Bordetella pertussis isolates vary in their interactions with human complement components

Abstract

Whooping cough is a re-emerging respiratory tract infection. It has become clear that there is a need for better understanding of protective immune responses and variation between Bordetella pertussis strains to aid the development of improved vaccines. In order to survive in the host, B. pertussis has evolved mechanisms to evade complement-mediated killing, including the ability to bind complement-regulatory proteins. Here we evaluate the variation in interactions with the complement system among recently isolated strains. Isolates whose genomes appear highly similar and cluster together on a SNP-based dendrogram were found to vary significantly in resistance to complement-mediated killing and in the deposition of C3b/iC3b, C5b-9 and C1 esterase inhibitor (C1-INH). The key role of Vag8 as a receptor for C1-INH was confirmed and its expression was shown to vary in a panel of isolates. A Vag8 knockout mutant showed increased sensitivity to complement-mediated killing. Antibodies in convalescent sera blocked C1-INH binding to B. pertussis and may play an important role in natural immunity.

Development and Standardization of a High-Throughput Bordetella pertussis Growth-Inhibition Assay

“…B. pertussis has developed several complement evasion strategies to subvert host innate immunity (Thiriard et al, 2018), and complement sensitivity may vary among different clinical isolates (Stefanelli et al, 2006;Brookes et al, 2018) and depends on the secretion of various virulence factors that can be modulated during growth (Barnes and Weiss, 2002) and culture conditions (Luu et al, 2017). In this study, we show that the BGIA can be used to measure complement sensitivity and confirm that sensitivity differs between strains, bacterial growth medium and complement source.…”

“…To evaluate the role of complement in B. pertussis growth inhibition, we performed the BGIA on IgG-and IgM-depleted human serum (HS), on a commercial guinea pig serum (GPS) and on a baby rabbit complement (BRC). However, sensitivity of B. pertussis to complement may vary from strain to strain (Brookes et al, 2018) and according to the growth conditions (Luu et al, 2017). We therefore compared the laboratory strain BPSM to the more recent clinical isolate B1917 each grown in liquid SS or THIJS medium.…”

Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor

“…We suggest that B. pertussis uses this complement evasion strategy to aid in the prevention of opsonization and complement-mediated lysis. Vag8 is not only secreted but also present on the bacterial surface where it binds to C1-INH ( 19 , 43 ). Binding of C1-INH to the bacterial surface could also result in the inhibition of complement activation which has been shown for other bacteria such as Borrelia recurrentis ( 44 ).…”

Detection of opsonizing antibodies directed against a recently circulating Bordetella pertussis strain in paired plasma samples from symptomatic and recovered pertussis patients

“…Additionally, protective mechanisms including neutrophil respiratory burst 45 and subsequent killing, as well as complement-mediated killing of B . pertussis 46 – 48 could be studied. Recently, levels of specific memory B cells, that can give rise to a fast increase in antibody levels upon an infection with B .…”