Promising results for two genetic weapons against malaria
Johns Hopkins Bloomberg School of Public Health Oct 05, 2017
Two new papers by researchers at the Johns Hopkins Bloomberg School of Public HealthÂs Malaria Research Institute report successes for highly promising strategies against malaria, a disease that still kills more than 400,000 people each year, mostly children age five and under in sub-Saharan Africa.
The two studies discovered different ways by which resistance to the malaria parasite can spread into a mosquito population, potentially opening the way for the development of self-propagating malaria control strategies. The advantage of this feature is the lesser need to continuously apply malaria control measures such as insecticides and bed nets.
One team of researchers discovered a strain of bacteria that can spread rapidly and persist long-term among malaria-carrying mosquitoes. A genetically modified version of the bacterial strain strongly suppresses development of the malaria parasite, making the mosquitoes much less likely to transmit these parasites to humans.
A second research team discovered that a genetic modification that boosted the immune system of malaria-carrying mosquitoes not only suppresses malaria parasites in the insects but also can spread quickly in a test population, by changing the mosquitoes mating preferences.
Malaria is spread by female Anopheles mosquitoes carrying the malaria parasite. One promising way to prevent malaria, in addition to traditional approaches such as bed nets and insecticide, is to modify the mosquitoes so they are no longer capable of spreading the parasite to humans.
These new findings could lead to developing bacteria and mosquitoes that would be released into mosquito populations in the wild, and would propagate on their own to reduce malaria transmission to humans in endemic areas. These strategies are designed to be complementary and would be used in conjunction with things like bed nets and insecticides to diminish the transmission of disease.
The two papers appeared in the September 29 issue of the journal Science.
The discovery of the new mosquito-infecting bacterial strain was a chance event. ÂWe were working with a different bacterium when a researcher on the project happened to find evidence of a bacterial colony in our mosquitoes ovaries, said senior author Marcelo Jacobs-Lorena, a professor in the Bloomberg SchoolÂs Department of Molecular Microbiology and Immunology and a member of its Malaria Research Institute (JHMRI). ÂThat was unusual - normally we find bacteria only in the mosquito gut.Â
His team soon characterized these odd microbes as a strain of Serratia bacteria, and dubbed them Serratia AS1.
Jacobs-Lorena and other researchers have been developing genetically engineered bacteria that can infect mosquito populations and kill the malaria parasites the mosquitoes harbor, without harming the mosquitoes themselves. Getting such bacteria to spread efficiently has been a key challenge, but experiments revealed Serratia AS1 to be almost perfect for the task. Jacobs-Lorena and colleagues found that, unlike other mosquito-infecting bacteria, Serratia AS1 are easily transmitted from males to females during mating, and from female mosquitoes to their offspring. The bacteria also stably colonize the mosquito gut, where malaria parasites develop.
In one experiment, the scientists used Serratia AS1-laden sugar bait to infect males and virgin females representing just five percent of a mosquito test population, and found that in the next generation the bacterial strain was present in 100 percent of the larvae and adult mosquitoes. The researchers followed this mosquito population for two more generations - about a monthÂs timeÂand found that the bacteria remained ubiquitous. The results suggest that Serratia AS1 bacteria are likely to spread and persist long-term in wild mosquito populations.
The scientists modified Serratia AS1 by adding genes for five potent antimalarial
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The two studies discovered different ways by which resistance to the malaria parasite can spread into a mosquito population, potentially opening the way for the development of self-propagating malaria control strategies. The advantage of this feature is the lesser need to continuously apply malaria control measures such as insecticides and bed nets.
One team of researchers discovered a strain of bacteria that can spread rapidly and persist long-term among malaria-carrying mosquitoes. A genetically modified version of the bacterial strain strongly suppresses development of the malaria parasite, making the mosquitoes much less likely to transmit these parasites to humans.
A second research team discovered that a genetic modification that boosted the immune system of malaria-carrying mosquitoes not only suppresses malaria parasites in the insects but also can spread quickly in a test population, by changing the mosquitoes mating preferences.
Malaria is spread by female Anopheles mosquitoes carrying the malaria parasite. One promising way to prevent malaria, in addition to traditional approaches such as bed nets and insecticide, is to modify the mosquitoes so they are no longer capable of spreading the parasite to humans.
These new findings could lead to developing bacteria and mosquitoes that would be released into mosquito populations in the wild, and would propagate on their own to reduce malaria transmission to humans in endemic areas. These strategies are designed to be complementary and would be used in conjunction with things like bed nets and insecticides to diminish the transmission of disease.
The two papers appeared in the September 29 issue of the journal Science.
The discovery of the new mosquito-infecting bacterial strain was a chance event. ÂWe were working with a different bacterium when a researcher on the project happened to find evidence of a bacterial colony in our mosquitoes ovaries, said senior author Marcelo Jacobs-Lorena, a professor in the Bloomberg SchoolÂs Department of Molecular Microbiology and Immunology and a member of its Malaria Research Institute (JHMRI). ÂThat was unusual - normally we find bacteria only in the mosquito gut.Â
His team soon characterized these odd microbes as a strain of Serratia bacteria, and dubbed them Serratia AS1.
Jacobs-Lorena and other researchers have been developing genetically engineered bacteria that can infect mosquito populations and kill the malaria parasites the mosquitoes harbor, without harming the mosquitoes themselves. Getting such bacteria to spread efficiently has been a key challenge, but experiments revealed Serratia AS1 to be almost perfect for the task. Jacobs-Lorena and colleagues found that, unlike other mosquito-infecting bacteria, Serratia AS1 are easily transmitted from males to females during mating, and from female mosquitoes to their offspring. The bacteria also stably colonize the mosquito gut, where malaria parasites develop.
In one experiment, the scientists used Serratia AS1-laden sugar bait to infect males and virgin females representing just five percent of a mosquito test population, and found that in the next generation the bacterial strain was present in 100 percent of the larvae and adult mosquitoes. The researchers followed this mosquito population for two more generations - about a monthÂs timeÂand found that the bacteria remained ubiquitous. The results suggest that Serratia AS1 bacteria are likely to spread and persist long-term in wild mosquito populations.
The scientists modified Serratia AS1 by adding genes for five potent antimalarial
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