Abstract
Burkholderia pseudomallei (B. pseudomallei) causes melioidosis, a potentially fatal disease for which no licensed vaccine is available thus far. The host-pathogen interactions in B. pseudomallei infection largely remain the tip of the iceberg. The pathological manifestations are protean ranging from acute to chronic involving one or more visceral organs leading to septic shock, especially in individuals with underlying conditions similar to COVID-19. Pathogenesis is attributed to the intracellular ability of the bacterium to ‘step into’ the host cell’s cytoplasm from the endocytotic vacuole, where it appears to polymerize actin filaments to spread across cells in the closer vicinity. B. pseudomallei effectively evades the host’s surveillance armory to remain latent for prolonged duration also causing relapses despite antimicrobial therapy. Therefore, eradication of intracellular B. pseudomallei is highly dependent on robust cellular immune responses. However, it remains ambiguous why certain individuals in endemic areas experience asymptomatic seroconversion, whereas others succumb to sepsis-associated sequelae. Here, we propose key insights on how the host’s surveillance radars get commandeered by B. pseudomallei.
Highlights
Melioidosis is a systemic infectious disease caused by Burkholderia pseudomallei (B. pseudomallei), a Gram-negative environmental saprophyte commonly found in wet soils and contaminated waters of endemic areas [1]
B. pseudomallei appears to escape from phagocytosis via production of a capsular polysaccharide (CPS), which abridges the deposition of C3b on their surfaces [42]
Based on the combined in vivo experiments, it was concluded that in B. pseudomallei SCVs infection, Programmed death 1 (PD-1) was upregulated on both adaptive and innate immune cells, whereas PD-1 up-regulation only was observed in B. pseudomallei wild types (WTs) infection [114, 115]
Summary
Melioidosis is a systemic infectious disease caused by Burkholderia pseudomallei (B. pseudomallei), a Gram-negative environmental saprophyte commonly found in wet soils and contaminated waters of endemic areas [1]. Infections can remain sub-clinical, while others can develop acute or chronic disease or can even progress to fatal sepsis [12]. Symptoms extending for ≥2 months is defined as chronic melioidosis that usually occurs in ~10% of infected individuals [10, 13]. Melioidosis relapse is relatively common due to failure by the host to eradicate B. pseudomallei during the primary stages of infection, especially in the immunocompromised, and even after prolonged antimicrobial therapy. Dormant sub-clinical infections are recognized in several cases, whereby it could stimulate to cause disease, typically in association with an inter-current illness, classically with lung disease, surgical procedure or trauma. Alterations in the virulence of infecting strains together with host immune-competence could likely contribute to disease prognosis [18]
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