Novel Chemotherapy Targeted at Candida glabrata

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Novel Chemotherapy Targeted at Candida glabrata

• Brenda Ormesher, MD
• Research Elective

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Research Goal

• Specifically wanted to look at minimum inhibitory
  activity of approximately 60 novel compounds and
  their activity against C. glabrata in a bench
  setting

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Candida glabrata

• Recently C. glabrata has become an important
  pathogen in immunocompromised hosts including
  patients undergoing chemotherapy and living with
  HIV
• Sites of infection include corneal, cardiac
  (endocarditis), vaginal, oral and disseminated
• Second most common form of disseminated
  candidiasis after C. albicans

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Candida glabrata

• Glabrata is known for its decreased sensitivity
  to azoles thought to be related to increased drug
  efflux
• MIC patterns of C. glabrata to common anti-fungal
  therapies (MIC mg/mL), making Amphotericin B the
  gold standard therapy for Glabrata infections

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Methods

• Wild type isolates of glabrata were obtained from
  stock cultures at Dr. Calderones lab
• Novel compounds were supplied by Bill Grouteas
  (Wichita State University)
• MIC testing was done by NCCLS guidelines with
  data points at 24 and 48hrs

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Sample Compounds
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Sample Compounds
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Research Hurdles

• Initially attempted to experiment with wild type
  strain BG14, however the strain would not grow in
  96 well plate and had to change to BG2
• Glabrata being a more resistant organism had a
  much broader and higher range of MIC than
  previously had been seen with C. albicans

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Results

• Appx 60 novel compounds were tested against wild
  type C. albicans and wild type C. glabrata
• Initial results show some action with appx 7 of
  the initial 60 compounds had activity against C.
  glabrata

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Preliminary Results
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Preliminary Results
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Preliminary Results

• Best activity
• Based on appx molecular weight of 300, MIC of 50
  mmol equates to 15 mg/mL

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Future

• Mechanism of therapy of novel compounds?
• Test other fungus against novel compounds to
  determine spectrum of activity?
• Potential for new antifungal therapy in the
  clinic?

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Thanks to Dr. Calderones Lab, including Neeraj
Deepu!Any Questions?