Prophylactic Use of Ganoderma lucidum Extract May Inhibit Mycobacterium tuberculosis Replication in a New Mouse Model of Spontaneous Latent Tuberculosis Infection

Abstract

A mouse model of spontaneous latent tuberculosis infection (LTBI) that mimics LTBI in humans is valuable for drug/vaccine development and the study of tuberculosis. However, most LTBI mouse models require interventions, and a spontaneous LTBI mouse model with a low bacterial load is difficult to establish. In this study, mice were IV-inoculated with 100 CFU Mycobacterium tuberculosis H37Rv, and a persistent LTBI was established with low bacterial loads (0.5~1.5log10 CFU in the lung; < 4log10 CFU in the spleen). Histopathological changes in the lung and spleen were mild during the first 20 weeks post-inoculation. The model was used to demonstrate the comparative effects of prophylactic and therapeutic administration of Ganoderma lucidum extract (spores and spores lipid) in preventing H37Rv replication in both lung and spleen. H37Rv was inhibited with prophylactic use of G. lucidum extract relative to that of the untreated control and therapy groups, and observed in the spleen and lung as early as post-inoculation week 3 and week 5 respectively. H37Rv infection in the therapy group was comparable to that of the untreated control mice. No significant mitigation of pathological changes was observed in either the prophylactic or therapeutic group. Our results suggest that this new LTBI mouse model is an efficient tool of testing anti-tuberculosis drug, the use of G. lucidum extract prior to M. tuberculosis infection may protect the host against bacterial replication to some extent.

Animal Models for Tuberculosis in Translational and Precision Medicine

“…Active TB models can be prepared in a variety of experimental animals for drug and vaccine evaluation, but it takes at least 2 months to complete in vivo research and evaluation (Gouveia et al, 2013 ; Izzo et al, 2015 ; Zhan et al, 2015 ; Conde et al, 2016 ; Swanson et al, 2016 ). This lengthy experimental time hinders the development of new drugs and vaccines.…”

“…This requires a huge number of experimental animals and increases bio-safety risks. There is also inter-individual variation within experimental groups (Zhan et al, 2015 ). These problems can be solved by in vivo monitoring technology.…”

Mice continue to be a good model for preliminary assessment of tuberculosis vaccine candidates

“…For tuberculosis studies, nowadays is accepted to consider as relevant surrogate markers, the bacterial load, pathological changes in the lung, reducing symptoms and relapse to active disease or damage associated with it. [1][2][3] As mentioned before, there are different animal models applied for research in the tuberculosis field, and although none of them completely mimics all aspects occurring during infection in human beings, all these models provide valuable information regarding particular stages of infection. Their use allows to study granuloma formation, liquefaction, cavity formation, and hematogenous spread to other organs from the lungs.…”

The development and application of Laboratory Animal Science in China

“…[9][10][11][12] In order to improve the reliability and repeatability of animal experimental results, the standardization of animal model development and evaluation technology in infectious diseases has been performed, which has solved the problem of poor reproducibility of animal experiment results. 13,14 Based on the animal model system for the whole process of Finally, the development of the Gene Mine offers the potential for many new animal models of disease to be developed. Harnessing the genetic repertoire of the mouse species, the Gene Mine consists of dozens of recombinant inbred strains, resembling a large pedigree of dozens of "cousins" descended from eight "great-grandparents".…”