Co-infection of respiratory tract viruses and bacteria often result in excess mortality, especially pneumonia caused by influenza
viruses and Streptococcus pneumoniae. However, the synergistic mechanisms remain poorly understood. Therefore, it
is necessary to develop a clearer understanding of the molecular basis of the interaction between influenza virus and Streptococcus
pneumonia. Here, we developed the BALB/c mouse model and the A549 cell model to investigate inflammation
and pyroptotic cell death during co-infection. Co-infection significantly activated the NLRP3 inflammasome and induced
pyroptotic cell death, correlated with excess mortality. The E3 ubiquitin ligase NEDD4 interacted with both NLRP3 and
GSDMD, the executor of pyroptosis. NEDD4 negatively regulated NLRP3 while positively regulating GSDMD, thereby
modulating inflammation and pyroptotic cell death. Our findings suggest that NEDD4 may play a crucial role in regulating
the GSDMD-mediated pyroptosis signaling pathway. Targeting NEDD4 represents a promising approach to mitigate excess
mortality during influenza pandemics by suppressing synergistic inflammation during co-infection of influenza A virus and
Streptococcus pneumoniae.
Overexpression of DTX1 inhibits D-GalN/TNF-α-induced pyroptosis and inflammation in hepatocytes by regulating NLRP3 ubiquitination Mingshui Liu, Jing Gu, Li Chen, Wei Sun, Xiaoping Huang, Jianhe Gan Toxicology Research.2024;[Epub] CrossRef
NLRP3 Inflammasomes: Dual Function in Infectious Diseases Yanbo Li, Rui Qiang, Zhengmin Cao, Qingjuan Wu, Jiuchong Wang, Wenliang Lyu The Journal of Immunology.2024; 213(4): 407. CrossRef
β-Lactam antibiotics are the most commonly prescribed antibiotics
worldwide; however, antimicrobial resistance (AMR)
is a global challenge. The β-lactam resistance in Gram-negative
bacteria is due to the production of β-lactamases, including
extended-spectrum β-lactamases, metallo-β-lactamases,
and carbapenem-hydrolyzing class D β-lactamases.
To restore the efficacy of BLAs, the most successful strategy
is to use them in combination with β-lactamase inhibitors
(BLI). Here we review the medically relevant β-lactamase
families and penicillins, diazabicyclooctanes, boronic acids,
and novel chemical scaffold-based BLIs, in particular approved
and under clinical development.
Citations
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