title: Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease.
abstract: BACKGROUND
  Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule with potent cytotoxic and immunomodulatory properties. These unique features make mycolactone an attractive biomarker for M. ulcerans disease. We sought to measure the concentration of mycolactone within lesions of patients with Buruli ulcer before, during and after antibiotic treatment to evaluate its association with the clinical and bacteriological response to therapy.
  
  
  METHODS
  Biopsies of M. ulcerans infected skin lesions were obtained from patients before, during and after antibiotic therapy. Lipids were extracted from the biopsies and concentration of mycolactone was assayed by mass spectrometry and a cytotoxicity assay and correlated with clinical and bacteriological response to therapy.
  
  
  RESULTS
  Baseline concentration of mycolactone measured by mass spectrometry predicted time to complete healing of small nodules and ulcers. Even though intra-lesional concentrations of mycolactone declined with antibiotic treatment, the toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks after the end of treatment for 8 weeks in a subgroup of patients with slowly healing lesions. Additionally viable bacilli were detected in a proportion of these slowly healing lesions during and after treatment.
  
  
  CONCLUSIONS
  Our findings indicate that baseline intra-lesional mycolactone concentration and its kinetics with antibiotic therapy are important prognostic determinants of clinical and bacteriological response to antibiotic treatment for Mycobacterium ulcerans disease. Mycolactone may be a useful biomarker with potential utility in optimising antibiotic therapy.
authors.affiliation: Komfo Anokye Teaching Hospital, Kumasi, Ghana. stephensarfo78@gmail.com.
authors.forename: Fred S
authors.initials: FS
authors.lastname: Sarfo
authors.forename: Richard O
authors.initials: RO
authors.lastname: Phillips
authors.forename: Jihui
authors.initials: J
authors.lastname: Zhang
authors.forename: Mohammed K
authors.initials: MK
authors.lastname: Abass
authors.forename: Justice
authors.initials: J
authors.lastname: Abotsi
authors.forename: Yaw A
authors.initials: YA
authors.lastname: Amoako
authors.forename: Yaw
authors.initials: Y
authors.lastname: Adu-Sarkodie
authors.forename: Clive
authors.initials: C
authors.lastname: Robinson
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wansbrough-Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D054312:Buruli Ulcer / Q000188:drug therapy* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D018942:Macrolides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008875:Middle Aged; D019911:Mycobacterium ulcerans / Q000302:isolation & purification*; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C117218:mycolactone
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