Naturally occurring a loss of a giant plasmid from Mycobacterium ulcerans subsp. shinshuense makes it non-pathogenic

Scientific Reports
Kazue NakanagaYoshihiko Hoshino

Abstract

Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a WHO-defined neglected tropical disease. All Japanese BU causative isolates have shown distinct differences from the prototype and are categorized as M. ulcerans subspecies shinshuense. During repeated sub-culture, we found that some M. shinshuense colonies were non-pigmented whereas others were pigmented. Whole genome sequence analysis revealed that non-pigmented colonies did not harbor a giant plasmid, which encodes elements needed for mycolactone toxin biosynthesis. Moreover, mycolactone was not detected in sterile filtrates of non-pigmented colonies. Mice inoculated with suspensions of pigmented colonies died within 5 weeks whereas those infected with suspensions of non-pigmented colonies had significantly prolonged survival (>8 weeks). This study suggests that mycolactone is a critical M. shinshuense virulence factor and that the lack of a mycolactone-producing giant plasmid makes the strain non-pathogenic. We made an avirulent mycolactone-deletion mutant strain directly from the virulent original.

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Citations

Oct 10, 2019·The American Journal of Tropical Medicine and Hygiene·Till F OmansenTimothy P Stinear
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Feb 24, 2021·Microbial Genomics·Sergio Mascarenhas Morgado, Ana Carolina Paulo Vicente

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Datasets Mentioned

BETA
AP017635

Methods Mentioned

BETA
electrophoresis
PCR

Software Mentioned

GATK
Integrative Genomics Viewer ( IGV )
R
Genome Analysis Toolkit ( GATK )
SAM
HaplotypeCaller
RealignerTargetCreator
GS Assembler

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