.

Link to the paper: