Academic literature on the topic 'Dermonecrotic toxin'

Bordetella species express virulence factors that enable host immune evasion and establishment of prolonged respiratory infection. Upon interaction with ciliated cells of the host upper airway, bordetellae are subjected to antimicrobial reactive nitrogen species (RNS) and reactive oxygen species (ROS) as part of the host innate immune defense. I hypothesized that RNS and ROS have anti-Bordetella activity at physiologically relevant concentrations. In a novel in vitro assay, B. bronchiseptica exposure to prototypical redox active species revealed toxicity at physiologically relevant (nM-μM) concentrations. Antimicrobial synergy was observed when individual redox active species were applied in combination. Additionally, there was increased bacteriostatic activity of nitric oxide towards Bordetella relative to hydrogen peroxide. Analysis of B. bronchiseptica mutant strains unable to respond to physiological stimuli via the two-component virulence control system BvgAS identified a protective role for BvgAS in the Bordetella redox stress response. The observation that RNS and ROS produced by airway epithelial cells have anti-Bordetella activity at physiologically relevant concentrations encourages further analysis of how manipulation of redox active species in the airway can be utilized to combat airway infection. Species of the Bordetella genus express a conserved virulence factor, dermonecrotic toxin (DNT), that in purified form can target host cell cytoskeletal regulators. However, DNT is not released from cultured bacteria, and no mechanism for bacteria to host transfer has been described. I hypothesized that loss of DNT expression affects bacterial physiological processes. Comparison of wild type B. bronchiseptica and a DNT mutant strain revealed an altered proteome that included several proteins associated with bacterial metabolism. In vitro, loss of DNT expression resulted in increased sensitivity to physiological stress. Comparison of wild type and DNT mutant B. bronchiseptica interactions with primary cultured rabbit tracheal epithelial cells did not reveal a function for DNT in host cell actin cytoskeletal rearrangement during the B. bronchiseptica-host interaction. It is suggested that DNT is conserved across the Bordetella genus because of its effects on bacterial physiology. This is a novel perspective on a Bordetella factor under BvgAS control and may have implications for understanding similar necrotizing factors from other virulent bacteria.

Bordetella pertussis is a strictly human pathogen colonizing the upper respiratory tract, causing a respiratory disease known as whooping cough or pertussis. The introduction of whole-cell vaccines and acellular vaccines, resulted in a significant reduction in the incidence of disease and reduce the fatalities associated with infection. However, epidemiological data show a significant increase in the incidence of the disease in recent decades. The increasing incidence is mainly attributed to the transition from the whole- cell vaccine to an acellular vaccine. Based on research from recent years has shown that acellular vaccines have many drawbacks, and it is therefore necessary to change the vaccination strategy. One possible solution to the situation is the development of a new generation of whole-cell vaccines with reduced reactogenicity. The new whole-cell vaccine was prepared by a genetically modified B. pertussis strain. B. pertussis was modified using allelic exchange to develop strain encoding enzymatically inactive pertussis toxin, modified lipid A and lacking dermonecrotic toxin. This combination of genetic modifications in mice led to a decrease in reactogenicity test vaccine in vivo. In case of intranasal infection whole-cell vaccine containing genetically modified strain is providing...