Reducing their natural signals: How sneaky germs hide from ants

Not only humans are social, ants are too. Group members are taking care of sick ones by providing collective hygiene measures. This presents germs with a task. They must circumvent the immunity of an individual ant and avoid the group's healthcare. A new study now published in Nature Ecology & Evolution reveals that germs develop a sneaky way to escape the ant colony's defense systems by reducing their detection cues.

Pathogens are disease-causing organisms. By natural selection, they develop evading mechanisms to outsmart the host's immune system and to get the upper hand. One way to support the immune system and fight back is medical intervention. However, this can lead to unwanted adaptions of pathogens as seen in antibiotic-resistant bacteria. Another strategy is social intervention. Some social groups like ants are trying to fight infection with "social immunity," the collective hygiene and health care measures to avoid spreading throughout the community. If and how pathogens can respond to this kind of group behavior, is still unknown.

The latest study by Professor Sylvia Cremer and her research team at the Institute of Science and Technology Austria (ISTA) shows the extraordinary effects of these kinds of host-parasite interactions. Together, with chemical ecologists at the University of Würzburg in Germany, the scientists took a close look at social ants, to see how pathogenic fungi respond to their hosts' social care intervention during infection. The results reveal that fungi reduce their chemical detection signals to outplay social immunity. The study is published today in Nature Ecology & Evolution.

More spores but less grooming

"Fungi infect the ants from the body surface and grow inside, but nestmates groom off many of the spores before they can even cause internal infection," explains Barbara Milutinović, one of the lead authors, former postdoc in the Cremer Group and now Marie Curie Sklodowska Fellow at Ruđer Bošković Institute in Croatia. The scientists set up an experiment where Argentine ants (Linepithemahumile) were infected with pathogenic Metarhizium fungi either in the absence or presence of caregiving colony members. "We found that the fungi fundamentally changed in response to the ant workers' caregiving," Milutinović continues. Over ten infection cycles, fungi which experienced grooming nestmate ants boosted their spore production compared to fungi accompanied by only individual ants. "Producing more spores will help the fungus counteract the spore-removal by helping nestmates. Yet, we were surprised to see that the ants showed less grooming against the spores," Sylvia Cremer adds. "This suggests, that the spores have become more difficult to detect by the ants."

Fungi lose their typical chemical profile

To check why ant workers had difficulties sensing fungi and to analyze possible fungal detection cues, the scientists teamed up with a chemical ecologist from the University of Würzburg. Local Professor Thomas Schmitt explains: "The fungi, that adapted to social hosts were perceived less strongly, due to a strong reduction of a fungi-specific compound called ergosterol." Ergosterol is an essential membrane compound, that all fungi have. By exposing the ants to pure fungal ergosterol or the slightly different non-fungal vertebrate equivalent, the researchers showed, that only the fungal compound induced intense grooming. Milutinović summarizes: "This demonstrates that fungal pathogens react to the presence of caregiving ants by reducing their characteristic fungal signals. They are no longer recognized as a disease threat and can escape the social immunity of the colony."

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Being clean and hygienic need not impair childhood immunity

The theory that modern society is too clean, leading to defective immune systems in children, should be swept under the rug, according to a new study by researchers at UCL and the London School of Hygiene & Tropical Medicine.

In medicine, the 'hygiene hypothesis' states that early childhood exposure to particular microorganisms protects against allergic diseases by contributing to the development of the immune system.

However, there is a pervading view (public narrative) that Western 21st century society is too hygienic, which means toddlers and children are likely to be less exposed to germs in early life and so become less resistant to allergies.

In this paper, published in the Journal of Allergy and Clinical Immunology, researchers point to four significant reasons which, they say, disprove this theory and conclude we are not "too clean for our own good."

Lead author, Emeritus Professor of Medical Microbiology Graham Rook (UCL Infection & Immunity), said: "Exposure to microorganisms in early life is essential for the 'education' of the immune and metabolic systems.

