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

PLoS Negl Trop Dis. 2021 Feb 22;15(2):e0009016. doi: 10.1371/journal.pntd.0009016. eCollection 2021 Feb.

Abstract

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 106 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Burkholderia pseudomallei / pathogenicity
  • Burkholderia pseudomallei / physiology*
  • Callithrix
  • Disease Models, Animal
  • Enteritis / microbiology
  • Female
  • Lung / microbiology
  • Lymph Nodes / microbiology
  • Lymph Nodes / pathology
  • Lymphatic System / microbiology*
  • Male
  • Melioidosis / microbiology
  • Melioidosis / pathology*

Grants and funding

This work was funded by the US Food and Drug Administration under a Broad Agency Announcement, contract number HHSF223201510066C. MN received the funding for this work. The sponsors reviewed study design but had no role in data collection and analysis, decision to publish, or preparation of the manuscript.