Blood or serum exposure induce global transcriptional changes, altered antigenic profile, and increased cytotoxicity by classical Bordetellae

Authors: GESTAL, MONICA - University Of Georgia; RIVERA, ISRAEL - University Of Georgia; HOWARD, LAURA - University Of Georgia; DEWAN, KALYAN - University Of Georgia; SOUMANA, ILLIASSOU - University Of Georgia; DEDLOFF, MARGARET - University Of Georgia; Nicholson, Tracy; LINZ, BODO - University Of Georgia; HARVILL, ERIC - University Of Georgia

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/3/2018
Publication Date: 9/7/2018
Citation: Gestal, M.C., Rivera, I., Howard, L.K., Dewan, K.K., Soumana, I.H., Dedloff, M., Nicholson, T.L., Linz, B., Harvill, E.T. 2018. Blood or serum exposure induce global transcriptional changes, altered antigenic profile, and increased cytotoxicity by classical Bordetellae. Frontiers in Microbiology. 9:1969. https://doi.org/10.3389/fmicb.2018.01969.
DOI: https://doi.org/10.3389/fmicb.2018.01969

Interpretive Summary: The genus Bordetella contains nine designated species, three of which are so closely related that they are considered subspecies and are referred to as the "classical Bordetella". B. pertussis, B. parapertussis and B. bronchiseptica comprise the classical Bordetella. Although highly similar at the DNA sequence level, these bacteria vary in host specificity, severity of diseases, and their ability to cause acute versus chronic infection. B. bronchiseptica causes infections ranging from lethal pneumonia to asymptomatic respiratory carriage and chronically colonizes the respiratory tracts of various mammalian hosts. B. pertussis and B. parapertussis (hu), which are thought to have evolved independently from a B. bronchiseptica-like ancestor, are causative agents of pertussis or whooping cough in humans. Like all bacteria, the classical Bordetella sense and respond to a variety of environments outside and within their mammalian hosts. By causing inflammation and tissue damage, we reasoned that classical Bordetella are likely to encounter components of blood and/or serum during the course of a respiratory infection, and that detecting and responding to these signals would be advantageous. This study reports transcriptional changes that led to the production of new and novel antigens and enhanced disease causing traits, such as the ability to kill common host immune cells that occurred after exposure to blood or serum. The data in this report describes a new trait used by classical Bordetella to successfully cause respiratory diseases as well as persistence and/or transmission among their hosts. More importantly this study reports new antigens that could be further investigated for use in vaccines, which are critically needed due to the current re-emergence of pertussis and the lack of efficacious companion and domesticated animal vaccines.

Technical Abstract: The classical bordetellae sense and respond to a variety of environments outside and within their mammalian hosts. By causing inflammation and tissue damage, we reasoned that bordetellae are likely to encounter components of blood and/or serum during the course of a respiratory infection, and that detecting and responding to these would be advantageous. Therefore, we hypothesized that classical bordetellae have the ability to sense and respond to blood or serum. Blood or serum exposure resulted in substantial transcriptional changes in Bordetella bronchiseptica, including enhanced expression of many virulence-associated genes. Exposure to blood or serum additionally elicited production of multiple antigens not otherwise detectable, and led to increased bacterial cytotoxicity against macrophages. Transcriptional responses to blood/serum were observed in a Bvg- phase-locked mutant, indicating that the response is not dependent on a functional BvgAS system. Similar transcriptional responses to blood/serum were observed for the other classical bordetellae, Bordetella pertussis and Bordetella parapertussis. These data suggest the classical bordetellae respond to signals present in blood and serum by changing their behavior in ways that likely contribute to their remarkable success, via effects on pathogenesis, persistence and/or transmission between hosts.