Abstract and Introduction
Mycobacterium tuberculosis, an etiologic agent of tuberculosis, exacts a heavy toll in terms of human morbidity and mortality. Although an ancient disease, new strains are emerging as human population density increases. The emergent virulent strains appear adept at steering the host immune response from a protective Th1 type response towards a Th2 bias, a feature shared with some pathogenic fungi. Other common characteristics include infection site, metabolic features, the composition and display of cell surface molecules, the range of innate immune receptors engaged during infection, and the ability to form granulomas. Literature from these two distinct fields of research are reviewed to propose that the emergent virulent strains of M. tuberculosis are in the process of convergent evolution with pathogenic fungi, and are increasing the prominence of conserved traits from environmental phylogenetic ancestors that facilitate their evasion of host defenses and dissemination.
The etymology of 'mycobacterium' reflects early observations that the growth characteristics and morphology of the bacterium resemble that of fungi. Recent investigations have revealed this likeness extends to multiple characteristics, particularly relating to pathogenesis. Members of the mycobacterium complex, that is, bacteria of the genus Mycobacterium that can cause disease in humans, have long been considered a peculiarity among bacteria, neither Gram positive nor Gram negative, and very slow growing. Their distinctive lipid-rich cell wall structure has set them apart from most bacteria, and for pathogenic mycobacteria such as M. tuberculosis it is key for its growth, viability and virulence characteristics.
Although M. tuberculosis has a highly conserved genome, new strains are emerging, generating diversity in virulence and clinical outcome.[2–4] Recent advances in gene sequencing technology have enabled, for the first time, large-scale comparisons to be made between the genomes of M. tuberculosis from diverse origins, and have revealed important insights into the phylogeny and global spread of this pathogen. The major genetic lineages of M. tuberculosis occupy different geographical regions and have evolved varying degrees of virulence.[5–7] Thousands of single-nucleotide polymorphisms (SNPs) have been identified among clinical isolates, some of which have been linked with important phenotypes such as resistance to antibiotics.[8–11] Differences have also been identified among mycobacterial cell wall glycolipids[12–14] and secreted proteins such as those of the PE/PPE family. This information has contributed to the emergence of a broader concept: a working hypothesis that the more virulent strains, especially outbreak strains of M. tuberculosis, are hypo-inflammatory for a Th1-type immune response.[6,16–18]
Furthermore, the evolutionarily new strains appear to be disseminating more rapidly than their ancient counterparts. A similar distinction in mycobacterial virulence has been known of for some time at the species level; for example, the cell wall component lipomannan (LM) differs in its ability to induce TNF-α, depending on whether it is derived from M. tuberculosis or Mycobacterium smegmatis. If indeed there is a causative link between more virulent strains and the lack of a protective response by the host, some of the features that may facilitate this bear comparison with shared features in pathogenic fungi. In this article we shall consider some of the striking similarities between M. tuberculosis virulence factors and their fungal counterparts. In some of the examples provided it may be that other bacteria also share the related characteristic with fungi, particularly in species closely related to mycobacteria, but no other pathogenic species collectively demonstrates such a remarkable degree of similarity with fungi, of which all of those features enhance the virulence of the single most successful bacterial pathogen in human history.
Future Microbiol. 2014;9(5):657-668. © 2014 Future Medicine Ltd.