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NMSU researchers fight mosquito-borne diseases with manipulation of mosquito gut bacteria

Bacteria inside a mosquito's gut may hold the key to control deadly diseases such as malaria, Dengue Fever and West Nile virus, which kill millions of people every year. Researchers at New Mexico State University are studying the mosquito gut bacteria in order to discover how mosquitos use their own gut bacteria to fight against malaria. They also want to try to reduce the mosquito population by disturbing gut bacteria to make mosquito lay fewer eggs.

Jiannong Xu, an assistant professor in NMSU's College of Arts and Sciences, is working on two courses of action to effectively prevent and ultimately eliminate mosquito-transmitted diseases. (Photo by Tonya Suther)

"To kill the entire mosquito species, that's impossible," said Jiannong Xu, an assistant professor in the College of Arts and Sciences. "There are so many different species, yet only a few are disease transmitters. If we can do something to control the mosquito population, then the public will be protected."

Xu, who has studied the interactions of mosquitos and malaria for 25 years, is exploring novel measures for mosquito control.

"Metagenomics is a new hot research approach that studies all kinds of different genomes present in an ecosystem." Xu said. "It helps us a lot, because now we can look at the complexities inside the mosquito gut. The bacteria in the mosquito gut help the mosquito to keep a relatively-high immune level, which means the immune system will kill most of the malaria."

Xu also said that removing or disturbing the gut bacteria might result in the mosquito laying fewer eggs.

"The essential nutrients that the bacteria provide for the mosquito host is very important for the mosquito lifecycle," Xu said. "If we can change that bacterial community inside the mosquito gut, then we might make the mosquito produce fewer eggs and the whole population will be smaller and it would help us to reduce malaria transmission."

Xu's research team includes a post-doctoral student, four graduate students and a research assistant. Together, they have engineered a gut bacterium that was tagged with a visible marker, florescent green protein, to track the dynamics of the microbial community.

Working with Xu are Ying Wang, a post-doctoral student, who is studying taxonomic classification of microbial community in the mosquito gut; Phanidhar Kukutla, a third year Ph.D. student studying mosquito gut microbial characterization and manipulation who was a recipient of the 2012 College of Arts and Sciences Outstanding Graduate Award and the travel award; Jijin Jiang, a second year Ph.D. student, tracking the dynamics of GFP tagged bacteria in the mosquito gut; Dong Pei, a first year Ph.D. student, working with engineering bacteria for paratransgenesis; Michael Best, a second year graduate student, annotating bacterial genomes; and Ivy Yu, a senior research assistant, working with bacterial tagging and engineering.

Xu, who received his doctorate at the Second Military Medical University in Shanghai, China, first became interested in the vector-borne diseases while doing parasitology work during post-doctoral studies at New York University.

He noted that parasitic diseases are a major problem in poorer countries, and he came to the U.S. because of the research opportunities.

In 2011, the Xu lab published a paper titled, "Dynamic gut microbiome across life history of the malaria mosquito Anopheles gambiae in Kenya." The paper was recognized and recommended by Faulty of 1000 (F1000Prime) and evaluated by George Dimopoulos, a professor at the Johns Hopkins Malaria Institute and member of Faulty of 1000.

The study shows that a dynamic bacterial community exists in the mosquito gut. There are common "core" bacterial inhabitants. Recently, the Xu lab also developed a protocol to do mosquito metagenomic RNAseq, which is coming out soon at JoVE, a peer reviewed, PubMed-indexed video journal. Using this method, they were able to characterize taxonomic and functional composition of the gut microbiome. They are working on the manuscript that will publish the findings to share the information with other scientists.

With support from the National Institute of Health, Xu and NMSU researchers are currently collaborating with Guiyang Yan, a professor at the University of California, Irvine, and Ingrid Faye, professor at Stockholm University in Switzerland.

"We isolated the bacterium Elizabethkigia here, while they isolated it in Europe," Xu said. "So then we compared the bacteria genomes and they were identical, which means this bacterium is very common with the malaria transmitters."

He hopes that the collaboration will produce an engineered bacterium that produces a toxin against mosquitoes.

"This is a worldwide problem," Xu said. "The richer countries, like the U.S and Europe, are responsible for helping local people fight this serious problem."

Xu has integrated his research into his teaching effectively. The research led Xu to the U.S. Department of Energy Joint Genome Institute where he served as a faculty cohort last year for the "Undergraduate Research in Microbial Genome Analysis" program. The mission of the DOE JGI is to advance genomics in support of the DOE missions related to clean energy generation and environmental characterization and cleanup.

"I provided a bacterial genome to the Genomic Encyclopedia of Bacteria and Archaea genome database," Xu said. "We isolated and sequenced the genome of bacterium Elizabethkingia anophelis Ag1 from mosquito gut. The availability of genome in the GEBA database enables the genome annotation for our students as well as those from other universities involved in the program."

While there, Xu also integrated the JGI's IMG Annotation Collaboration Toolkit into his bioinformatics and bacterial genetics classes. The multi-platform toolkit aims to enhance teaching gene/genome annotation in new ways.