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Protozoans and Pathogens Make for an Infectious Mix

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Single-celled organisms in the environment are protecting pathogenic bacteria and priming them for human infection, an international team of researchers has discovered.

Microorganisms such as protozoa and bacteria have been conducting an “arms race” for billions of years. Now scientists investigating how the environment affects bacterial interactions with human hosts have discovered that for pathogenic bacteria, such as Vibrio cholerae, these interactions may have made them not only stronger but much more infectious.

The results provide a new understanding about the mechanisms of infection and disease transmission.

The new observation that strains of V. cholerae can be expelled into the environment after being ingested by protozoa, and that these bacteria are then primed for colonisation and infection in humans, could help explain why cholera is so persistent in aquatic environments. Parcels known as expelled food vacuoles (EFVs), which are encased in a membrane, protect the bacteria in the protozoan gut and after they are ejected into the environment.

The report, published in Nature Microbiology, is the result of an international study co-led by researchers from the ithree institute at the University of Technology Sydney (UTS), Singapore Centre for Environmental Life Sciences Engineering (SCELSE) at Nanyang Technological University, Singapore, University of New South Wales and Tufts University in the US.

Lead researcher Associate Professor Diane McDougald, from UTS and SCELSE, said the experimental evidence suggests protozoa may be a source of highly infectious pathogens in recreational waters, such as swimming pools and beaches, aquaculture and drinking water systems and cooling towers.

“Most opportunistic pathogens don’t transfer from person to person. Rather, infection is transferred via the environment,” Associate Professor McDougald said.

In the case of cholera, which is endemic in many countries, infection spreads via water.  Outbreaks occur when sanitation systems are inadequate or when damaged during natural disasters or war.

“Our results indicate that pathogenic Vibrios in EFVs are resistant to starvation and antibiotics, as well as the acidic conditions encountered in the human stomach,” Associate Professor McDougald said.

“Our hypothesis is that these bacteria have adaptive traits that have allowed them to either escape or survive being eaten by protozoan predators. These traits have evolved in the environment as a response to predation and not for the ability to cause disease in accidental hosts. Unfortunately, in humans, these adaptive traits can increase the ability of the bacteria to colonise the host and cause disease,” she said.

The researchers used a mouse model to demonstrate that not only were the pathogenic cells in EFVs fitter, they were also highly infectious, colonising mouse model intestines 10 times more efficiently than free-living cells.

Dr Gustavo Espinoza-Vergara, the lead author of the work and ithree institute Research Associate, said the findings show EFVs are, potentially, a threat to human health.

“More broadly, the results may apply to other opportunistic pathogens that are released by protozoa in EFVs, thus establishing a new way to investigate the transmission and impact of infectious diseases”.

There are currently no detection systems for EFVs that would allow for the monitoring of potential pathogenic outbreaks. The researchers say future research could identify biomarkers, for example, proteins on the surfaces of EFVs, so antibodies could be developed to enable real-time monitoring.

Professor McDougald said another solution would be to identify targets to prevent the production of EFVs is another solution.

“To do that we need to understand how and why the cells in EFVs are so much better at growth and colonisation than free living cells. It is important research because diseases like cholera often impact the world’s poorest people,” she said.

Professor Liz Harry, director of the ithree institute at UTS, commended the research team’s “superb science”.

“The discovery of this highly infectious form of cholera produced outside the human body provides an opportunity to detect it and reduce the incidence of cholera. This disease remains a global threat to public health, particularly in developing countries,” Professor Harry said.

Reference: Espinoza-Vergara, G., Noorian, P., Silva-Valenzuela, C. A., Raymond, B. B. A., Allen, C., Hoque, M. M., … McDougald, D. (2019). Vibrio cholerae residing in food vacuoles expelled by protozoa are more infectious in vivo. Nature Microbiology. https://doi.org/10.1038/s41564-019-0563-x 

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