"Organisms that populate our guts, skin and airways also play an important role in maintaining our health right into old age: so throughout life we need exposure to these beneficial microorganisms, derived mostly from our mothers, other family members and the natural environment.

"But for more than 20 years there has been a public narrative that hand and domestic hygiene practices, that are essential for stopping exposure to disease-causing pathogens, are also blocking exposure to the beneficial organisms.

"In this paper, we set out to reconcile the apparent conflict between the need for cleaning and hygiene to keep us free of pathogens, and the need for microbial inputs to populate our guts and set up our immune and metabolic systems."

In a review of evidence, the researchers point to four factors.
 

• Firstly, the microorganisms found in a modern home are, to a significant degree, not the ones that we need for immunity.
• Secondly, vaccines, in addition to protecting us from the infection that they target, do a lot more to strengthen our immune systems, so we now know that we do not need to risk death by being exposed to the pathogens.
• Thirdly, we now have concrete evidence that the microorganisms of the natural green environment are particularly important for our health; domestic cleaning and hygiene have no bearing on our exposure to the natural environment.
• Finally, recent research demonstrates that when epidemiologists find an association between cleaning the home and health problems such as allergies, this is often not caused by the removal of organisms, but rather by exposure of the lungs to cleaning products that cause a type of damage that encourages the development of allergic responses.

Professor Rook added: "So cleaning the home is good, and personal cleanliness is good, but, as explained in some detail in the paper, to prevent spread of infection it needs to be targeted to hands and surfaces most often involved in infection transmission. By targeting our cleaning practices, we also limit direct exposure of children to cleaning agents.

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Towards better hand hygiene for flu prevention

Rubbing hands with ethanol-based sanitizers should provide a formidable defense against infection from flu viruses, which can thrive and spread in saliva and mucus. But findings published this week in mSphere challenge that notion -- and suggest that there's room for improvement in this approach to hand hygiene.

The influenza A virus (IAV) remains infectious in wet mucus from infected patients, even after being exposed to an ethanol-based disinfectant (EBD) for two full minutes, report researchers at Kyoto Profectural University of Medicine, in Japan. Fully deactivating the virus, they found, required nearly four minutes of exposure to the EBD.

The secret to the viral survival was the thick consistency of sputum, the researchers found. The substance's thick hydrogel structure kept the ethanol from reaching and deactivating the IAV.

"The physical properties of mucus protect the virus from inactivation," said physician and molecular gastroenterologist Ryohei Hirose, Ph.D, MD., who led the study with Takaaki Nakaya, PhD, an infectious disease researcher at the same school. "Until the mucus has completely dried, infectious IAV can remain on the hands and fingers, even after appropriate antiseptic hand rubbing."

The study suggests that a splash of hand sanitizer, quickly applied, isn't sufficient to stop IAV. Health care providers should be particularly cautious: If they don't adequately inactivate the virus between patients, they could enable its spread, Hirose said.

The researchers first studied the physical properties of mucus and found -- as they predicted -- that ethanol spreads more slowly through the viscous substance than it does through saline. Then, in a clinical component, they analyzed sputum that had been collected from IAV-infected patients and dabbed on human fingers. (The goal, said Hirose, was to simulate situations in which medical staff could transmit the virus.) After two minutes of exposure to EBD, the IAV virus remained active in the mucus on the fingertips. By four minutes, however, the virus had been deactivated.

Previous studies have suggested that ethanol-based disinfectants, or EBDs, are effective against IAV. The new work challenges those conclusions. Hirose suspects he knows why: Most studies on EBDs test the disinfectants on mucus that has already dried. When he and his colleagues repeated their experiments using fully dried mucus, they found that hand rubbing inactivated the virus within 30 seconds. In addition, the fingertip test used by Hirose and his colleagues may not exactly replicate the effects of hand rubbing, which through convection might be more effective at spreading the EBD.

For flu prevention, both the Centers for Disease Control and Prevention and the World Health Organization recommend hand hygiene practices that include using EBDs for 15-30 seconds. That's not enough rubbing to prevent IAV transmission, said Hirose.

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