scholarly journals The Bordetella pertussis Type III Secretion System Tip Complex Protein Bsp22 Is Not a Protective Antigen and Fails To Elicit Serum Antibody Responses during Infection of Humans and Mice

2014 ◽  
Vol 82 (7) ◽  
pp. 3088-3088
Author(s):  
Rodrigo Villarino Romero ◽  
Ilona Bibova ◽  
Ondrej Cerny ◽  
Branislav Vecerek ◽  
Tomas Wald ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Type Iii Secretion ◽  
Protective Antigen ◽  
Serum Antibody ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Antibody Responses ◽  
Type Iii ◽  
Complex Protein

scholarly journals The Bordetella pertussis Type III Secretion System Tip Complex Protein Bsp22 Is Not a Protective Antigen and Fails To Elicit Serum Antibody Responses during Infection of Humans and Mice

2013 ◽  
Vol 81 (8) ◽  
pp. 2761-2767 ◽  
Author(s):  
Rodrigo Villarino Romero ◽  
Ilona Bibova ◽  
Ondrej Cerny ◽  
Branislav Vecerek ◽  
Tomas Wald ◽  
...  
Keyword(s):  
Antibody Response ◽  
Bordetella Pertussis ◽  
Type Iii Secretion ◽  
Protective Antigen ◽  
Serum Antibody ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Content Type ◽  
Serum Antibody Response ◽  
Complex Protein

ABSTRACTThe type III secretion system (T3SS) of pathogenic bordetellae employs a self-associating tip complex protein Bsp22. This protein is immunogenic during infections byBordetella bronchisepticaand could be used as a protective antigen to immunize mice againstB. bronchisepticachallenge. Since low-passage clinical isolates of the human pathogenBordetella pertussisproduce a highly homologous Bsp22 protein (97% homology), we examined its vaccine and diagnostic potential. No Bsp22-specific antibodies were, however, detected in serum samples from 36 patients with clinically and serologically confirmed whooping cough disease (pertussis syndrome). Moreover, although the induction of Bsp22 secretion by the laboratory-adapted 18323 strain in the course of mice lung infection was observed, theB. pertussis18323-infected mice did not mount any detectable serum antibody response against Bsp22. Furthermore, immunization with recombinant Bsp22 protein yielded induction of high Bsp22-specific serum antibody titers but did not protect mice against an intranasal challenge withB. pertussis18323. Unlike forB. bronchiseptica, hence, the Bsp22 protein is nonimmunogenic, and/or the serum antibody response to it is suppressed, duringB. pertussisinfections of humans and mice.

scholarly journals N-Terminus of IpaB Provides a Potential Anchor to the Shigella Type III Secretion System Tip Complex Protein IpaD

Biochemistry ◽  
2013 ◽  
Vol 52 (49) ◽  
pp. 8790-8799 ◽  
Author(s):  
Nicholas E. Dickenson ◽  
Olivia Arizmendi ◽  
Mrinalini K. Patil ◽  
Ronald T. Toth ◽  
C. Russell Middaugh ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
N Terminus ◽  
Complex Protein

scholarly journals Transcriptional Downregulation of a Type III Secretion System under Reducing Conditions in Bordetella pertussis

2020 ◽  
Vol 202 (21) ◽  
Author(s):  
Masataka Goto ◽  
Tomoko Hanawa ◽  
Akio Abe ◽  
Asaomi Kuwae
Keyword(s):  
Bordetella Pertussis ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Culture Conditions ◽  
Secretion System ◽  
Host Cells ◽  
Secreted Proteins ◽  
Content Type ◽  
Type Iii ◽  
Reducing Conditions

ABSTRACT Bordetella pertussis uses a type III secretion system (T3SS) to inject virulence proteins into host cells. Although the B. pertussis T3SS was presumed to be involved in host colonization, efficient secretion of type III secreted proteins from B. pertussis has not been observed. To investigate the roles of type III secreted proteins during infection, we attempted to optimize culture conditions for the production and secretion of a type III secreted protein, BteA, in B. pertussis. We observed that B. pertussis efficiently secretes BteA in ascorbic acid-depleted (AsA−) medium. When L2 cells, a rat lung epithelial cell line, were infected with B. pertussis cultured in the AsA− medium, BteA-dependent cytotoxicity was observed. We also performed an immunofluorescence assay of L2 cells infected with B. pertussis. Clear fluorescence signals of Bsp22, a needle structure of T3SS, were detected on the bacterial surface of B. pertussis cultured in the AsA− medium. Since ascorbic acid is known as a reducing agent, we cultured B. pertussis in liquid medium containing other reducing agents such as 2-mercaptoethanol and dithioerythritol. Under these reducing conditions, the production of type III secreted proteins was repressed. These results suggest that in B. pertussis, the production and secretion of type III secreted proteins are downregulated under reducing conditions. IMPORTANCE The type III secretion system (T3SS) of Bordetella pertussis forms a needlelike structure that protrudes from the bacterial cell surface. B. pertussis uses a T3SS to translocate virulence proteins called effectors into host cells. The culture conditions for effector production in B. pertussis have not been investigated. We attempted to optimize culture medium compositions for producing and secreting type III secreted proteins. We found that B. pertussis secretes type III secreted proteins in reducing agent-deprived liquid medium and that BteA-secreting B. pertussis provokes cytotoxicity against cultured mammalian cells. These results suggest that redox signaling is involved in the regulation of B. pertussis T3SS.

