Insights into the evolutionary history of the virulent factor HBHA of Mycobacterium tuberculosis

MARIANA P. LANFRANCONI, ANA ARABOLAZA, HUGO GRAMAJO, HÉCTOR M. ALVAREZ

ARCHIVES OF MICROBIOLOGY

SPRINGER

Lugar: Berlin; Año: 2020

0302-8933

In Mycobacteriumtuberculosis, heparin-binding hemagglutinin (HBHAMT) has a relevant role in infection. It is also presentin non-virulent mycobacteria and ancient actinobacteria such as Rhodococcus opacus.To have a better understanding of the underlying mechanisms that shaped theevolutionary divergence of these proteins, we performed a comprehensivephylogenetic analysis of the regulatory sequences that drive the expression of hbhain saprophytic and pathogenic mycobacterial species. The alignment of the hbha loci showed the appearance of intergenicsequences containing regulatory elements upstream the hbha gene; this sequence arrangement ispresent only in slow-growing pathogenic mycobacteria. The heterologous expressionof HBHAMT inoleaginous R. opacus PD630 results in protein binding to lipid droplets,as it happens with HBHA proteins from saprophytic mycobacteria. We hypothesizethat mycobacterial hbha gene cluster underwent functional divergenceduring the evolutionary differentiation of slow-growing pathogenicmycobacteria. We propose here an evolutionary scenario to explain thestructural and functional divergence of HBHA in fast and slow-growingmycobacteria.