Researchers at the University of Illinois at Chicago have discovered a molecular regulator that allows salmonella bacteria to switch from actively causing disease to lurking in a chronic but asymptomatic state called a biofilm.
Their findings are published in the online journal, eLife.
Biofilms cling to surfaces in the body, such as the bronchial tubes or artificial joints, often without causing illness. But they can be a reservoir of bacteria that detach and cause disease or infect new hosts. The biofilms are resistant to host defenses and antibiotics because their tightly-packed structure exposes little surface area for drugs to reach. Many pathogenic bacteria are able to switch from an infectious to a dormant state as a strategy for survival inside their hosts.
Linda Kenney, professor of microbiology and immunology at the UIC College of Medicine and lead author of the study, had been studying how salmonella survive inside immune system cells called macrophages. These white blood cells patrol the body and engulf viruses and bacteria they encounter. They encase their prey in a bubble called a vacuole that protects them from the invader until it can be destroyed.
Macrophages digest their quarry when the acidity inside the vacuole drops in response to the captive. But the bacteria have evolved a unique defense, enabling them to survive inside the vacuole and use the macrophage as a Trojan horse to travel elsewhere in the body undetected by other immune cells.
Kenney knew that a type of salmonella that causes typhoid fever in humans, called Salmonella typhi, and its mouse counterpart, Salmonella typhimurium, were able to survive inside macrophage vacuoles. She noticed that these bacteria did two things: inside the vacuole, they formed a kind of syringe -- a long, hollow filament to inject the vacuole with a host of proteins that altered it. They also quickly assumed the same acidity of the vacuole.
"These two defenses, together, allow salmonella to survive and replicate in the harsh conditions of the vacuole," Kenney says.
Further experiments revealed that sensing and mirroring the acidity, or pH, of the vacuole is what triggers salmonella to form the syringe.
"The syringe-forming and pH-adjusting genes are signaled to turn on by the lower pH inside the vacuole," Kenney says. But these same salmonella, equipped to survive the hostile environment inside a macrophage vacuole, were also able to exist free in the body of the host -- as biofilms.
"I wanted to know how Salmonella 'decide' between these two very different lifestyles," Kenney says.
Studying S. typhimurium, Kenney discovered that the molecular switch is a bacterial molecule called SsrB. As the macrophage vacuole starts to acidify, SsrB is activated and it turns on the genes needed to form the syringe and adjust the pH. When salmonella lives outside the vacuole, where pH levels are neutral, SsrB instead turns on genes for sticky proteins in the membrane that help bacteria bind to one another to form biofilms.
Kenney said that many disease-causing salmonella evolved from harmless strains partly by acquiring new genes from other germs in a process called horizontal gene transfer.
"Salmonella acquired their pH-adjusting and syringe-forming genes in this way, as well as the switch that turns them on and off - SsrB," she says. "The default mode, or its ancestral program, dictates that it make biofilms, cause no illness, and survive long enough to infect new hosts when the opportunity arises. The new genes allow it to survive the host's main defense -- the acidifying macrophage vacuole."
Understanding how bacteria switch from the disease-causing state to the biofilm state could help scientists develop anticancer drugs that encourage the formation of biofilms on tumors, Kenney says. "When salmonella forms biofilms on tumors, it releases TNF-alpha, a powerful anti-tumor molecule," she said. "If we can better control the formation of biofilms, we can target them to tumors for cancer therapy."
Co-authors on the study are Stuti Desai, Ricksen Winardhi, Michal Dykas and Yan Jie of the National University of Singapore and Saravanan Periasamy of the Nanyang Technological University.
This research was funded by grant 5IOBX-000372 from the U.S. Department of Veterans Affairs and a Research Center of Excellence grant to the Mechanobiology Institute at the National University of Singapore.
Source: University of Illinois at Chicago
CDC Urges Vigilance: New Recommendations for Monitoring and Testing H5N1 Exposures
July 11th 2025With avian influenza A(H5N1) infections surfacing in both animals and humans, the CDC has issued updated guidance calling for aggressive monitoring and targeted testing to contain the virus and protect public health.
IP LifeLine: Layoffs and the Evolving Job Market Landscape for Infection Preventionists
July 11th 2025Infection preventionists, once hailed as indispensable during the pandemic, now face a sobering reality: budget pressures, hiring freezes, and layoffs are reshaping the field, leaving many IPs worried about their future and questioning their value within health care organizations.
A Helping Hand: Innovative Approaches to Expanding Hand Hygiene Programs in Acute Care Settings
July 9th 2025Who knew candy, UV lights, and a college kid in scrubs could double hand hygiene adherence? A Pennsylvania hospital’s creative shake-up of its infection prevention program shows that sometimes it takes more than soap to get hands clean—and keep them that way.