The Complete Genome Sequence of the Emerging Pathogen Mycobacterium haemophilum Explains Its Unique Culture Requirements

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dc.contributor.authorTufariello, JoAnn M.en
dc.contributor.authorKerantzas, Christopher A.en
dc.contributor.authorVilcheze, Catherineen
dc.contributor.authorCalder, R. Brenten
dc.contributor.authorNordberg, Eric K.en
dc.contributor.authorFischer, Jack A.en
dc.contributor.authorHartman, Travis E.en
dc.contributor.authorYang, Evaen
dc.contributor.authorDriscoll, Timothyen
dc.contributor.authorCole, Laura E.en
dc.contributor.authorSebra, Roberten
dc.contributor.authorMaqbool, Shahina B.en
dc.contributor.authorWattam, Alice R.en
dc.contributor.authorJacobs, William R. Jr.en
dc.date.accessioned2019-05-10T14:53:57Zen
dc.date.available2019-05-10T14:53:57Zen
dc.date.issued2015-11en
dc.description.abstractMycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals. M. haemophilum exhibits a unique requirement for iron supplementation to support its growth in culture, but the basis for this property and how it may shape pathogenesis is unclear. Using a combination of Illumina, PacBio, and Sanger sequencing, the complete genome sequence of M. haemophilum was determined. Guided by this sequence, experiments were performed to define the basis for the unique growth requirements of M. haemophilum. We found that M. haemophilum, unlike many other mycobacteria, is unable to synthesize iron-binding siderophores known as mycobactins or to utilize ferri-mycobactins to support growth. These differences correlate with the absence of genes associated with mycobactin synthesis, secretion, and uptake. In agreement with the ability of heme to promote growth, we identified genes encoding heme uptake machinery. Consistent with its propensity to infect the skin, we show at the whole-genome level the genetic closeness of M. haemophilum with Mycobacterium leprae, an organism which cannot be cultivated in vitro, and we identify genes uniquely shared by these organisms. Finally, we identify means to express foreign genes in M. haemophilum. These data explain the unique culture requirements for this important pathogen, provide a foundation upon which the genome sequence can be exploited to improve diagnostics and therapeutics, and suggest use of M. haemophilum as a tool to elucidate functions of genes shared with M. leprae. IMPORTANCE Mycobacterium haemophilum is an emerging pathogen with an unknown natural reservoir that exhibits unique requirements for iron supplementation to grow in vitro. Understanding the basis for this iron requirement is important because it is fundamental to isolation of the organism from clinical samples and environmental sources. Defining the molecular basis for M. haemophilium's growth requirements will also shed new light on mycobacterial strategies to acquire iron and can be exploited to define how differences in such strategies influence pathogenesis. Here, through a combination of sequencing and experimental approaches, we explain the basis for the iron requirement. We further demonstrate the genetic closeness of M. haemophilum and Mycobacterium leprae, the causative agent of leprosy which cannot be cultured in vitro, and we demonstrate methods to genetically manipulate M. haemophilum. These findings pave the way for the use of M. haemophilum as a model to elucidate functions of genes shared with M. leprae.en
dc.description.notesThis work was supported by National Institutes of Health grants AI26170 and AI098925 to W.R.J.en
dc.description.sponsorshipNational Institutes of Health [AI26170, AI098925]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1128/mBio.01313-15en
dc.identifier.issn2150-7511en
dc.identifier.issue6en
dc.identifier.othere01313-15en
dc.identifier.urihttp://hdl.handle.net/10919/89481en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.titleThe Complete Genome Sequence of the Emerging Pathogen Mycobacterium haemophilum Explains Its Unique Culture Requirementsen
dc.title.serialmBioen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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