Date Published: March 28, 2019
Publisher: Public Library of Science
Author(s): Kalyan K. Dewan, Eric T. Harvill, Jorn Coers.
The closest phylogenetic neighbors of B. pertussis are B. parapertussis and B. bronchiseptica, the three species sharing genetic similarities up to 99% in large sections of the conserved genomic regions, and together commonly referred to as the Classical Bordetellae . The current view of their natural history, based on phylogenetic assessment, is that the ancestral progenitor of the Classical Bordetellae was likely to be similar to the broad host range B. bronchiseptica. The human-restricted B. pertussis and B. parapertussis emerged independently from it [5,6], as did another lineage, also called B. parapertussis (Bppov) that only infects sheep .
Evidence of likely environmental origins of the ancestral lineage of pathogenic Bordetella species led to a recent study that uncovered two independent and complete but intersecting transmission cycles for B. bronchiseptica (Fig 1) . One cycle (Bvg+) involves circulating as a respiratory pathogen and/or commensal among a broad range of domesticated and wild mammals. The other life cycle (Bvg−) enables a stable association between the bacteria and predatory amoeba in the extra-host environment, allowing B. bronchiseptica to grow and disperse to new locations along with the amoebae. Experiments have also shown that modest numbers of amoeba and spores that harbor the bacteria can colonize mammalian hosts via drinking water, indicative of the ability of B. bronchiseptica to switch between these alternating life cycles in the wild . Occasional spillover from one life cycle to the other creates an observable “meta” cycle of transmission that can explain both the Bvg paradox and some of the remarkable abilities of the various Bordetella species .
The remarkable ability to subvert phagocytic amoebae of the environment is likely to involve many different molecular “tools” that could contribute to the ability to cause opportunistic infections in mammals. Transmission between animal hosts is facilitated by pathogenic symptoms such as cough or rhinorrhea. But a host population must be sufficiently dense and large to maintain a constant, uninterrupted chain of transmission that lasts over many generations, allowing for extended evolution, specialization, and speciation. Ancient wild animal populations were relatively sparse with less opportunity for sustained transmission chains, so a closed life cycle only in animals was doomed for extinction, hence the “meta” cycle was maintained. But relatively recent increases in density and size of various animal populations, a profound effect of the rise of the Anthropocene, would predictably affect the opportunity for emergence of pathogenic Bordetella species with closed life cycles. In this light, the emergence and/or expansion of Bordetella species as pathogens of individual host animals may be viewed as the consequence of human activities such as animal herding, poultry farming, and urbanization.
Repeated speciation correlating with host restriction is observed in several instances amongst both the Classical and non–Classical Bordetellae, as well as in a wide range of different animal hosts (Fig 2). In addition to B. pertussis and B. parapertussisHu found transmitting only among humans and B. parapertussisOv only among sheep, the nonclassical species B. avium and B. hinzii have been found naturally circulating among birds, whereas the newly discovered species, B. pseudohinzii, has been found naturally circulating among rodents, including laboratory mice . The phylogenetic relationships of these species  indicate that such host-specialized transmission cycles have arisen from a common ancestral metacycle in the environment.
The search for the origins of B. pertussis has revealed several potential progenitor Bordetella species in the environment . Their presence in widely varying environmental niches, such as contaminated soil and surfaces of oil paintings makes it clear that non–Classical Bordetellae are not stagnant and/or vestigial remnants of prior states but vibrant and aggressively evolving organisms that are well adapted and successful in different niches. There are anecdotal reports of nonclassical Bordetella species being isolated from humans (B. holmesii, B. hinzii, B. trematum, B. bronchialis, B. flabilis, B. sputigena, B. ansorpii, B. petrii) [20–24]. Such clinical cases are often described as instances of opportunistic infections associated with immune-deficient states. However, given the diversity of opportunistic pathogens that have been observed, and the likelihood that there is substantial under-reporting, the true numbers or range of species that humans host can only be much larger. Based on a broader view of the natural history of Bordetella species, these cases could be described as spillover from various established transmission cycles in mammals or the environment. Though capable of partially overcoming mammalian host defenses using mechanisms likely acquired in the environment, most appear to lack specialized mechanisms to efficiently transmit among humans. One likely hurdle they face is the substantial current vaccine- or infection-induced immunity to B. pertussis. If it is a goal to eliminate B. pertussis from human populations , then it should be considered that other Bordetella species may be emerging from diverse sources, including potential metacycles of transmission in the environment. Anthropogenesis of increasingly high-density animal populations could affect the ongoing evolution of virulence in these sources of zoonoses.