Editor's Spotlight: Vaccination and evolutionary parallels between two strains of whooping cough bacteria

Posted on December 2, 2025   by Jesse Shapiro

In this Editor’s Spotlight, Senior Editor, Jesse Shapiro, takes a closer look at this featured paper ‘No innocent bystanders: pertussis vaccination and evolutionary parallelisms between Bordetella parapertussis and Bordetella pertussis’, recently published in Microbial Genomics. 
 

Vaccines are usually very specific, designed to train our immune systems against a particular pathogen. In some cases, less specific vaccines are desirable – think of a pan-coronavirus vaccine – but are often challenging to develop because they must target pathogen features that are conserved across species. But sometimes, vaccines target a broader range of species than anticipated. Such is the case for vaccines against Bordetella pertussis (Bp), the bacteria causing whooping cough. Bouchez and colleagues, writing in Microbial Genomics, describe compelling evidence that the Bp vaccine is selecting for parallel evolutionary changes in a related bacteria, Bordetella parapertussis (Bpp). In their comparative genomic study spanning a decade of bacterial evolution, they make the case that Bpp is a rare example of an ‘innocent bystander’, affected by a vaccine intended to target a different species.

Parallel evolution is a hallmark of natural selection which typically occurs when different lineages or species independently acquire the same mutation in response to the same selective pressure. Bouchez and co-authors show a clear example: after the rollout of vaccines containing a Bp protein called pertactin, they documented a shift in the Bpp population toward pertactin-deficient lineages. These pertactin-deficient lineages contained 18 different parallel mutations that disrupt pertactin expression. Together, these observations strongly suggest that Bpp is evolving to lose or reduce pertacting expression, mirroring similar documented changes in Bp as it evolves in response to the vaccine.

But are Bp and Bpp really different species? They are certainly distinct lineages, forming clearly separate groups on a phylogenetic tree, but they share >98% average nucleotide identity across their genomes, as shown in a previous study by senior author Sylvain Brisse and members of his team (Bridel et al., Nature Communications 2022). By standard genetic criteria, this would place Bp and Bpp within the same species. They also share a very similar niche in the human respiratory tract and likely compete in many dimensions of niche space. Notably Bpp encodes but does not express genes for pertussis toxin, suggesting it may be less virulent and explaining why it is a less frequent cause of whooping cough than Bp. Disentangling the extent of niche overlap between these two species, or sublineages of the same species, remains a fascinating avenue for future research.

It is not surprising to witness pathogen evolution in response to a vaccine. We have seen this happen during the rollout of pneumococcal vaccines over the past few decades, and vaccines are continuously updated to target more serotypes. Flu and COVID-19 vaccines are also updated annually. More surprising, perhaps, is an evolutionary response in a pathogen not intentionally targeted by the vaccine. Upon reflection, and certainly upon considering the study by Bouchez et al., perhaps this ‘bystander effect’ is more common than expected. Their study raises exciting new questions. How common are bystander effects? Would we find more examples if we looked? Are they more common among closely-related species or lineages like Bp and Bpp? Are there unintended consequences of bystander evolution, perhaps pushing bystander species in unexpected evolutionary directions? I look forward to learning the answers to these questions, if not as an active researcher, then certainly as an interested bystander.