Complete Genome Sequence of Mycobacterium ulcerans subsp.
            <i>shinshuense</i>

Yoshida, Mitsunori; Nakanaga, Kazue; Ogura, Yoshitoshi; Toyoda, Atsushi; Ooka, Tadasuke; Kazumi, Yuko; Mitarai, Satoshi; Ishii, Norihisa; Hayashi, Tetsuya; Hoshino, Yoshihiko

doi:10.1128/genomea.01050-16

Cited by 22 publications

(21 citation statements)

References 7 publications

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“…Scherr et al (22) showed that cydA is intact in the M. ulcerans subsp. shinshuense (a subspecies found in all or nearly all Japanese patients) genome (37) and that it is also functional. The gene is also intact in Mycobacterium marinum, thought to be the species from which all M. ulcerans evolved.…”

Section: Resultsmentioning

confidence: 99%

Shortening Buruli Ulcer Treatment with Combination Therapy Targeting the Respiratory Chain and Exploiting Mycobacterium ulcerans Gene Decay

Converse

Almeida

Tyagi

et al. 2019

Antimicrob Agents Chemother

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Buruli ulcer is treatable with antibiotics. An 8-week course of rifampin (RIF) and either streptomycin (STR) or clarithromycin (CLR) cures over 90% of patients. However, STR requires injections and may be toxic, and CLR shares an adverse drug-drug interaction with RIF and may be poorly tolerated. Studies in a mouse footpad infection model showed that increasing the dose of RIF or using the long-acting rifamycin rifapentine (RPT), in combination with clofazimine (CFZ), a relatively well-tolerated antibiotic, can shorten treatment to 4 weeks. CFZ is reduced by a component of the electron transport chain (ETC) to produce reactive oxygen species toxic to bacteria. Synergistic activity of CFZ with other ETC-targeting drugs, the ATP synthase inhibitor bedaquiline (BDQ) and the bc 1 :aa 3 oxidase inhibitor Q203 (now named telacebec), was recently described against Mycobacterium tuberculosis. Recognizing that M. tuberculosis mutants lacking the alternative bd oxidase are hypersusceptible to Q203 and that Mycobacterium ulcerans is a natural bd oxidasedeficient mutant, we tested the in vitro susceptibility of M. ulcerans to Q203 and evaluated the treatment-shortening potential of novel 3-and 4-drug regimens combining RPT, CFZ, Q203, and/or BDQ in a mouse footpad model. The MIC of Q203 was extremely low (0.000075 to 0.00015 g/ml). Footpad swelling decreased more rapidly in mice treated with Q203-containing regimens than in mice treated with RIF and STR (RIFϩSTR) and RPT and CFZ (RPTϩCFZ). Nearly all footpads were culture negative after only 2 weeks of treatment with regimens containing RPT, CFZ, and Q203. No relapse was detected after only 2 weeks of treatment in mice treated with any of the Q203-containing regimens. In contrast, 15% of mice receiving RIFϩSTR for 4 weeks relapsed. We conclude that it may be possible to cure patients with Buruli ulcer in 14 days or less using Q203-containing regimens rather than currently recommended 56-day regimens.

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Section: Resultsmentioning

confidence: 99%

Shortening Buruli Ulcer Treatment with Combination Therapy Targeting the Respiratory Chain and Exploiting Mycobacterium ulcerans Gene Decay

Converse

Almeida

Tyagi

et al. 2019

Antimicrob Agents Chemother

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“…The complete genome sequence of M. ulcerans subsp. shinshuense (ATCC 33728) was also reported by a Japanese group [13]. Comparison of the whole genome of M. ulcerans subsp.…”

Section: Genomementioning

confidence: 53%

“…shinshuense has a 5,899,681 bp chromosome with 65.64% GC content and a 166,617 bp giant plasmid with 62.76% GC content. The average nucleotide identities were 98.36% to M. ulcerans Agy99 and 99.10% to M. liflandii 128FXT [13]. The total number of coding DNA sequences (CDSs) in both M. ulcerans subsp.…”

Section: Genomementioning

confidence: 99%

“…The total number of coding DNA sequences (CDSs) in both M. ulcerans subsp. shinshuense and M. liflandii 128FXT were found to be roughly around 5000, approximately 800 CDSs more than in the M. ulcerans Agy99 chromosome (Table 1) [10][11][12][13]. With respect to insertion sequences (IS), IS2606 was much more abundant in M. ulcerans Agy99 than in M. ulcerans subsp.…”

Section: Genomementioning

confidence: 99%

“…With respect to insertion sequences (IS), IS2606 was much more abundant in M. ulcerans Agy99 than in M. ulcerans subsp. shinshuense and M. liflandii 128FXT (Table 1) [10][11][12][13].…”

Section: Genomementioning

confidence: 99%

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Buruli Ulcer in Japan

et al. 2019

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Epidemiology and Bacteriological and Genomic Features of M. ulcerans subsp. shinshuense 1.1 Epidemiology Japan is one of the few countries located in a temperate zone that reports cases of Buruli ulcer (BU). The first case, a 19-year-old female who presented with a chronic and necrotic ulcer on her left elbow, was reported by Mikoshiba et al. in 1982 [1]. This was considered to be an endemic infection due to the lack of a travel history outside the country. A taxonomic study using DNA hybridization assays was later performed on a mycobacterial strain (ATCC 33788) isolated from the skin ulcer lesion of this patient, revealing that this Japanese strain was highly similar to the classical Mycobacterium ulcerans strain ATCC 19423. However, the Japanese strain differed from the previously described M. ulcerans strain in mycolic acid

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