Abstract
The genus Burkholderia contains over 80 different Gram-negative species including both plant and human pathogens, the latter of which can be classified into one of two groups: the Burkholderia pseudomallei complex (Bpc) or the Burkholderia cepacia complex (Bcc). Bpc pathogens Burkholderia pseudomallei and Burkholderia mallei are highly virulent, and both have considerable potential for use as Tier 1 bioterrorism agents; thus there is great interest in the development of novel vaccines and therapeutics for the prevention and treatment of these infections. While Bcc pathogens Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia cepacia are not considered bioterror threats, the incredible impact these infections have on the cystic fibrosis community inspires a similar demand for vaccines and therapeutics for the prevention and treatment of these infections as well. Understanding how these pathogens interact with and evade the host immune system will help uncover novel therapeutic targets within these organisms. Given the important role of the complement system in the clearance of bacterial pathogens, this arm of the immune response must be efficiently evaded for successful infection to occur. In this review, we will introduce the Burkholderia species to be discussed, followed by a summary of the complement system and known mechanisms by which pathogens interact with this critical system to evade clearance within the host. We will conclude with a review of literature relating to the interactions between the herein discussed Burkholderia species and the host complement system, with the goal of highlighting areas in this field that warrant further investigation.
Highlights
Expression of surface proteins that recruit complement regulators is a well-known mechanism of host immune evasion used by a wide variety of pathogens (Table 1)
The LPS- and capsule-independent serum resistance phenotypes observed by Burkholderia indicates that these bacteria bind one or more complement regulators to evade clearance by the host immune system
While recruitment of vitronectin contributes to serum resistance of pathogens, its mechanism of action involves inhibiting membrane attack complex formation
Summary
B. pseudomallei is the causative agent of melioidosis, a disease originally observed by physicians Alfred Whitmore and C.S. Krishnaswami at Rangoon General Hospital in what is Myanmar (Whitmore and Krishnaswami, 1912). Chronic melioidosis makes up 11% of cases and is characterized as a less severe disease with symptoms persisting for over 2 months (Currie et al, 2010). While cutaneous inoculation is the most common route of infection, aerosol delivery of B. pseudomallei significantly increases its virulence, with a 99-fold increase in disease potential observed in mice (Warawa, 2010). For this reason, inhalation is considered the most lethal route of infection. Regardless, due to the potential for this organism to pose a severe threat to human health and safety, B. pseudomallei is listed as a Tier 1 select agent and must be worked with under biosafety level 3 (BSL-3) conditions
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