A recent Yale literature review published in the journal Cell Host & Microbe sheds light on the ways in which vector-borne parasites, like malaria or Lyme disease, use gut bacteria to more effectively infect and spread within their human hosts.
When bloodsucking insects pierce a host’s skin, they inject a salivary concoction replete with anti-clotting and vein-dilating agents that ensure that blood keeps flowing to the bite area. It is through this same saliva that many vector-borne infections are also transmitted.
According to the review’s author, Yale School of Medicine professor Serap Aksoy, researchers had previously found that when an infection is introduced by syringe, it is much less potent than when introduced by an insect. It was not until recently, however, that researchers at the National Institutes for Health discovered a possible mechanism at play — injected saliva contains not only anti-clotting and vein-dilating agents, but also host bacteria that can aid in parasitic infection.
“This opens up another target,” Aksoy said. “Typically we have been attacking the parasite itself, with anti-parasite genes in the insect — immune resistance — but now that we know that the bacteria may have a hand, we can focus our efforts on both.”
The bacteria that the researchers identified are native to the gut of the sandfly and can trigger release of the signal molecule interleukin-1β, which alerts the immune system to deploy fighters to the area. Neutrophils, a type of white blood cell, commonly respond to interleukins, and these neutrophils end up inadvertently protecting the parasite and ferrying it to distant parts of the body.
In the case of the sandfly, the bacteria in question originate in the gut. It makes sense, then, Aksoy said, that the parasite, Leishmania donavani, is gut-borne. This does not mean, however, that the study’s findings are relevant only to the few diseases spread by gut-borne vectors, she said. She added that there are also bacterial populations in the salivary glands, where many dangerous parasites like plasmodium, which causes malaria, and trypanosomiasis, which causes sleeping sickness, are harbored by vectors.
Removing these bacteria may significantly weaken a parasitic infection, which could prove successful in remedying diseases, Aksoy noted.
This tactic can even be applied to nonparasitic infections, like viruses, according to Martin Olivier, a researcher at McGill University who also studies sandfly gut bacteria.
“The viruses themselves may not be creating exosomes, we know that they cannot,” he said, referring to the cell structures the human body recognizes and to which it sends neutrophils. “But they may be modulating bacterial behavior to do so, and this might be part of the way viruses like Zika infect people so effectively.”
These exosomes can do even more to spread disease in humans. At times, viruses can even inject their own RNA into the exosomes, which can directly aid the virus’ spread throughout the body, Olivier noted.
Studying the effects of gut bacteria may hold promise for controlling vector-spread of disease in other ways. Yale researchers Connor Rosen and Noah Palm note that many organisms, both commensal and parasitic, in the gut of flying insects change the insects’ behavior to suit their own goals. For example, a bacteria in the gut of a biting insect might decrease the digestive functions of the insect, causing it to bite more people and further spread infection of the parasite.
According to Palm, sometimes a single microbe can affect entire host organisms. In studies of mice, for example, he noted that microbe populations could significantly decrease a mouse’s chance of succumbing to disease.
This new study adds to a decade-old body of research into the mechanics behind vector-borne disease transmission, Aksoy said.
“It seems like now, all the pieces are beginning to come together,” she said.
Vector-borne diseases account for more than a billion new infections and more than a million deaths each year, according to the World Health Organization.
Josh Purtell | firstname.lastname@example.org