Scholars@Duke
Journal cover image

Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans.

Publication ,  Journal Article
Lodge, JK; Jackson-Machelski, E; Toffaletti, DL; Perfect, JR; Gordon, JI
Published in: Proc Natl Acad Sci U S A
December 6, 1994
Published version (DOI) Link to item

Cryptococcus neoformans is a major cause of systemic fungal infection in immunocompromised patients. Myristoyl-CoA:protein N-myristoyltransferase (Nmt) catalyzes the transfer of myristate (C14:0) from myristoyl-CoA to the N-terminal glycine of a subset of cellular proteins produced during vegetative growth of C. neoformans. A Gly487-->Asp mutation was introduced into C. neoformans NMT by targeted gene replacement. The resulting strains are temperature-sensitive myristic acid auxotrophs. They are killed at 37 degrees C when placed in medium lacking myristate and, in an immunosuppressed animal model of cryptococcal meningitis, are completely eliminated from the subarachnoid space within 12 days of initial infection. C. neoformans and human Nmts exhibit differences in their peptide substrate specificities. These differences can be exploited to develop a new class of fungicidal drugs.

Duke Scholars

Jennifer Lodge
Author Jennifer Lodge Molecular Genetics and Microbiology
Dena L. Toffaletti
Author Dena L. Toffaletti Medicine, Infectious Diseases
John Robert Perfect
Author John Robert Perfect Medicine, Infectious Diseases
Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.91.25.12008

ISSN

0027-8424

Publication Date

December 6, 1994

Volume

91

Issue

25

Start / End Page

12008 / 12012

Location

United States

Related Subject Headings

  • Temperature
  • Substrate Specificity
  • Subarachnoid Space
  • Restriction Mapping
  • Recombinant Proteins
  • Polymerase Chain Reaction
  • Point Mutation
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Meningitis, Cryptococcal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lodge, J. K., Jackson-Machelski, E., Toffaletti, D. L., Perfect, J. R., & Gordon, J. I. (1994). Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans. Proc Natl Acad Sci U S A, 91(25), 12008–12012. https://doi.org/10.1073/pnas.91.25.12008
Lodge, J. K., E. Jackson-Machelski, D. L. Toffaletti, J. R. Perfect, and J. I. Gordon. “Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans.” Proc Natl Acad Sci U S A 91, no. 25 (December 6, 1994): 12008–12. https://doi.org/10.1073/pnas.91.25.12008.
Lodge JK, Jackson-Machelski E, Toffaletti DL, Perfect JR, Gordon JI. Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12008–12.
Lodge, J. K., et al. “Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans.” Proc Natl Acad Sci U S A, vol. 91, no. 25, Dec. 1994, pp. 12008–12. Pubmed, doi:10.1073/pnas.91.25.12008.
Lodge JK, Jackson-Machelski E, Toffaletti DL, Perfect JR, Gordon JI. Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12008–12012.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.91.25.12008

ISSN

0027-8424

Publication Date

December 6, 1994

Volume

91

Issue

25

Start / End Page

12008 / 12012

Location

United States

Related Subject Headings

  • Temperature
  • Substrate Specificity
  • Subarachnoid Space
  • Restriction Mapping
  • Recombinant Proteins
  • Polymerase Chain Reaction
  • Point Mutation
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Meningitis, Cryptococcal