Cornelius Vanderbilt Professor of Biological Sciences Laurence J. Zwiebel is part of a team of researchers at Vanderbilt and the Johns Hopkins Malaria Research Institute who are working to understand how Plasmodium falciparium-the pathogen that causes malaria in humans-affects the mosquitoes that spread the disease. The research was spearheaded by Ann Carr, a current visiting scholar and former postdoctoral fellow in the Zwiebel Lab.
Through comparative analysis of mRNA between uninfected and infected mosquitoes old enough to transmit malaria, the researchers concluded that infected mosquitoes’ sense of smell was significantly enhanced, thus improving their ability to find hosts, Zwiebel said. This suggests that infection with the parasite provides the mosquito an advantage that promotes reproduction and disease transmission.
Beyond a more sensitive olfactory response, the researchers noted that the mRNA transcript profile of infected mosquitoes resembled that of much younger insects. “Infected mosquitoes revealed a physiology that had all the hallmarks of younger animals: more focused on reproduction, more robust immunologically and generally fitter than their uninfected middle-aged control siblings,” Zwiebel said. “This suggests there is broad generalized adaptive advantage to keeping malaria pathogens in the population. That, in part, explains the global persistence of malaria.”
The research team conducted their study within the challenging context of real-world infections that occur at very low levels. “We took enormous pains to conduct this study using very low intensity infections that align with the natural levels of infection seen in Africa,” Zwiebel said.
WHY IT MATTERS
Through taking the time and effort to replicate natural conditions to get these results, the researchers aim to demonstrate the feasibility and underscore the need to conduct malaria infection studies within natural parameters.
“This research should also provide a new understanding that while P. falciparium is a deadly parasitic pathogen to humans and other mammals, it is most definitely not a pathogen to the mosquitoes,” Zwiebel said. “In fact, our data strongly suggests there is a mutual symbiotic relationship between the Anopheles mosquito genus and P. falciparium.”
These data will inform future studies of Anopheles mosquitoes and P. falciparium and the global effort to reduce and eradicate human malaria. The Zwiebel Lab will begin unraveling the molecular and cellular mechanisms responsible for the increased olfactory sensitivity in malaria-carrying mosquitoes.
This work was conducted with the support of the Bloomberg Philanthropies, Vanderbilt University and National Institutes of Health grants NIAID AI122743 and NIAID AI127693.
The article, “Transcriptome Profiles of Anopheles gambiae Harboring Natural Low-Level Plasmodium Infection Reveal Adaptive Advantages for the Mosquito” was published in the journal Nature Scientific Reports on Nov. 19.
Researchers in the lab of George Dimopoulos, professor of molecular microbiology and immunology at Johns Hopkins, also contributed to this work.