Hijacking of the Host’s Immune Surveillance Radars by Burkholderia pseudomallei

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.

Glycometabolism change during Burkholderia pseudomallei infection in RAW264.7 cells by proteomic analysis

“…Identifying the differentially expressed proteins of host cells and examining their interrelationships, such as enriched biological processes and pathways, will provide insight into the combined influence of B. pseudomallei on body function. There have been some studies explored the interaction between hosts and B. pseudomalle i 13 – 15 . For example, Loaiza et al predicted of host- pathogen protein interactions in B. pseudomallei and human in silico, discovered the host targets of the pathogen proteins and proteins that form T3SS and T6SS in B. pseudomallei.…”

TLR9 Negatively Regulates Intracellular Bacterial Killing by Pyroptosis in Burkholderia pseudomallei - Infected Mouse Macrophage Cell Line (Raw264.7)

“…The clinical manifestation of this infectious disease appears as abscess formation in visceral organs such as lung, liver, spleen, and soft tissues. Occasionally, infections can be acute, chronic, latent, and even progress to fatal sepsis ( 3 ). In the case of chronic infection, relapse of melioidosis patients is relatively common due to failure by the host to eradicate B. pseudomallei during the primary stages of infection, especially in the immunocompromised individuals.…”

“…In the case of chronic infection, relapse of melioidosis patients is relatively common due to failure by the host to eradicate B. pseudomallei during the primary stages of infection, especially in the immunocompromised individuals. The overall relapse rate can range between 15% and 30% in severe melioidosis ( 3 ). One of the unique features of B. pseudomallei is its ability to invade, survive, and multiply in both phagocytic and nonphagocytic cells ( 4 – 6 ).…”

Biofilm Signaling, Composition and Regulation in Burkholderia pseudomallei

“…Burkholderia pseudomallei (BP) is a gram-negative, environmental saprophyte predominately found in the soil and surface groundwater of endemic tropical and subtropical regions worldwide [ 1 , 2 ]. BP is the etiological agent of melioidosis, a life-threatening disease that accounts for approximately 89,000 deaths per year worldwide [ 2 - 6 ].…”

“…Diabetes mellitus remains a major risk factor for melioidosis; therefore, the rising global diabetes pandemic could further escalate the number of deaths attributed to melioidosis [ 2 ]. The virulence factors of BP include lipopolysaccharide (LPS), flagella, capsule, and type III secretory systems (TTSS), which have been identified to be involved in acute septicaemia and chronic melioidosis [ 1 , 7 ]. These virulence factors enhance bacterial survival and persistence across a wide range of hosts and facilitate evasion of the host’s immune response [ 1 , 7 ].…”