Serum From Melioidosis Survivors Diminished Intracellular Burkholderia pseudomallei Growth in Macrophages: A Brief Research Report

Abstract

Melioidosis is a neglected tropical disease with high mortality rate. It is caused by the Gram-negative, CDC category B select agent Burkholderia pseudomallei ( B. ps ) that is intrinsically resistant to first-line antibiotics. An antibody-based vaccine is likely to be the most effective control measure. Previous studies have demonstrated significant mechanistic roles of antibodies in protection against death in animal models, but data from human melioidosis is scarce. Herein, we used in-vitro antibody-dependent cellular phagocytosis and growth inhibition assays to assess the mechanism of protective antibodies in patients with acute melioidosis. We found that serum from patients who survived the disease enable more live B. ps to be engulfed by THP-1 derived macrophages (median 1.7 × 10 3 CFU/ml, IQR 1.1 × 10 3 -2.5 × 10 3 CFU/ml) than serum from patients who did not survive (median 1.2 × 10 3 CFU/ml, IQR 0.7 × 10 3 -1.8 × 10 3 , p = 0.02). In addition, the intracellular growth rate of B. ps pre-opsonized with serum from survivors (median 7.89, IQR 5.58–10.85) was diminished when compared with those with serum from non-survivors (median 10.88, IQR 5.42–14.88, p = 0.04). However, the difference of intracellular bacterial growth rate failed to reach statistical significance when using purified IgG antibodies ( p = 0.09). These results provide new insights into a mechanistic role of serum in protection against death in human melioidosis for antibody-based vaccine development.

Functional Activities of O-Polysaccharide and Hemolysin Coregulated Protein 1 Specific Antibodies Isolated from Melioidosis Patients

“…Our ADCP results in this study confirmed findings from a previous report by Chaichana et al that serum from melioidosis patients can enhance opsonization of B. pseudomallei in a THP-1 cell derived macrophage model ( 25 ). Although a follow-up study by Chaichana et al demonstrated that high levels of total IgG2 and the expression of FcγRIIa-H/R131, an intermediate-affinity IgG2 receptor, were associated with protection against death in acute melioidosis ( 26 ), they did not identify the specific target antigen for IgG2 as they used whole cells of B. pseudomallei in their assay.…”

“…A study in human melioidosis showed a lower mortality rate was associated with seropositivity against crude B. pseudomallei antigen preparations ( 23 ). We previously reported an association of survival with high levels of IgG against OPS and Hcp1 in melioidosis patients ( 18 , 24 ) suggesting a potential functional role for these antibodies in protection against disease ( 25 ). In addition, Chaichana et al demonstrated that serum from survivors of melioidosis enhanced bacterial uptake compared to serum from nonsurvivors ( 25 ).…”

“…We previously reported an association of survival with high levels of IgG against OPS and Hcp1 in melioidosis patients ( 18 , 24 ) suggesting a potential functional role for these antibodies in protection against disease ( 25 ). In addition, Chaichana et al demonstrated that serum from survivors of melioidosis enhanced bacterial uptake compared to serum from nonsurvivors ( 25 ). The same study demonstrated that purified IgG against whole-cell antigen promotes antibody-dependent cellular phagocytosis (ADCP).…”

Melioidosis Patient Survival Correlates With Strong IFN-γ Secreting T Cell Responses Against Hcp1 and TssM

“…Serum antibodies against B. pseudomallei cell surface polysaccharides and proteins are detectable in acute melioidosis infections (26,28,(42)(43)(44). There is some evidence in human and animal models that antibody responses play a key role in protection against melioidosis (14,15,26,31,45,46). Our previous studies showed that melioidosis patients who lived in endemic areas had high IgG responses to Hcp1 and Opolysaccharide (28,31,47).…”

Leptospirosis and Coinfection: Should We Be Concerned?

“…Bukholderia pseudomallei is a soil and water surface bacterium found in tropical areas that causes melioidosis after exposure to contaminated water or soils [114]. Melioidosis has been reported in Malaysia and other endemic countries such as Brazil [124], Australia [125], India [126] and Thailand [127]. Infection with B. pseudomallei is most commonly associated with an inoculating injury, ingestion, or inhalation of aerosolized bacteria and occurs more frequently in the wet season or following extreme weather events such as tropical storms.…”