Evidence for Multi-Organ Infection During Experimental Meningococcal Sepsis due to ST-11 Isolates in Human Transferrin-Transgenic Mice

Abstract

The description of invasive meningococcal disease that is provoked by Neisseria meningitidis (Nm) is frequently restricted to meningitis. However, a wide panel of clinical presentations can be encountered including severe forms with intense inflammatory reaction leading to multi-organ failure. Several human factors are involved in the development of invasive infections such as transferrin, factor H or CEACAM1. In this study, we used an experimental meningococcal infection in transgenic mice expressing the human transferrin to show multi-organ infection. Mice were infected by an intraperitoneal injection of bacterial suspension (1.5 × 107 colony-forming unit/mouse) of a bioluminescent serogroup C strain belonging to the clonal complex ST-11. Dynamic imaging and histological analysis were performed. The results showed invasion of tissues by Nm with bacteria observed, outside blood vessels, in the kidneys, the heart and the brain as well as skin involvement. These data further support the systemic aspect of invasive meningococcal disease with involvement of several organs including skin as in humans. Thus, our model can be used to study severe forms of meningococcal invasive infections with multi-organ failure.

Investigating the importance of surface exposed loops in the gonococcal HpuB transporter for hemoglobin binding and utilization

“…However, the sequence conservation of Hbs from the different species is very high, consistent with the ability of the HpuAB system to recognize multiple forms of Hb from distinct animal species. While transgenic mouse models of disease are being developed (59, 60), to assess the contributions of TbpAB and the zinc transport systems to virulence, this may not be necessary for the HpuAB system as the mouse Hb can presumably be employed as an iron and heme source if it is available during experimental infections.…”

Vertebrate and Invertebrate Animal and New In Vitro Models for Studying Neisseria Biology

“…Another transgenic mouse model expresses the human transferrin receptor, and intraperitoneal infection of these animals has allowed the process of meningococcal invasion of the blood, blood vessels, kidneys, heart, brain and skin to be studied [ 208 ]. Microarray transcriptional profiling of blood and brain samples from infected transgenic mice showed expression of genes encoding acute phase proteins, chemokines, cytokines and IL-1 receptor-associated kinase-3 (IRAK-3) [ 209 ].…”