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

Kazue Nakanaga, Yoshitoshi Ogura, Atsushi Toyoda, Mitsunori Yoshida, Hanako Fukano, Nagatoshi Fujiwara, Yuji Miyamoto, Noboru Nakata, Yuko Kazumi, Shinji Maeda, Tadasuke Ooka, Masamichi Goto, Kazunari Tanigawa, Satoshi Mitarai, Koichi Suzuki, Norihisa Ishii, Manabu Ato, Tetsuya Hayashi, Yoshihiko Hoshino

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13 Citations (Scopus)


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.

Original languageEnglish
Article number8218
JournalScientific reports
Issue number1
Publication statusPublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • General


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