Role for theBurkholderia pseudomalleiCapsular Polysaccharide Encoded by thewcbOperon in Acute Disseminated Melioidosis

Abstract

The capsular polysaccharide of Burkholderia pseudomallei is an essential virulence determinant that is required for protection from host serum cidal activity and opsonophagocytosis. In this study, the immune response directed against a B. pseudomallei capsule mutant (JW270) was investigated in an acute respiratory murine model. JW270 was significantly attenuated in this model (ϳ2 logs) to levels resembling those of avirulent Burkholderia thailandensis. At lethal doses, JW270 colonized the lung, liver, and spleen at levels similar to the wild-type strain levels and was found to trigger reduced pathology in the liver and spleen. Several cytokine responses were altered in these tissues, and importantly, the levels of gamma interferon were reduced in the livers and spleens of JW270-infected mice but not in the lungs. These results suggest that the capsular polysaccharide of B. pseudomallei is a critical virulence determinant in respiratory tract infections and that it is an important antigen for generating the Th1 immune response commonly observed in systemic melioidosis. Furthermore, the data suggest that host recognition of B. pseudomallei capsular polysaccharide in the lungs may not be as important to the disease outcome as the innate immune response in the peripheral organs.Burkholderia pseudomallei is a gram-negative pathogenic bacterium, the etiological agent of melioidosis, and a category B potential bioterrorism agent (29). B. pseudomallei is a saprophytic organism that can be isolated from standing water and moist soils in tropical areas worldwide; however, it is found primarily in areas of Southeast Asia and northern Australia where it is endemic. B. pseudomallei infects a wide range of both vertebrate and invertebrate hosts (24, 36, 39) and is considered an opportunistic pathogen which infects hosts directly from the environment rather than relying on zoonotic transfer mechanisms. The primary routes of infection include contamination of skin abrasions and inhalation of infectious particles. An increase in the incidence of respiratory melioidosis has been shown to be strongly associated with the monsoon season, as heavy rains and high winds are thought to aerosolize bacteria from the environment (9). Individuals with risk factors such as diabetes mellitus, thalassemia, renal impairment, or severe alcoholism are particularly susceptible to B. pseudomallei infection, and frequently infections in these risk groups progress to fatal septicemias (6).Several virulence determinants have been identified as factors that are critical to the virulence of B. pseudomallei in animal models; these factors include serine metalloprotease (MprA) (18, 33), type III secretion system cluster 3 (37, 44), type IV pilin (12), lipopolysaccharide (11), the Pml quorumsensing system (43), and capsular polysaccharide (1,26,27). Several metabolic and uncharacterized gene products are also required for pathogenesis of B. pseudomallei in animal models (8,21,25). Despite our understanding of the critical nature of these virulence determin...

Antibodies against In Vivo -Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei

“…The genes retained by B. mallei have an average identity of 99% at the nucleotide level with their B. pseudomallei orthologs, and of those, 650 have been proposed to form a core virulome based on comparative genomic analysis and sequence similarity to known virulence factors (28). Consistent with these in silico predictions, many virulome genes have been shown to specify key determinants in the pathogenesis of glanders and melioidosis, including lipopolysaccharide (LPS) (29,30), type 3 and type 6 secretion systems (31)(32)(33)(34)(35)(36)(37), and capsule (38)(39)(40)(41). In addition to their high level of genomic relatedness, the clinical and pathological manifestations of disease caused by B. mallei and B. pseudomallei are markedly similar.…”

Neutrophil Extracellular Traps Exhibit Antibacterial Activity against Burkholderia pseudomallei and Are Influenced by Bacterial and Host Factors

“…Addi-tionally, the Bsa T3SS influences the virulence of Burkholderia mallei (33). A polysaccharide capsule encoded by the wcb operon also plays a pivotal role in the pathogenesis of murine melioidosis (37). It has previously been reported that a polysaccharide capsule protects Streptococcus pneumoniae against entrapment in NETs (38); however, the role of capsule and of the Bsa T3SS in interactions with human PMN has received little study.…”

The Structure of Sedoheptulose-7-Phosphate Isomerase from Burkholderia pseudomallei Reveals a Zinc Binding Site at the Heart of the Active Site

“…infection; 15,16 acapsular mutants are strongly attenuated; 14,17,18 and the biosynthetic genes are absent in related, less pathogenic species. 14 In addition to providing a general defence against immune challenge, B.…”