Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts
AuthorsWeerdenburg, Eveline M.
Abd El Ghany, Moataz
Otto, Thomas D.
ter Veen, Kars
van Stempvoort, Gunny
van der Sar, Astrid M.
Langridge, Gemma C.
Thomson, Nicholas R.
KAUST DepartmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Computer Science Program
Biological and Environmental Sciences and Engineering (BESE) Division
Bioscience Core Lab
Pathogen Genomics Laboratory
Computational Bioscience Research Center (CBRC)
MetadataShow full item record
AbstractThe interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution of intracellular pathogens, allowing them to survive and replicate in phagocytic cells of vertebrate hosts. To test this hypothesis on a genome-wide level, we determined for the intracellular pathogen Mycobacterium marinum whether it uses conserved strategies to exploit host cells from both protozoan and vertebrate origin. Using transposon-directed insertion site sequencing (TraDIS), we determined differences in genetic requirements for survival and replication in phagocytic cells of organisms from different kingdoms. In line with the general hypothesis, we identified a number of general virulence mechanisms, including the type VII protein secretion system ESX-1, biosynthesis of polyketide lipids, and utilization of sterols. However, we were also able to show that M. marinum contains an even larger set of host-specific virulence determinants, including proteins involved in the modification of surface glycolipids and, surprisingly, the auxiliary proteins of the ESX-1 system. Several of these factors were in fact counterproductive in other hosts. Therefore, M. marinum contains different sets of virulence factors that are tailored for specific hosts. Our data imply that although amoebae could function as a training ground for intracellular pathogens, they do not fully prepare pathogens for crossing species barriers.
CitationGenome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts 2015, 83 (5):1778 Infection and Immunity
PublisherAmerican Society for Microbiology
JournalInfection and Immunity
PubMed Central IDPMC4399070
- Conserved mechanisms of Mycobacterium marinum pathogenesis within the environmental amoeba Acanthamoeba castellanii.
- Authors: Kennedy GM, Morisaki JH, Champion PA
- Issue date: 2012 Mar
- A novel ESX-1 locus reveals that surface-associated ESX-1 substrates mediate virulence in Mycobacterium marinum.
- Authors: Kennedy GM, Hooley GC, Champion MM, Mba Medie F, Champion PA
- Issue date: 2014 May
- Transposon mutagenesis of Mycobacterium marinum identifies a locus linking pigmentation and intracellular survival.
- Authors: Gao LY, Groger R, Cox JS, Beverley SM, Lawson EH, Brown EJ
- Issue date: 2003 Feb
- Homeostasis of N-α-terminal acetylation of EsxA correlates with virulence in Mycobacterium marinum.
- Authors: Mba Medie F, Champion MM, Williams EA, Champion PA
- Issue date: 2014 Nov
- A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT-6 secretion.
- Authors: Gao LY, Guo S, McLaughlin B, Morisaki H, Engel JN, Brown EJ
- Issue date: 2004 Sep