A marine sponge-associated mycobacterium closely related toMycobacterium tuberculosis

Abstract

AbstractReconstructing the evolutionary origins ofMycobacterium tuberculosis, the causative agent of human tuberculosis, has helped identify bacterial factors that have led to the tubercle bacillus becoming such a formidable human pathogen. Here we report the discovery and detailed characterization of an exceedingly slow growing mycobacterium that is closely related toM. tuberculosisfor which we have proposed the species nameMycobacterium spongiaesp. nov., (strain ID: FSD4b-SM). The bacterium was isolated from a marine sponge, taken from the waters of the Great Barrier Reef in Queensland, Australia. Comparative genomics revealed that, after the opportunistic human pathogenMycobacterium decipiens,M. spongiaeis the most closely related species to theM. tuberculosiscomplex reported to date, with 80% shared average nucleotide identity and extensive conservation of keyM. tuberculosisvirulence factors, including intact ESX secretion systems and associated effectors. Proteomic and lipidomic analyses showed that these conserved systems are functional in FSD4b-SM, but that it also produces cell wall lipids not previously reported in mycobacteria. We investigated the virulence potential of FSD4b-SM in mice and found that, while the bacteria persist in lungs for 56 days after intranasal infection, no overt pathology was detected. The similarities withM. tuberculosis, together with its lack of virulence, motivated us to investigate the potential of FSD4b-SM as a vaccine strain and as a genetic donor of the ESX-1 genetic locus to improve BCG immunogenicity. However, neither of these approaches resulted in superior protection againstM. tuberculosischallenge compared to BCG vaccination alone. The discovery ofM. spongiaeadds to our understanding of the emergence of theM. tuberculosiscomplex and it will be another useful resource to refine our understanding of the factors that shaped the evolution and pathogenesis ofM. tuberculosis.