Researchers have found that Streptococcus pneumoniae, the bacteria that causes most pneumonia cases, secretes a toxin to help it move from one body to the next with the help of the host’s immune defenses.
The study, “Host-to-Host Transmission of Streptococcus pneumoniae Is Driven by Its Inflammatory Toxin, Pneumolysin,” was published in the journal Cell Host & Microbe.
The study explains a microbial strategy used by S. pneumoniae to spread to new hosts and why an organism expresses a toxin that damages the host upon which it depends.
S. pneumoniae resides asymptomatically in the nasopharynx of healthy carriers. The respiratory tract, sinuses, and nasal cavity are the parts of the body that are usually infected. But in susceptible individuals, such as the elderly, immunocompromised people, and children, the bacterium may become pathogenic, spreading to other locations and causing disease.
S. pneumoniae is the main cause of community-acquired pneumonia and meningitis in children and older people, and of septicemia in HIV-infected people. The methods of transmission include sneezing, coughing, and direct contact with an infected person.
Using mouse models of S. pneumoniae in their experiments, researchers from NYU Langone Medical Center found that the pathogen has evolved to produce a pore-forming cytotoxin called pneumolysin, which promotes mucosal inflammation, increasing nasal secretions and enabling cells lining mucous membranes to expel the bacteria from the body.
The researchers believe that these bacteria have evolved to gain a benefit from being expelled, riding the secretions out of the body and on to their next host. In their experiments, researchers observed that when S. pneumoniae was genetically altered to be unable to produce the toxin, it could not spread from one mouse to the next.
“Factors that allow for the host-to-host transmission of disease-causing bacteria have not been thoroughly investigated by the field as a means of prevention,” Jeffrey Weiser, MD, chair of the Department of Microbiology at NYU Langone, said in a news release. “Our findings provide evidence of the tool used by these bacteria to spread, which promises to guide the design of new kinds of countermeasures.”
According to the researchers, by secreting the pneumolysin toxin, S. pneumoniae is capable of both finding nutrients and leaving its current host to pass to the next one.
They believe the toxin induces a response from the body, drilling pores in cells to get nutrients. As a result, the toxin gets nutrients for the bacteria to hold them over while outside the body. Then, the researchers say, the secretions the toxin triggers ensure that they exit a body that is attacking them with inflammatory responses, helping them find a new host.
S. pneumoniae is known to spread more effectively when someone is sick, for example with the influenza virus. In previous studies conducted in mice, the secretions that accompany influenza viral infection were shown to help S. pneumoniae bacteria to overcome the population constraints that come with remaining in one host.
In the new study, the researchers genetically altered a mouse model of bacterial transmission to examine pneumococcal transmission in the absence of flu. They found that the inflammation caused by colonization of pneumococcal bacteria, especially in response to the pneumolysin toxin, caused the bacterial shedding necessary for transmission between hosts.
But why do bacteria that fully depend on their host trigger such a destructive toxin? According to the researchers, the benefit to the bacteria of a higher rate of transmission counterbalances the harmful effects of the toxin on the host.
“Our study results argue that toxins made by bacteria are central mediators of transmission between hosts, which makes them attractive as a potential ingredient in vaccines, to which they could be added specifically to block transmission,” Weiser concluded. “There are precedents in using disarmed bacterial toxins, or toxoids, as vaccine ingredients, as with existing vaccines against diphtheria, tetanus and pertussis.”
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