Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue

Autor: Peter Sebo, Jana Kamanova, Jan Kučera, Ivana Malcova, Jana Holubova, Radislav Sedlacek, David Jurnecka, Gaia Streparola, Larisa Sinkovec, Jan Bayram
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Bacterial Diseases
Bordetella pertussis
Pulmonology
Bordetella
Whooping Cough
Cytotoxicity
Yeast and Fungal Models
Secretion Systems
Pathology and Laboratory Medicine
Toxicology
Biochemistry
Mice
Medical Conditions
Microbial Physiology
Medicine and Health Sciences
Type III Secretion Systems
Cytotoxic T cell
Bacterial Physiology
Amino Acids
Biology (General)
Pathogen
Mice
Inbred BALB C
0303 health sciences
Alanine
Bordetella bronchiseptica
Virulence
biology
Organic Compounds
Effector
Chemistry
Eukaryota
Bacterial Pathogens
Infectious Diseases
Experimental Organism Systems
Medical Microbiology
Physical Sciences
Saccharomyces Cerevisiae
Female
Pathogens
Research Article
Virulence Factors
QH301-705.5
Immunology
Research and Analysis Methods
Microbiology
Saccharomyces
Respiratory Disorders
03 medical and health sciences
Model Organisms
Immune system
Pertussis
Bacterial Proteins
Virology
Genetics
Animals
Humans
Secretion
Microbial Pathogens
Molecular Biology
030304 developmental biology
Bacteria
030306 microbiology
Organic Chemistry
Organisms
Fungi
Chemical Compounds
Biology and Life Sciences
Proteins
Bacteriology
Gene Expression Regulation
Bacterial
RC581-607
biology.organism_classification
Yeast
Aliphatic Amino Acids
Respiratory Infections
Mutation
Animal Studies
Parasitology
Immunologic diseases. Allergy
HeLa Cells
Zdroj: PLoS Pathogens, Vol 16, Iss 8, p e1008512 (2020)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Bordetella bronchiseptica and Bordetella pertussis are closely related respiratory pathogens that evolved from a common bacterial ancestor. While B. bronchiseptica has an environmental reservoir and mostly establishes chronic infections in a broad range of mammals, B. pertussis is a human-specific pathogen causing acute pulmonary pertussis in infants and whooping cough illness in older humans. Both species employ a type III secretion system (T3SS) to inject a cytotoxic BteA effector protein into host cells. However, compared to the high BteA-mediated cytotoxicity of B. bronchiseptica, the cytotoxicity induced by B. pertussis BteA (Bp BteA) appears to be quite low and this has been attributed to the reduced T3SS gene expression in B. pertussis. We show that the presence of an alanine residue inserted at position 503 (A503) of Bp BteA accounts for its strongly attenuated cytotoxic potency. The deletion of A503 from Bp BteA greatly enhanced the cytotoxic activity of B. pertussis B1917 on mammalian HeLa cells and expression of Bp BteAΔA503 was highly toxic to Saccharomyces cerevisiae cells. Vice versa, insertion of A503 into B. bronchiseptica BteA (Bb BteA) strongly decreased its cytotoxicity to yeast and HeLa cells. Moreover, the production of Bp BteAΔA503 increased virulence of B. pertussis B1917 in the mouse model of intranasal infection (reduced LD50) but yielded less inflammatory pathology in infected mouse lungs at sublethal infectious doses. This suggests that A503 insertion in the T3SS effector Bp BteA may represent an evolutionary adaptation that fine-tunes B. pertussis virulence and host immune response.
Author summary Pertussis remains the least-controlled vaccine-preventable infectious disease and the mechanisms by which Bordetella pertussis subverts defense mechanisms of human airway mucosa remain poorly understood. We found that B. pertussis had the cytotoxic activity of its type III secretion system-delivered effector BteA strongly attenuated by insertion of an alanine residue at position 503 as compared to the BteA homologue of the animal pathogen B. bronchiseptica. This functional adaptation reduced the capacity of B. pertussis to suppress host inflammatory response and may contribute to an acute course of the pulmonary form of human infant pertussis.
Databáze: OpenAIRE
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