News Release 

Penn Medicine scientists engineer bacteria-killing molecules from wasp venom


University of Pennsylvania School of Medicine

Research News




"New antibiotics are urgently needed to treat the ever-increasing number of drug-resistant infections, and venoms are an untapped source of novel potential drugs. We think that venom-derived molecules such as the ones we engineered in this study are going to be a valuable source of new antibiotics," said study senior author César de la Fuente, PhD, a Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering at Penn.

De la Fuente and his team started with a small protein, or "peptide," called mastoparan-L, a key ingredient in the venom of Vespula lewisii wasps. Mastoparan-L-containing venom is usually not dangerous to humans in the small doses delivered by wasp stings, but it is quite toxic. It destroys red blood cells, and triggers a type of allergic/inflammatory reaction that in susceptible individuals can lead to a fatal syndrome called anaphylaxis--in which blood pressure drops and breathing becomes difficult or impossible.




The potency of mast-MO in these tests also appeared to be comparable to existing antibiotics such as gentamicin and imipenem--for which alternatives are needed due to the spread of resistant bacterial strains.

De la Fuente and his colleagues found evidence in the study that mast-MO kills bacterial cells by making their outer membranes more porous--which can also improve the ability of co-administered antibiotics to penetrate the cells--and by summoning antimicrobial white blood cells. At the same time, mast-MO appears to damp down the kind of harmful immune-overreaction that can lead to severe disease in some bacterial infections.

The researchers created dozens of variants of mast-MO and found several that appeared to have significantly enhanced antimicrobial potency with no toxicity to human cells. They hope to develop one or more of these molecules into new antibiotics--and they expect to take a similar approach in future to turn other venom toxins into promising antibiotic candidates.

"The principles and approaches we used in this study can be applied more broadly to better understand the antimicrobial and immune-modulating properties of peptide molecules, and to harness that understanding to make valuable new treatments," de la Fuente said.


Other co-authors on the study are co-first authors Osmar Silva and Marcelo Torres; and Jicong Cao, Elaine Alves, Leticia Rodrigues, Jarbas Resende, Luciano Lião, William Porto, Isabel Fensterseifer, Timothy Lu, and Octavio Franco.

Funding was provided by Penn Medicine's Institute for Diabetes, Obesity, and Metabolism; the Penn Mental Health AIDS Research Center; and Fundação de Amparo à Pesquisa do Estado de Goiás.





