Salmonella May Spread Further by Becoming Less Virulent
Researchers find that Salmonella Typhimurium has evolved a mechanism to inhibit its ability to cause disease and allow survival of its host in order to promote its own spread to new hosts.
A new study published online in the journal Cell has suggested that some bacteria may be able to prevent the anorexia response that occurs in an animal that they infect. This not only allows the infected animal to survive, but also helps the bacterium to spread to new hosts and continue to cause disease.
“It’s well known that infections cause a loss of appetite,” Janelle S. Ayres, PhD, from the Salk Institute for Biological Studies, La Jolla, California, told Contagion. According to Dr. Ayres and colleagues, this sickness-induced anorexia is a behavioral modification that is a kind of coping strategy used by the body to increase the animal’s chances of surviving the infection.
Dr. Ayres told Contagion that recent studies have focused on understanding how this loss of appetite functions in helping the host survive an infection. “Most of these studies have relied largely on injecting microbes or microbial projects into the circulation of the host, and asking how nutrient status affects the animal’s ability to survive the challenge,” she said. However, she stressed that the host is only part of the host-pathogen equation, and that one limitation of previous studies is that they have not examined how the host’s loss of appetite affects the pathogen’s behavior and its ability to cause disease.
“In the current study, we wanted to understand how the fasted state affects pathogen virulence in a natural host-pathogen system,” Dr. Ayres explained. Therefore, the researchers conducted a study in mice to examine the physiological role of sickness-induced anorexia in host defenses. They used Salmonella Typhimurium, a natural intestinal pathogen in mice and humans that easily transmits to new hosts. They also orally infected the mice with the bacterium, to mimic the natural route of transmission of this organism.
According to Dr. Ayres, hosts that were fasted when orally infected with Salmonella did worse than infected mice that were allowed to feed. However, this was not due to defects in the host immune response, because the levels of Salmonella in the intestines of fasted mice were similar to those in the fed mice that survived.
Instead, they found that the host’s feeding status affected pathogen behavior and virulence. In mice that were fasted, Salmonella became more virulent and invaded systemic tissues, including the liver and spleen, causing a typhoid-like disease. However, in mice that were fed, Salmonella did not spread to systemic tissues, caused less disease, and was shed in the feces of the mice. This suggests that “there are trade-offs between virulence and transmission,” said Dr. Ayres.
The researchers also discovered that Salmonella has evolved a gene and mechanism to block the sickness-induced anorexic response in its host. By inhibiting this response, the bacterium was less virulent in its host, did not spread to systemic tissues, and promoted survival of the host and its transmission to new hosts. The mechanism that Salmonella uses to inhibit sickness-induced anorexia involves manipulating the gut-brain circuitry that controls appetite. “Salmonella inhibits the inflammatory response in the intestine, preventing its signaling to the appetite control center in the brain via the vagus nerve, thereby preventing the induction of anorexia,” summarized Dr. Ayres.
Overall, the results of this study highlight how a bacterium typically known as a pathogen has evolved a mechanism to inhibit its ability to cause disease and allow survival of its host in order to promote its own spread to new hosts.
Dr. Ayres emphasized that these findings not only provide new appreciation for the role of nutrition in infection transmission, but also suggest there may simpler ways to treat infectious diseases—by using nutrition, for example. This is especially important now, given the rising problem of antibiotic resistance, she noted.
In future studies, Dr. Ayres added that she and her team would like to investigate whether microbial members of the human microbiome have evolved similar mechanisms to manipulate the gut-brain circuitry of their hosts to regulate appetite. They would also like to identify which specific nutrients regulate transmission of pathogens, and which ones inhibit invasion of pathogens. “If we can dissociate the two, we can develop new nutrient-based therapies to promote survival of infections and control of disease transmission,” she concluded.
Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.