Regulation of differentiation to the infective stage of the protozoan parasite Leishmania major by tetrahydrobiopterin

M. L. Cunningham; R. G. Titus; S. J. Turco; S. M. Beverley

doi:10.1126/science.1057740

Regulation of differentiation to the infective stage of the protozoan parasite Leishmania major by tetrahydrobiopterin

M. L. Cunningham, R. G. Titus, S. J. Turco, S. M. Beverley

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111 Scopus citations

Abstract

A critical step in the infectious cycle of Leishmania is the differentiation of parasites within the sand fly vector to the highly infective metacyclic promastigote stage. Here, we establish tetrahydrobiopterin (H₄B) levels as an important factor controlling the extent of metacyclogenesis. H₄B levels decline substantially during normal development, and genetic or nutritional manipulations showed that low H₄B caused elevated metacyclogenesis. Mutants lacking pteridine reductase 1 (PTR1) had low levels of H₄B, remained infectious to mice, and induced larger cutaneous lesions (hypervirulence). Thus, the control of pteridine metabolism has relevance to the mechanism of Leishmania differentiation and the limitation of virulence during evolution.

Original language	English
Pages (from-to)	285-287
Number of pages	3
Journal	Science
Volume	292
Issue number	5515
DOIs	https://doi.org/10.1126/science.1057740
State	Published - Apr 13 2001

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abstract = "A critical step in the infectious cycle of Leishmania is the differentiation of parasites within the sand fly vector to the highly infective metacyclic promastigote stage. Here, we establish tetrahydrobiopterin (H4B) levels as an important factor controlling the extent of metacyclogenesis. H4B levels decline substantially during normal development, and genetic or nutritional manipulations showed that low H4B caused elevated metacyclogenesis. Mutants lacking pteridine reductase 1 (PTR1) had low levels of H4B, remained infectious to mice, and induced larger cutaneous lesions (hypervirulence). Thus, the control of pteridine metabolism has relevance to the mechanism of Leishmania differentiation and the limitation of virulence during evolution.",

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AU - Beverley, S. M.

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AB - A critical step in the infectious cycle of Leishmania is the differentiation of parasites within the sand fly vector to the highly infective metacyclic promastigote stage. Here, we establish tetrahydrobiopterin (H4B) levels as an important factor controlling the extent of metacyclogenesis. H4B levels decline substantially during normal development, and genetic or nutritional manipulations showed that low H4B caused elevated metacyclogenesis. Mutants lacking pteridine reductase 1 (PTR1) had low levels of H4B, remained infectious to mice, and induced larger cutaneous lesions (hypervirulence). Thus, the control of pteridine metabolism has relevance to the mechanism of Leishmania differentiation and the limitation of virulence during evolution.

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Regulation of differentiation to the infective stage of the protozoan parasite Leishmania major by tetrahydrobiopterin

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