Functional divergence of HBHA from Mycobacterium tuberculosis and its evolutionary relationship with TadA from Rhodococcus opacus.
Rhodococcus opacus PD630 and Rhodococcus jostii RHA1 are oleaginous bacteria able to synthesize and accumulate triacylglycerols (TAG) in lipid bodies (LB). Highly relevant to the structure of LB is a protein homologous to heparin-binding hemagglutinin (HBHA) (called TadA in rhodococci), which is a virulence factor found in Mycobacterium tuberculosis. HBHA is an adhesin involved in binding to non-phagocytic cells and extrapulmonary dissemination. We observed a conserved synteny of three genes encoding a transcriptional regulator (TR), the HBHA protein and a membrane protein (MP) between TAG-accumulating actinobacteria belonging to Rhodococcus, Mycobacterium, Nocardia and Dietzia genera, among others. A 354 bp-intergenic spacing containing a SigF-binding site was found between hbha and the TR genes in M. tuberculosis, which was absent in genomes of other investigated actinobacteria. Analyses of available "omic" information revealed that TadA and TR were co-induced in rhodococci under TAG-accumulating conditions; whereas in M. tuberculosis and Mycobacterium smegmatis, HBHA and TR were regulated independently under stress conditions occurring during infection. We also found differences in protein lengths, domain content and distribution between HBHA and TadA proteins from mycobacteria and rhodococci, which may explain their different roles in cells. Based on the combination of results obtained in model actinobacteria, we hypothesize that HBHA and TadA proteins originated from a common ancestor, but later suffered a process of functional divergence during evolution. Thus, rhodococcal TadA probably has maintained its original role; whereas HBHA may have evolved as a virulence factor in pathogenic mycobacteria.
Instituto de Biociencias de la Patagonia (INBIOP), Universidad Nacional de la Patagonia San Juan Bosco y CONICET, Km 4-Ciudad Universitaria 9000, Comodoro Rivadavia, Chubut, Argentina.
Mariana P
MP
Lanfranconi
Instituto de Biociencias de la Patagonia (INBIOP), Universidad Nacional de la Patagonia San Juan Bosco y CONICET, Km 4-Ciudad Universitaria 9000, Comodoro Rivadavia, Chubut, Argentina. Electronic address: halvarez@unpata.edu.ar.
Héctor M
HM
Alvarez
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D023281:Genomics; D037102:Lectins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D010802:Phylogeny; D026801:Synteny
D001426:Bacterial Proteins; D037102:Lectins; C104578:heparin-binding hemagglutinin
HBHA; Lipid bodies; Mycobacterium; Rhodococcus; TadA; Virulence factor