Potential new front opens against parasite

In Africa, the Middle East, Mexico, Asia, and South America, more than one billion people are at risk of contracting leishmaniasis, a disease spread through sandflies and caused by the parasite Leishmania major, which manifests most commonly as skin lesions but with the potential for more harmful internal damage. Leishmaniasis mainly affects people in tropical and subtropical areas with limited access to medicine. As yet, no vaccine or drug ensures protection from this disease and some forms of leishmaniasis can be fatal without proper treatment.

Prajwal Gurung, PhD, assistant professor in Internal Medicine, and a team of researchers have discovered that the Leishmania major parasite impedes signaling protein murine-CXCL1’s function by promoting degradation at the C-terminal end. A recent publication from the team in PLOS Neglected Tropical Diseases finds that Leishmania major uses metalloproteases to evade and degrade CXCL1 signaling proteins. Furthermore, Gurung designed synthetic peptides that could inhibit Leishmania major metalloproteases by using cleavage information from the C-terminal end of CXCL1.

“Our study identified an immune evasion strategy employed by Leishmania major to evade innate immune responses in mice,” Gurung said, “and further highlights that targeting these Leishmania major metalloproteases may be important in controlling infection within the [infected] population and transmittance of the disease.” For the endemic populations such as Africa and the Middle East, the destruction of Leishmania major metalloproteases by synthetic peptides offers a technique to help limit the spread of the disease.

Collaborators on this publication include Internal Medicine’s Mary E. Wilson, MD; Matthew Yorek; Barun Poudel, PhD; Lalita Mazgaeen; and Marhsall Pope, PhD.

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