Background: Bordetella pertussis is the causative agent of whooping cough, the least controlled vaccine-preventable disease in Australia. Since the switch to the acellular vaccine, the predominant strains in Australia changed to single nucleotide polymorphism (SNP) Cluster I (carrying pertussis toxin promoter ptxP3 and pertactin prn2 alleles) from SNP Cluster II (non-ptxP3/non-prn2)(1). The former was responsible for the 2008 – 2012 Australian epidemic. We have shown that SNP Cluster I has higher fitness in an in vivo mouse competition assay than SNP Cluster II, regardless of the host’s immunisation status(2). The aim of this study was to identify key proteomic differences that may explain higher fitness levels of B. pertussis SNP Cluster I strains.
Methods: B. pertussis strains L1423 (SNP Cluster I) and L1191 (SNP Cluster II) were grown in THIJS media(3). Isobaric tags for relative and absolute quantification (ITRAQ) and multiple reaction monitoring (MRM) were used to quantify proteins in the whole cell and secretome. T-test with false discovery rate correction was used to determine significance (q < 0.05).
Results: The majority of the whole cell proteome and secretome were identical between the two strains except for a few key expression differences. In the whole cell, 9 proteins were upregulated (>1.2 fold change) and 3 were downregulated (<0.8 fold change) in L1423. One important downregulated protein was lipoprotein 1569, a TLR2 agonist that promotes Th1 immunity. In the secretome, 12 proteins were upregulated while 1 was downregulated. The downregulated protein was Bsp22, a type III secretion system (T3SS) tip protein. Additionally, there was a trend of downregulation of T3SS effector proteins and other virulence factors. Five upregulated proteins in the secretome had transport/binding functions.
Conclusion: Expression of lipoprotein 1569, T3SS effector proteins and several transport/binding proteins appear to differentiate B. pertussis strains with high and low fitness. These differences may affect immune evasion, virulence and metabolism, and play a key role in the increased infectiveness of SNP cluster I.