Bordetella pertussis is the bacterium that causes pertussis, otherwise known asor whooping cough . Despite vaccination, incidence of pertussis cases have been growing over the last two decades. Current vaccines lack the ability to give long-lasting immunity and must be improved. Complement evasion molecules would make good candidates for vaccine components, because the complement system is essential in the killing of B. pertussis. The complement system is a first line of defense against colonization of bacteria in host tissue. Many bacteria employ complement inhibitors or attract human complement inhibitors to their surface. B. pertussis is no exception on this, however not much is known about the way B. pertussis evades the complement system . Prior to this study a few potential complement inhibitors of B. pertussis were identified. In this study we seek to characterize these proteins in a series of functional immune assays. Under these experimental conditions, we were not able to determine the function of the potential complement evasion molecules.
Bordetella pertussis is a Gram-negative bacterium and the causative agent of pertussis, also called whooping cough. Pertussis is a human-restricted disease of the respiratory tract and highly contagious ( en is dit zo? REF). Regular bouts of coughing produce airborne droplets through which B. pertussis can be transmitted (Jongerius et al. 2014). The disease was on the verge of eradication due to worldwide vaccination, but has been re-emerging in the last two decades. In 2008 there were 16 million cases of pertussis globally as estimated by the World Health Organisation. Possible explanations for the re-emergence are waning of immunity – since in the 1990s a different vaccine was introduced giving less enduring protection – or bacterial strain adaption (Mooi et al. 2014). Like many pathogens B. pertussis developed strategies to evade or repress the host response for successful colonization (REF). Little is known about the mechanisms by which B. pertussis escapes clearance by the complement system, a first line of defense in the immune response. Identification and characterization of these immune evasion molecules may lead to the discovery of new targets for anti-inflammatory drugs or new components for vaccines. Here, we try to characterize several potential complement inhibitors of B. pertussis, identified by phage display and genome analysis.
Bordetella pertussis virulence factors
B. pertussis expresses a variety of virulence factors that enable the bacteria to colonize the upper respiratory tract. The transcription of the majority of these virulence factors are regulated by the activity of the proteins BvgA and BvgS. BvgAS is a two-component system that controls gene expression in response to changing environmental conditions, such as temperature (Fedele et al. 2014). After inhalation the bacteria adhere to the ciliated epithelial cells of the larynx, trachea and bronchi, where they produce secreted toxins and membrane-bound molecules that contribute to the adherence (REF). The toxins damage the mucous layer of the respiratory tract, contributing to the pathogenesis of pertussis. For example tracheal cytotoxin (TCT) is proposed to cause ciliostasis, impairment of ciliary movement, which may explain the intense …
...(download the rest of the essay above)