Interaction betweenBurkholderia pseudomalleiand the Host Immune Response: Sleeping with the Enemy?

Abstract

Melioidosis is an infectious disease endemic in tropical and subtropical areas but is most often described in Southeast Asia and northern Australia. It has increasingly gained attention in the Western Hemisphere because of its potential use as a biological weapon. Progress in our understanding of the virulence mechanisms of Burkholderia pseudomallei, the causative agent, has provided clues to the pathogenesis of the disease. The bacterium can remain latent in the body for long periods of time and also possesses mechanisms to evade the host immune response. The complex spectrum of clinical manifestations resulting from infection could reflect the various outcomes after the host immune response encounters the bacteria. The use of appropriate animal models of susceptibility will likely shed light on what determines the development of an acute, chronic, or latent infection.

Burkholderia pseudomalleiIsocitrate Lyase Is a Persistence Factor in Pulmonary Melioidosis: Implications for the Development of Isocitrate Lyase Inhibitors as Novel Antimicrobials

“…In addition to these clinical similarities, we have described significant similarities between the pathological changes associated with tuberculosis and those seen in a chronic melioidosis animal model that we have developed, which include multiple-granuloma formation (36). Besides the similar lung pathology, both B. pseudomallei and M. tuberculosis infections can enter into a dormant phase, where there are no signs of infection (8,24).…”

“…Little is known about latent B. pseudomallei infections, but the striking similarity to M. tuberculosis infections has led to speculations that these organisms use similar pathways to produce latency (8). For example, both M. tuberculosis and B. pseudomallei are able to survive for long periods of time in a dormant or nondividing state in vitro (20,38), and it has been hypothesized that these organisms may remain in a similar state during latent pulmonary infections.…”

Burkholderia pseudomalleikillsCaenorhabditis elegansthrough virulence mechanisms distinct from intestinal lumen colonization

“…1 When acquired by humans and animals, B. pseudomallei can cause melioidosis, a life-threatening disease that, to this day, still presents a danger to most parts of the tropics. 2 Decades of research on B. pseudomallei has only revealed how versatile this pathogen is, for example, it can (1) infect a multitude of organisms and invade a wide range of cell types, 3,4 (2) result in a broad spectrum of clinical manifestations, 5 (3) resist many clinical antimicrobials 6 and (4) survive extremely harsh environmental conditions. 7 Yet, the molecular mechanisms by which B. pseudomallei evades or modulates host immune responses remain elusive.…”

Burkholderia pseudomallei Capsule Exacerbates Respiratory Melioidosis but Does Not Afford Protection against Antimicrobial Signaling or Bacterial Killing in Human Olfactory Ensheathing Cells

“…Staphylococcus aureus infection (64). Gan (65) suggested that the development of acute melioidosis is due not to a lack but rather an excess of inflammation and a failure of regulatory mechanisms. We observed increased levels of antiinflammatory cytokines at 48 h p.i.…”