Most cited article - PubMed ID 39570047
The Bordetella effector protein BteA induces host cell death by disruption of calcium homeostasis
Pertussis, or whooping cough, is a highly contagious and acute respiratory illness caused primarily by the gram-negative coccobacillus Bordetella pertussis. Despite near-universal vaccination, pertussis remains one of the least-controlled vaccine-preventable infectious diseases. Since 2023, pertussis incidence has been rising, and widespread pertussis outbreaks have resurged in many countries. In response to these emerging challenges, almost 300 experts from institutions across 24 countries convened at the 14th International Bordetella Symposium in Prague, Czech Republic, from 24 to 28 June 2024 to discuss pertussis epidemiology and research and strategies to mitigate the global pertussis burden. We present here the highlights of the symposium, comprising epidemiological and clinical aspects of Bordetella infections, results of clinical trials of pertussis vaccination in pregnant women and effectiveness of maternal vaccination in protecting newborn infants in Africa and Europe, the controlled human infection model (CHIM), and the latest insights into the biology, immunology, and pathogenesis of B. pertussis infection.
- Keywords
- Bordetella pertussis, epidemiology, pathogenesis, toxins, vaccines, virulence,
- MeSH
- Bordetella pertussis * immunology MeSH
- Global Health MeSH
- Congresses as Topic MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Whooping Cough * prevention & control epidemiology microbiology MeSH
- Pertussis Vaccine administration & dosage immunology MeSH
- Pregnancy MeSH
- Vaccination MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Congress MeSH
- Review MeSH
- Names of Substances
- Pertussis Vaccine MeSH
The type III secretion system (T3SS) is an important virulence factor of Gram-negative bacteria, including the genus Aeromonas, which represents a diverse group of aquatic bacteria. One member of the genus, Aeromonas schubertii, is an emerging pathogen in aquaculture, causing high mortality in snakehead fish. Infections are associated with the formation of white nodules in the internal organs, likely resulting from A. schubertii-induced apoptosis and/or necrosis. The present study investigates the type strain A. schubertii ATCC 43700, which encodes two distinct T3SSs located within Aeromonas pathogenicity islands 1 and 2, referred here to as API1 and API2. We analyzed their role in A. schubertii-induced cytotoxicity and identified novel T3SS effector proteins. Infections of HeLa cells revealed that API1, but not API2, mediates cytotoxicity and induces both apoptotic and necrotic cell death. Moreover, proteomic analysis identified seven candidate effectors secreted by the API1 injectisome. These included two previously described effectors, AopH and AopO from A. salmonicida, as well as five novel effectors named AopI, AopJ, AopL, AopT, and AopU, whose injection into host cells was validated using a split luciferase reporter system. Functional characterization showed that AopL, a homolog of Vibrio parahaemolyticus VopQ, induces caspase-3/-7-independent necrosis, while AopI, a homolog of ExoY from Pseudomonas aeruginosa, suppresses caspase-3/-7 activation and necrosis, revealing a pro-survival function. These results demonstrate the critical role of the API1 injectisome in A. schubertii-induced cytotoxicity and provide experimental identification of novel Aeromonas effectors that cooperate to fine-tune host cell cytotoxicity.
- Keywords
- Aeromonas, Aeromonas schubertii, ExoY, VopQ, cytotoxicity, type III secretion system effectors,
- MeSH
- Aeromonas * genetics pathogenicity physiology MeSH
- Apoptosis MeSH
- Bacterial Proteins * metabolism genetics MeSH
- Virulence Factors * metabolism genetics MeSH
- Gram-Negative Bacterial Infections * microbiology veterinary MeSH
- HeLa Cells MeSH
- Humans MeSH
- Fish Diseases * microbiology MeSH
- Type III Secretion Systems * metabolism genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Bacterial Proteins * MeSH
- Virulence Factors * MeSH
- Type III Secretion Systems * MeSH