Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes. (11th February 2020)

• Record Type: Journal Article
• Authors: Knobloch, Paulina; Koliwer‐Brandl, Hendrik; Arnold, Fabian M.; Hanna, Nabil; Gonda, Imre; Adenau, Sophia; Personnic, Nicolas; Barisch, Caroline; Seeger, Markus A.; Soldati, Thierry; Hilbi, Hubert
• Is Part Of: Cellular microbiology. Volume 22:Number 5(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-11
• Subjects: ABC transporter -- Acanthamoeba -- amoeba -- bacterial pathogenesis -- carboxymycobactin -- Dictyostelium -- exochelin -- iron acquisition -- macrophage -- mycobactin -- pathogen vacuole -- siderophore -- tuberculosis; Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.13163
• Languages: English
• ISSNs: 1462-5814

Abstract

Abstract: Mycobacterium marinum is a model organism for pathogenic Mycobacterium species, including Mycobacterium tuberculosis, the causative agent of tuberculosis. These pathogens enter phagocytes and replicate within the Mycobacterium ‐containing vacuole, possibly followed by vacuole exit and growth in the host cell cytosol. Mycobacteria release siderophores called mycobactins to scavenge iron, an essential yet poorly soluble and available micronutrient. To investigate the role of M. marinum mycobactins, we purified by organic solvent extraction and identified by mass spectrometry the lipid‐bound mycobactin (MBT) and the water‐soluble variant carboxymycobactin (cMBT). Moreover, we generated by specialised phage transduction a defined M. marinum Δ mbtB deletion mutant predicted to be defective for mycobactin production. The M. marinum Δ mbtB mutant strain showed a severe growth defect in broth and phagocytes, which was partially complemented by supplying the mbtB gene on a plasmid. Furthermore, purified Fe‐MBT or Fe‐cMBT improved the growth of wild type as well as Δ mbtB mutant bacteria on minimal plates, but only Fe‐cMBT promoted the growth of wild‐type M. marinum during phagocyte infection. Finally, the intracellular growth of M. marinum Δ mbtB in Acanthamoeba castellanii amoebae was restored by coinfection with wild‐type bacteria. Our study identifies and characterises the M. marinum MBT and cMBT siderophores and reveals the requirement of mycobactins for extra‐ and intracellular growth of the pathogen. Abstract : Mycobacterium marinum, a pathogenic model organism for Mycobacterium tuberculosis, employs mycobactin siderophores for scavenging and uptake of the essential micro‐nutrient iron. In this study, the lipophilic mycobactin and hydrophilic carboxymycobactin compounds of M. marinum were purified by organic solvent extraction and identified by mass spectrometry. Moreover, an M. marinum Δ mbtB mutant strain generated by specialized phage transduction was defective for mycobactin biosynthesis and growth in broth and phagocytes, revealing the requirement for the mycobactins in extracellular and intracellular bacterial growth.