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Fosmidomycin is an
antibioticAn antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
that was originally isolated from culture broths of bacteria of the genus
StreptomycesStreptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
. It specifically inhibits
DXP reductoisomeraseDXP reductoisomerase or is an enzyme that intraconverts 1-deoxy-D-xylulose 5-phosphate and 2-C-methyl-D-erythritol 4-phosphate.It is classified under ....
, a key enzyme in the
non-mevalonate pathwayThe non-mevalonate pathway or 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis is an alternative metabolic pathway leading to the formation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate that has been elucidated only...
of isoprenoid biosynthesis. It is a structural analogue of 2-C-methyl-D-erythrose 4-phosphate. It inhibits the
E. coli enzyme with a KI value of 38 nM (4),
MTBMTB may refer to:* Mike Thomas Brown, Professional Mixed Martial Artist & WEC Featherweight Champion* Matlock Bath railway station, England; National Rail station code MTB* Motor Torpedo Boat* Mountain bike or Mountain biking* Mycobacterium tuberculosis...
at 80 nM, and the
FrancisellaFrancisella is a genus of pathogenic, Gram-negative bacteria. They are small coccobacillary or rod-shaped, non-motile organisms, which are also facultative intracellular parasites of macrophages...
enzyme at 99 nM.
The discovery of the non-mevalonate pathway in malaria parasites has indicated the use of fosmidomycin and other such inhibitors as
antimalarialAntimalarial medications, also known as antimalarials, are designed to prevent or cure malaria. Such drugs may be used for some or all of the following:* Treatment of malaria in individuals with suspected or confirmed infection...
drugs. Indeed, fosmidomycin has been tested in combination treatment with
clindamycinClindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
for treatment of
malariaMalaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
with favorable results. It has been shown that an increase in copy number of the target enzyme (
DXP reductoisomeraseDXP reductoisomerase or is an enzyme that intraconverts 1-deoxy-D-xylulose 5-phosphate and 2-C-methyl-D-erythritol 4-phosphate.It is classified under ....
) correlates with
in vitroIn vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
fosmidomycin resistance in the lethal
malariaMalaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
parasite,
Plasmodium falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...
.