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Chloramphenicol is a substrate for a novel nitroreductase pathway in Haemophilus influenzae

Arnold L Smith1, Alice L Erwin, Toni Kline

  • 1Microbial Pathogens Program, Seattle Biomedical Research Institute, Seattle, WA 98109-5219, USA. arnold.smith@sbri.org

Antimicrobial Agents and Chemotherapy
|May 29, 2007
PubMed

Insights

Chloramphenicol is metabolized by Haemophilus influenzae and Neisseria species into inactive compounds, a process not linked to antibiotic resistance. This nitroreductase pathway

Area of Science:

  • Microbiology
  • Biochemistry
  • Antibiotic Resistance

Background:

  • Chloramphenicol is a vital antibiotic for treating serious infections caused by Haemophilus influenzae and Neisseria meningitidis.
  • Its mechanism involves inhibiting bacterial protein synthesis.

Purpose of the Study:

  • To investigate the metabolic fate of chloramphenicol in H. influenzae and related bacteria.
  • To characterize the products of chloramphenicol metabolism and assess their impact on antibiotic resistance.

Main Methods:

  • Incubation of chloramphenicol with H. influenzae cells and lysates.
  • Analysis of metabolic products using biochemical techniques.
  • Testing chloramphenicol susceptibility in bacterial strains that metabolize the antibiotic.

Main Results:

  • Chloramphenicol is converted to a 4-aminophenyl allylic alcohol, which lacks antibacterial activity.
  • This alcohol can revert to the 1,3-diol or dehydrate to form an iminoquinone.
  • Metabolism occurs in Neisseria species and susceptible Haemophilus species, but not in E. coli or other tested bacteria.
  • The identified metabolic pathway does not confer chloramphenicol resistance.

Conclusions:

  • A novel nitroreductase pathway metabolizes chloramphenicol in H. influenzae and Neisseria species.
  • This pathway inactivates the antibiotic without mediating resistance.
  • Further research is needed to understand the physiological role of this pathway and the diversity of prokaryotic nitroreductase mechanisms.

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