Bordetella pertussis is a Gram-negative coccobacillus that causes whooping cough or pertussis, a respiratory disease that has recently experienced a resurgence. Upon entering the respiratory tract, B. pertussis colonizes the airway epithelium and attaches to ciliated cells. Here, we used primary human nasal epithelial cells (hNECs) cultured at the air-liquid interface and investigated their interaction with B. pertussis B1917, focusing on the role of the type III secretion system effector protein BteA. In this model, which resembles the epithelial cells of nasal epithelium in vivo, B. pertussis B1917 localized predominantly in the overlying mucus and scarcely colonized the cell cilia. The colonization led to a gradual decline in epithelial barrier function, as shown by measurements of transepithelial electrical resistance (TEER) and staining of the tight junction protein zonula occludens 1. The decrease in TEER occurred independently of the cytotoxic effector protein BteA. Transcriptomic and proteomic analyses of hNECs showed only moderate changes following infection, primarily characterized by increased mucus production, including upregulation of mucin MUC5AC. No profound response to BteA was detected. Furthermore, the infection did not induce production of inflammatory cytokines, suggesting that B. pertussis B1917 evades recognition by hNECs in this model system. These results suggest that the mucus may serve as a niche that allows B. pertussis B1917 to minimize epithelial recognition and damage. The lack of a robust immune response further indicates that additional components of the nasal mucosa, such as innate immune cells, are likely required to initiate an effective host defense.IMPORTANCEThe nasal epithelium is the initial site where Bordetella pertussis comes into contact with the host during respiratory tract infection. In this study, human nasal epithelial cells cultured at the air-liquid interface were established as an in vitro model to investigate the early stages of B. pertussis infection. We showed that the clinical isolate B. pertussis B1917 resides in the mucus during the early stages of colonization without disrupting the epithelial barrier function. Infection results in moderate transcriptomic and proteomic changes, characterized by increased mucus production and minimal inflammatory signaling. These results suggest that B. pertussis B1917 may evade early host recognition by residing in mucus and avoiding direct interaction with epithelial cells. They also highlight the importance of other components of the mucosal immune system, such as resident immune cells, for the initiation of an effective defense.

• Keywords
• Bordetella pertussis, BteA effector, air-liquid interface culture, airway epithelium, human nasal epithelial cell, type III secretion system,
• MeSH
• Bacterial Proteins metabolism   genetics   MeSH
• Bordetella pertussis * pathogenicity   genetics   physiology   MeSH
• Epithelial Cells * microbiology   immunology   metabolism   MeSH
• Virulence Factors, Bordetella metabolism   MeSH
• Mucus microbiology   metabolism   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Mucin 5AC metabolism   genetics   MeSH
• Nasal Mucosa * microbiology   cytology   immunology   MeSH
• Whooping Cough * microbiology   immunology   MeSH
• Proteomics MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bacterial Proteins MeSH
• Virulence Factors, Bordetella MeSH
• Mucin 5AC MeSH

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