The lymphatic system as a potential mechanism of spread of melioidosis following ingestion of Burkholderia pseudomallei

Burkholderia pseudomallei is the causative agent of melioidosis, which is a Gram negative, facultative intracellular bacterium. Disease is prevalent in SE Asia and in northern Australia, as well as in other tropical and subtropical regions. Recently, there is an increasing awareness of the importance of bacterial ingestion as a potential route of infection, particularly in cases of unexplained origin of the disease. The marmoset is a New World Monkey (NWM) species that is being developed as an alternative NHP model to complement the more traditionally used Old World Monkeys (OWM). Models have been developed for the traditional routes of disease acquisition, subcutaneous and inhalational. This manuscript details the development and characterisation of an ingestion model of melioidosis. Dose-ranging study assessed the lethality of B. pseudomallei and disease progression was assessed by euthanizing animals at predetermined time points, 12, 36, 48 and 54 hours post-challenge. Challenge doses of greater than 6.2 x 10(6) cfu resulted in an acute, lethal, febrile disease. Following challenge the lung was the first organ, outside of the gastrointestinal tract, to become colonised. Enteritis (duodenitis, ileitis and/or jejunitis) was observed in sections of the small intestine from animals that succumbed to disease. However, the most severe pathological features were observed in the mesenteric lymph nodes from these animals. These findings are consistent with lymphatic draining as route of dissemination. Author summary Burkholderia pseudomallei is a bacteria that causes the disease melioidosis. Disease is usually caused by bacteria entering cuts in the skin or by breathing in the bacteria. But disease can also be caused by drinking water containing the bacteria, but this form of the disease is not well understand. Other researchers have looked at what happens when mice are given the bacteria via the mouth. This manuscripts looks at what happens when small monkeys, marmoset drink the bacteria. Different amounts of bacteria were given to the marmosets to determine how many bacteria are needed to cause disease. More than 6 million bacteria caused animals to have a fever and become sick enough to be euthanized. The bacteria travelled from the stomach to the intestine where there were small areas of swelling with lots of immune cells than caused damage to the tissue. The bacteria then went to the lungs really early in the disease and then spread to other parts of the body.

Automated summary

This paper discusses the ingestion model of melioidosis and found that challenge doses greater than 6.2 x 10^6 cfu result in acute, lethal, febrile disease. The study also revealed that the bacteria primarily spread through lymphatic draining.