A Proteomic Characterization of Bordetella pertussis Clinical Isolates Associated with a California State Pertussis Outbreak

Abstract

Bordetella pertussis (Bp) is the etiologic agent of pertussis (whooping cough), a highly communicable infection. Although pertussis is vaccine preventable, in recent years there has been increased incidence, despite high vaccine coverage. Possible reasons for the rise in cases include the following: Bp strain adaptation, waning vaccine immunity, increased surveillance, and improved clinical diagnostics. A pertussis outbreak impacted California (USA) in 2010; children and preadolescents were the most affected but the burden of disease fell mainly on infants. To identify protein biomarkers associated with this pertussis outbreak, we report a whole cellular protein characterization of six Bp isolates plus the pertussis acellular vaccine strain Bp Tohama I (T), utilizing gel-free proteomics-based mass spectrometry (MS). MS/MS tryptic peptide detection and protein database searching combined with western blot analysis revealed three Bp isolates in this study had markedly reduced detection of pertactin (Prn), a subunit of pertussis acellular vaccines. Additionally, antibody affinity capture technologies were implemented using anti-Bp T rabbit polyclonal antisera and whole cellular proteins to identify putative immunogens. Proteome profiling could shed light on pathogenesis and potentially lay the foundation for reduced infection transmission strategies and improved clinical diagnostics.

Proteomic Adaptation of Australian Epidemic Bordetella pertussis

“…However, there are several limitations with 2D gels including that it cannot analyze the whole proteome and that less abundant yet equally important proteins may be missed . Williamson et al employed shotgun proteomics to also compare the differences in expression of vaccine antigens in the whole cell and supernatant. This study found differences in the expression of ACV antigens between current clinical strains from California and Tohama I.…”

“…In the whole cell, 202 proteins (24%) detected have been previously found to be immunogenic while in the secretome there were 91 immunogenic proteins (43%) . The difference was significant using a Fisher's exact test ( p < 0.0001).…”

“…In the secretome, FhaB and Prn were borderline different; however, for FhaB, MRM‐hr confirmed no difference whilst Prn could not be confirmed as no suitable peptides were found for MRM‐hr. A previous proteomic study compared the expression between Californian ptxP3 strains and Tohama I . They found differences in expression of ACV antigens between ptxP3 strains and Tohama I.…”

Signal transduction-dependent small regulatory RNA is involved in glutamate metabolism of the human pathogen Bordetella pertussis

“…Recently, increased abundance of the BP3831 protein in the secretome of the Australian epidemic strain was documented and suggested to be linked with increased fitness of this strain (Luu et al 2018). Furthermore, BP3831 protein was identified within the surface proteome of B. pertussis and was also found to be immunogenic (Tefon et al 2011;Williamson et al 2015). B. pertussis as a strictly human pathogen faces upon infection several stresses resulting from nutrient scarcity as well as from the immune response of the host.…”

Characterization of a predominant Bordetella pertussis strain isolated from Iranian patients

“…The genomic pattern of this unique clone was similar to that of the most common profile of BpSR11 clone in European countries [22]. Since B. pertussis evolves by time, recent studies have suggested that the use of circulating strains in improved wP or aP vaccines might be an appropriate mean to decrease and eventually eradicate B. pertussis from the globe [23,24,13]. It is also envisaged that data gathered from monitoring and characterization of B. pertussis circulating isolates would lead to a new generation of wP vaccines with better efficacy than today's vaccines.…”