Selected Publications
While most vaccines consisting of killed bacteria induce high serum antibody titers, they do not always confer protection as effective as that induced by infection, particularly against mucosal pathogens.
Bordetella pertussis and Bordetella parapertussis are closely related endemic human pathogens which cause whooping cough, a disease that is reemerging in human populations.
The genus Bordetella includes a group of closely related mammalian pathogens that cause a variety of respiratory diseases in a long list of animals (B. bronchiseptica) and whooping cough in humans (B. pertussis and B. parapertussis).
The evolution of Bordetella pertussis and Bordetella parapertussis from Bordetella bronchiseptica involved changes in host range and pathogenicity. Recent data suggest that the human-adapted Bordetella modified their interaction with host immune systems to effect these changes and that decreased stimulation of Toll-like receptor 4 (TLR4) by lipid A is central to this.
Bordetella pertussis causes whooping cough, an endemic respiratory disease that is increasing in prevalence despite vaccination efforts. Although host immunity is modulated by virulence factors of this pathogen, it is unclear what host factors are required to overcome their effects.
A recent resurgence in the number of cases of whooping cough, and other respiratory diseases caused by members of the bordetellae, in vaccinated populations has demonstrated the need for a thorough understanding of vaccine-induced immunity to facilitate more intelligent vaccine design.
Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection.
The threat of bioterrorist use of Bacillus anthracis has focused urgent attention on the efficacy and mechanisms of protective immunity induced by available vaccines.
Bordetella pertussis, a causative agent of whooping cough, expresses BrkA, which confers serum resistance, but the closely related human pathogen that also causes whooping cough, Bordetella parapertussis, does not.
Bordetella bronchiseptica is a gram-negative respiratory pathogen that infects a wide range of hosts and causes a diverse spectrum of disease. This diversity is likely affected by multiple factors, such as host immune status, polymicrobial infection, and strain diversity.
Pathogenic bacteria such as Bordetella bronchiseptica modulate host immune responses to enable their establishment and persistence; however, the immune response is generally successful in clearing these bacteria.
In a recent experiment, we found that mice previously infected with Bordetella pertussis were not protected against a later infection with Bordetella parapertussis, while primary infection with B. parapertussis conferred cross-protection.
We seek to understand the conditions favoring the evolution of acute, highly transmissible infections. Most work on the life-history evolution of pathogens has focused on the transmission-virulence trade-off.
Host immunity is a major driving force of antigenic diversity, resulting in pathogens that can evade immunity induced by closely related strains.
Despite excellent vaccine coverage in developed countries, whooping cough is a reemerging disease that can be caused by two closely related pathogens, Bordetella pertussis and B. parapertussis.
Despite the fact that closely related bacteria can cause different levels of disease, the genetic changes that cause some isolates to be more pathogenic than others are generally not well understood.
Pathogenic bacteria such as Bordetella bronchiseptica modulate host immune responses to enable their establishment and persistence; however, the immune response is generally successful in clearing these bacteria.
Modeling can help address questions about pathogen turnover, immune system responses, and pathogen spread within populations.
Although B. bronchiseptica efficiently infects a wide range of mammalian hosts and efficiently spreads among them, it is rarely observed in humans. In contrast to the many other hosts of B. bronchiseptica, humans are host to the apparently specialized pathogen B. pertussis, the great majority having immunity due to vaccination, infection or both.
The recognition of bacterial lipopolysaccharide (LPS) by host Toll-like receptor (TLR)4 is a crucial step in developing protective immunity against several gram negative bacterial pathogens.
Although the prevalence of Bordetella parapertussis varies dramatically among studies in different populations with different vaccination regimens, there is broad agreement that whooping cough vaccines, composed only of B. pertussis antigens, provide little if any protection against B. parapertussis.
