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dc.contributor.authorDragset, Marte Singsås
dc.contributor.authorIoerger, Thomas R.
dc.contributor.authorLoevenich, Maja
dc.contributor.authorHaug, Markus
dc.contributor.authorSivakumar, Niruja
dc.contributor.authorMarstad, Anne
dc.contributor.authorCardona, Pere-Joan
dc.contributor.authorKlinkenberg, Geir
dc.contributor.authorRubin, Eric J.
dc.contributor.authorSteigedal, Magnus
dc.contributor.authorFlo, Trude Helen
dc.description.abstractNontuberculous mycobacterial infections caused by the opportunistic pathogen Mycobacterium avium subsp. hominissuis (MAH) are currently receiving renewed attention due to increased incidence combined with difficult treatment. Insights into the disease-causing mechanisms of this species have been hampered by difficulties in genetic manipulation of the bacteria. Here, we identified and sequenced a highly transformable, virulent MAH clinical isolate susceptible to high-density transposon mutagenesis, facilitating global gene disruption and subsequent investigation of MAH gene function. By transposon insertion sequencing (TnSeq) of this strain, we defined the MAH genome-wide genetic requirement for virulence and in vitro growth and organized ∼3,500 identified transposon mutants for hypothesis-driven research. The majority (96%) of the genes we identified as essential for MAH in vitro had a mutual ortholog in the related and highly virulent Mycobacterium tuberculosis (Mtb). However, passaging our library through a mouse model of infection revealed a substantial number (54% of total hits) of novel virulence genes. More than 97% of the MAH virulence genes had a mutual ortholog in Mtb. Finally, we validated novel genes required for successful MAH infection: one encoding a probable major facilitator superfamily (MFS) transporter and another encoding a hypothetical protein located in the immediate vicinity of six other identified virulence genes. In summary, we provide new, fundamental insights into the underlying genetic requirement of MAH for growth and host infection.nb_NO
dc.publisherAmerican Society for Microbiologynb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleGlobal Assessment of Mycobacterium avium subsp. hominissuis Genetic Requirement for Growth and Virulencenb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.relation.projectNorges forskningsråd: 223255/F50nb_NO
dc.relation.projectNorges forskningsråd: 249901nb_NO
dc.description.localcodeCopyright © 2019 Dragset et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.nb_NO
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.unitnameMH fakultetsadministrasjon

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal