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

Lanfranconi, Mariana P.; Arabolaza, Ana; Gramajo, Hugo; Alvarez, Héctor M.

doi:10.1007/s00203-021-02192-y

Cited by 4 publications

(2 citation statements)

References 39 publications

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“…In this work, r Rho HbhA was also found in LD induced when recombinant R. erythropolis was grown in nitrogen-limited conditions, confirming previous observations demonstrating that HbhA from M. tuberculosis was able to bind to LD of the recombinant M. bovis BCG strain and R. opacous PD63 [ 16 , 24 ]. The localization of this protein in LD had been associated with the assembling and maturation of those structures [ 14 , 16 ].…”

Section: Discussionsupporting

confidence: 90%

New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis

et al. 2021

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In recent years, knowledge of the role that protein methylation is playing on the physiopathogenesis of bacteria has grown. In Mycobacterium tuberculosis, methylation of the heparin binding hemagglutinin adhesin modulates the immune response, making this protein a subunit vaccine candidate. Through its C-terminal lysine-rich domain, this surface antigen interacts with heparan sulfate proteoglycans present in non-phagocytic cells, leading to extrapulmonary dissemination of the pathogen. In this study, the adhesin was expressed as a recombinant methylated protein in Rhodococcus erythropolis L88 and it was found associated to lipid droplets when bacteria were grown under nitrogen limitation. In order to delve into the role methylation could have in host–pathogen interactions, a comparative analysis was carried out between methylated and unmethylated protein produced in Escherichia coli. We found that methylation had an impact on lowering protein isoelectric point, but no differences between the proteins were found in their capacity to interact with heparin and A549 epithelial cells. An important finding was that HbhA is a Fatty Acid Binding Protein and differences in the conformational stability of the protein in complex with the fatty acid were observed between methylated and unmethylated protein. Together, these results suggest that the described role for this mycobacteria protein in lipid bodies formation could be related to its capacity to transport fatty acids. Obtained results also provide new clues about the role HbhA methylation could have in tuberculosis and point out the importance of having heterologous expression systems to obtain modified proteins.

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Section: Discussionsupporting

confidence: 90%

New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis

et al. 2021

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“…1A). In members of Mycobacterium genus, despite the mldsr ‐ mlds cluster is also conserved, both genes are separated by variable intergenic sequences containing regulatory elements upstream the hbha gene [14], suggesting a different regulation mechanism for this cluster in those bacteria (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

MLDSR, the transcriptional regulator of the major lipid droplets protein MLDS, is controlled by long‐chain fatty acids and contributes to the lipid‐accumulating phenotype in oleaginous Rhodococcus strains

Hernández,

Ledesma,

Moncalián

et al. 2024

The FEBS Journal

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Microorganism Lipid Droplet Small Regulator (MLDSR) is a transcriptional regulator of the major lipid droplets (LDs)‐associated protein MLDS in R. jostii RHA1 and R. opacus PD630. In this study, we investigated the role of MLDSR on lipid metabolism and triacylglycerol (TAG) accumulation in R. jostii RHA1 at physiological and molecular level. MLDSR gene deletion promoted a significant decrease of TAG accumulation, whereas inhibition of de novo fatty acid biosynthesis by the addition of cerulenin significantly repressed the expression of the mldsr‐mlds cluster under nitrogen‐limiting conditions. In vitro and in vivo approaches revealed that MLDSR‐DNA binding is inhibited by fatty acids and acyl‐CoA residues through changes in the oligomeric or conformational state of the protein. RNAseq analysis indicated that MLDSR not only controls the expression of its own gene cluster, but also of several genes involved in central, lipid‐ and redox metabolism, among others. We also identified putative MLDSR‐binding sites on the upstream regions of genes coding for lipid catabolic enzymes, and validated them by EMSA assays. Overexpression of mldsr gene under nitrogen‐rich conditions promoted an increase of TAG accumulation, and further cell lysis with TAG release to the culture medium. Our results suggested that MLDSR is a fatty acid‐responsive regulator that plays a dual role in cells by repression or activation of several metabolic genes in R. jostii RHA1. MLDSR seems to play an important role in the fine‐tuning regulation of TAG accumulation, LD formation, and cellular lipid homeostasis, contributing to the oleaginous phenotype of R. jostii RHA1 and R. opacus PD630.

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Intrabacterial lipid inclusions

Dargham

Mallick

Raze

et al. 2022

Biology of Mycobacterial Lipids

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

Cited by 4 publications

References 39 publications

New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis

New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis

MLDSR, the transcriptional regulator of the major lipid droplets protein MLDS, is controlled by long‐chain fatty acids and contributes to the lipid‐accumulating phenotype in oleaginous Rhodococcus strains

Intrabacterial lipid inclusions

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