scholarly journals Bordetella pertussis Expresses a Functional Type III Secretion System That Subverts Protective Innate and Adaptive Immune Responses

2008 ◽  
Vol 76 (3) ◽  
pp. 1257-1266 ◽  
Author(s):  
Neil K. Fennelly ◽  
Federico Sisti ◽  
Sarah C. Higgins ◽  
Pádraig J. Ross ◽  
Han van der Heide ◽  
...  
Keyword(s):  
Immune Responses ◽  
Bordetella Pertussis ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Effector Proteins ◽  
Host Cells ◽  
Adaptive Immune Responses ◽  
Type Iii ◽  
Adaptive Immune

ABSTRACT Certain bacteria use a type III secretion system (TTSS) to deliver effector proteins that interfere with cell function into host cells. While transcription of genes encoding TTSS components has been demonstrated, studies to date have failed to identify TTSS effector proteins in Bordetella pertussis. Here we present the first evidence of a functionally active TTSS in B. pertussis. Three known TTSS effectors, Bsp22, BopN, and BopD, were identified as TTSS substrates in B. pertussis 12743. We found expression of Bsp22 in a significant proportion of clinical isolates but not in common laboratory-adapted strains of B. pertussis. We generated a TTSS mutant of B. pertussis 12743 and showed that it induced significantly lower respiratory tract colonization in mice than the wild-type bacteria. Respiratory infection of mice with the mutant bacteria induced significantly greater innate proinflammatory cytokine production in the lungs soon after challenge, and this correlated with significantly higher antigen-specific interleukin-17, gamma interferon, and immunoglobulin G responses later in infection. Our findings suggest that the TTSS subverts innate and adaptive immune responses during infection of the lungs and may be a functionally important virulence factor for B. pertussis infection of humans.

scholarly journals Transcriptional Downregulation of a Type III Secretion System under Reducing Conditions in Bordetella pertussis

2020 ◽  
Author(s):  
Masataka Goto ◽  
Tomoko Hanawa ◽  
Akio Abe ◽  
Asaomi Kuwae
Keyword(s):  
Bordetella Pertussis ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Culture Conditions ◽  
Secretion System ◽  
Host Cells ◽  
Secreted Proteins ◽  
Virulence Proteins ◽  
Type Iii ◽  
Reducing Conditions

ABSTRACTBordetella pertussis uses a type III secretion system (T3SS) to inject virulence proteins into host cells. Although the B. pertussis T3SS was presumed to be involved in host colonization, the efficient secretion of type III secreted proteins from B. pertussis has not been observed. To investigate the roles of type III secreted proteins during infection, we attempted to optimize culture conditions for the production and secretion of a type III secreted protein, BteA, in B. pertussis. We observed that B. pertussis efficiently secretes BteA in ascorbic acid-depleted (AsA−) medium. When L2 cells, a rat lung epithelial cell line, were infected with B. pertussis cultured in the AsA− medium, BteA-dependent cytotoxicity was observed. We also performed an immunofluorescence assay of L2 cells infected with B. pertussis. The clear fluorescence signals of Bsp22, a needle structure of T3SS, were detected on the bacterial surface of B. pertussis cultured in the AsA− medium. Since ascorbic acid is known as a reducing agent, we cultured B. pertussis in liquid medium containing other reducing agents such as 2-mercaptoethanol and dithioerythritol. Under these reducing conditions, the production of type III secreted proteins was repressed. These results suggest that in B. pertussis, the production and secretion of type III secreted proteins are downregulated under reducing conditions.IMPORTANCEThe type III secretion system (T3SS) of Bordetella pertussis forms a needle-like structure that protrudes from the bacterial cell surface. B. pertussis uses T3SS to translocate virulence proteins called effectors into host cells. The culture conditions for effector production in B. pertussis have not been investigated. We attempted to optimize culture medium compositions for producing and secreting type III secreted proteins. We found that B. pertussis secretes type III secreted proteins in reducing agent-deprived liquid medium, and that BteA-secreting B. pertussis provokes cytotoxicity against cultured mammalian cells. These results suggest that redox signaling is involved in the regulation of B. pertussis T3SS.

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

2020 ◽  
Author(s):  
Jan Bayram ◽  
Ivana Malcova ◽  
Larisa Sinkovec ◽  
Jana Holubova ◽  
Gaia Streparola ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Bordetella Pertussis ◽  
Hela Cells ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Human Infant ◽  
Effector Protein ◽  
Alanine Residue ◽  
Type Iii

AbstractBordetella 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 presence of an alanine residue inserted at position 503 (A503) of Bp BteA accounts for its strongly attenuated cytotoxic potency. 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, 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 summaryPertussis 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.

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