Monoclonal antibodies opsonise Burkholderia and reduce intracellular actin tail formation in a macrophage infection assay.

Melioidosis is a neglected tropical disease caused by the bacterium Burkholderia pseudomallei. The bacterium is intrinsically resistant to various antibiotics and melioidosis is therefore difficult to treat successfully without relapse in infection. B. pseudomallei is an intracellular pathogen, and therefore to eradicate the infection, antimicrobials must be able to access bacteria in an intracellular niche. This study assessed the ability of a panel of monoclonal antibodies to opsonise Burkholderia species and determine the effect that the antibody has on bacterial virulence in vitro. Murine macrophage infection assays demonstrated that monoclonal antibodies to the capsule of B. pseudomallei are opsonising. Furthermore, one of these monoclonal antibodies reduced bacterial actin tail formation in our in vitro assays, indicating antibodies could reduce the intracellular spread of B. thailandensis. The data presented in this paper demonstrates that monoclonal antibodies are opsonising and can decrease bacterial actin tail formation, thus decreasing their intracellular spread. This data has informed selection of an antibody for development of an antibody-antibiotic conjugate for melioidosis. Importance statement Melioidosis is difficult to treat successfully due to the bacterium being resistant to many classes of antibiotics, therefore available therapeutic options are limited. New and improved therapies are urgently required to treat this disease. Here we have investigated the potential of monoclonal antibodies to target this intracellular pathogen. We have demonstrated that monoclonal antibodies can target the bacterium, increase uptake into macrophages and reduce actin tail formation required by the bacterium for spread between cells. Through targeting the bacterium with antibodies we hope to disarm the pathogen, reducing the spread of infection. Ultimately we aim to use an opsonising antibody to deliver antibiotics intracellularly by developing an antibody-antibiotic conjugate therapeutic for melioidosis.