ISSN:
1365-2958
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Biology
,
Medicine
Notes:
The development of new drugs for treating Pneumocystis carinii infections in AIDS patients is hampered by the lack of long-term culture systems, and by our generally limited knowledge of this organism. Recently, however, we observed significant activity of various benzimidazoles against growth of this organism in short-term cultures. Benzimidazoles inhibit microtubule polymerization; there is strong evidence that the primary target is the β-tubulin subunit. To understand the basis for benzimidazole activity against P. carinii, and to examine the apparent relatedness of this organism to fungi, we have cloned and sequenced the single β-tubulin gene from a rat P. carinii isolate. There was 89-91% identity at the amino acid level to β-tubulins from filamentous fungi, but only 79-82% identity to yeast and protozoal β-tubulins. Also, eight introns were distributed throughout the P. cariniiβ-tubulin gene in a pattern characteristic of filamentous fungi. Specific residues previously implicated in benzimidazole sensitivity were conserved in P. cariniiβ-tubulin. The polymerase chain reaction was used to amplify a segment of P. cariniiβ-tubulin DNA from bronchoalveolar lavages obtained from two patients with AIDS. There was considerable divergence at the DNA level between the human and rat sequences, but 100% identity at the ammo-acid level.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-2958.1992.tb02204.x
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