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Bacterial Research Points to New Mosquito-Borne Disease Strategy

— From bathroom in Panama to vector control candidate

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NEW ORLEANS -- With mosquitoes worldwide becoming increasingly resistant to standard insecticides, a hunt is on for novel approaches to vector control for diseases transmitted by the ubiquitous insects. That search took researchers at Johns Hopkins University in Baltimore to, among other places, a bathroom in Panama where they found a bacterial species that could jump-start those efforts.

In two presentations here at the American Society of Tropical Medicine and Hygiene (ASTMH) annual meeting, Hopkins researchers discussed their progress with Chromobacterium sp. Panama (Csp-P), components of which appear to be lethal both to mosquito larvae and to the adult insect.

In particular, results from a indicated that preparations of dead Csp-P were nearly 100% effective in killing larvae in field-type conditions.

And lab studies at Hopkins shed light on the mechanisms by which Csp-P kills mosquitoes. The prime initial suspect is a Csp-P biofilm peptide related to zeamine, an antibiotic known to be lethal to higher organisms including nematodes.

In introducing her talk on the lab research, PhD candidate Hannah MacLeod noted that resistance to pyrethrins, carbamates, organophosphates, and synthetic growth regulators has become common in mosquito populations around the world. This has forced public health authorities to change tactics frequently (confirmed in a separate ASTMH presentation on ), as well as prompting efforts to come up with new approaches, including so-called microbial pesticides. One already in use relies on Bacillus thuringiensis, but resistance to it, too, has emerged.

Hence the Hopkins effort to identify alternatives that turned up Csp-P, which the group first collected and isolated from that Panamanian bathroom, said Eric Caragata, PhD, MBA.

He told attendees that an inactive bacterial preparation is environmentally preferable to live bacteria, so the Hopkins team's first step was to devise a way to kill Csp-P without compromising its larvicidal/insecticidal properties. This turned out to be straightforward: air-drying with moderate heat was sufficient to inactivate the bacteria, and subsequent tests confirmed that they were still lethal to mosquito larvae from multiple clinically relevant species.

To make the strategy practical for mosquito control, the group pelletized the dead bacteria with other ingredients on which larvae would readily feed. These were then tested in two experiments: in a semi-enclosed research facility subject to normal temperature fluctuations but using lab-grown mosquito larvae, and then in a truly outdoor setting in which wild larvae were collected and placed in cups, along with the Csp-P pellets.

In both experiments, which included controls with placebo pellets, larvae exposed to the Csp-P preparations quickly died, while those in the control settings thrived.

As far as the specific mechanism by which Csp-P is lethal to mosquitoes, MacLeod explained that this research is still in its early stages. She reported on , one of which is also mosquitocidal and another, dubbed W10, that's not. Genome sequencing revealed that the W10 species lacked one gene that the other two carried, and that gene encodes the zeamine-like peptide.

Previous research suggested that , which raises the question of whether Csp-P could be harmful to beneficial insect species as well as mosquitoes. But Caragata told app that the Hopkins group tested the pellets on honeybees, cockroaches, certain caterpillars, and termites. He noted that "they have to eat it" in order for the preparation to have any effect, and in these studies the creatures weren't interested.

Primary Source

American Society of Tropical Medicine and Hygiene

Caragata E, et al “A novel insecticide developed from a non-live preparation of the bacterium Chromobacterium sp. Panama (Csp_P) effectively kills Aedes aegypti larvae” ASTMH 2018; Abstract LB-5397.

Secondary Source

American Society of Tropical Medicine and Hygiene

MacLeod H, et al “The role of biofilm formation in the mosquitocidal activity of Chromobacterium species Panama” ASTMH 2018; Abstract 1457.