Examination of widely used antimicrobial compound reveals new strategies to fight malaria

Dec 10, 2008

Scientists working on a common antimicrobial compound with antimalarial activity have discovered a range of new therapeutic strategies to combat malaria. The research, published by Cell Press in the December 11th issue of the journal Cell Host and Microbe, provides valuable insight into how the human malaria parasite's requirement for fatty acids can be exploited as it progresses through the distinct stages of its complex life cycle.

Infection with the human malaria parasite, Plasmodium falciparum, begins when an infected mosquito bites a human. Injected parasites migrate to the liver where they copy themselves inside liver cells and prepare to enter the bloodstream, invading red blood cells and initiating the blood stages that cause the clinical manifestations of the disease.

P. falciparum changes and proliferates rapidly during these life stages and requires an abundant source of fatty acid molecules to build new cell membranes. Blood stage parasites synthesize fatty acids using a type II fatty acid biosynthesis (FAS-II) pathway that is also employed by bacteria. FAS-II had been viewed as an excellent therapeutic target in parasites and bacteria as it is distinct from the type I (FAS-I) pathway used by mammals.

The FAS-II inhibitor triclosan has been widely used in antimicrobial creams, lotions and soaps and is often present as an additive in plastics, textiles and implantable medical devices. Earlier studies identified FabI, an enzyme in the FAS-II pathway, as the predicted target of triclosan in malaria parasites, propelling extensive research efforts to develop novel antimalarials based on this compound.

However, a new research study led by Dr. David A. Fidock from Columbia University showed that disruption of the FabI gene in P. falciparum or the rodent parasite P. berghei did not impede blood stage growth and that FabI was not the antimalarial target of triclosan. Fidock and colleagues also showed that triclosan was not as effective against the blood stage of the malaria parasite as was previously thought. "Although this enzyme has been extensively studied as a candidate drug target for blood stage malaria parasites, our data argue against the therapeutic potential of FabI, and indeed the entire FAS-II pathway, during infection of red blood cells," explains Dr. Fidock.

Nevertheless, Dr. Fidock and his colleagues went on to make an additional discovery. They demonstrated that an absence of FabI results in P. berghei parasites that, coming from the mosquito, are less infective and fail to complete the liver stage of development. These parasites are then typically unable to initiate the symptomatic blood stage infection. In contrast, during the blood stage, the parasites do not rely on FabI and appear to obtain fatty acids primarily by acquiring them from the host.

"We propose that therapeutic strategies to interfere with fatty acid processes in blood stage parasites should focus on scavenging these molecules taken from the host. This contrasts with liver stage parasites that depend on synthesizing their own fatty acids to meet their metabolic needs. Interference with FAS-II in liver stages now offers novel perspectives for prophylactic intervention," explains Dr. Fidock. "Our work also highlights the need for additional studies to elucidate how triclosan acts on blood stage parasites."

Source: Cell Press

Explore further: Zoologists tap into GPS to track badger movements

Related Stories

Nanotechnology against malaria parasites

Dec 09, 2014

Malaria parasites invade human red blood cells, they then disrupt them and infect others. Researchers at the University of Basel and the Swiss Tropical and Public Health Institute have now developed so-called ...

New oscillator for low-power implantable transcievers

Oct 24, 2014

Arash Moradi and Mohamad Sawan from Polytechnique Montreal in Canada discuss their new low-power VCO design for medical implants. This oscillator was implemented to provide the frequency deviation of frequency-shift-keying ...

Recommended for you

Zoologists tap into GPS to track badger movements

28 minutes ago

Zoologists from Trinity College Dublin's School of Natural Sciences are using GPS tracking technology to keep a 'Big Brother' eye on badgers in County Wicklow. By better understanding the badgers' movements and the reasons ...

Researchers clarify how DNA damage signaling works

1 hour ago

The DNA molecule is chemically unstable, giving rise to DNA lesions of various kinds. That is why DNA damage detection, signaling and repair, collectively known as the DNA damage response, are needed. The ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.