Using One Infection to Halt Another

Infections with the bacterium Clostridium difficile cause devastating colitis and recurrent symptoms of watery diarrhea, fever, nausea and loss of appetite.  Because they are often acquired in a hospital setting when a patient takes antibiotics, these are generally considered healthcare-associated infections (HAIs). While incidences of other HAIs are on the decline due to improvements in medical practice and precautions taken, C. difficile infection rates remain high.  One strategy used to treat these infections, called a fecal transplant, involves knocking out the perturbed and C. diffiicle-dominated gut bacterial communities of these patients and introducing a sample from a healthy gut bacterial community to replace the previous unstable community.  While effective, this treatment has run into some obstacles with regulation by the FDA.  The intact replacement communities used are taken from other, healthy individuals, but each person has a unique composition of microbial flora.  This heterogeneity in the transplants makes them hard for the FDA to regulate with universally-applicable support.

A paper published in PLOS Pathogens in July of this year explores an alternative approach to treating C. difficile infections, by using another infective agent:  a virus.  The virus this team, led by Rob Meijers, studied is a bacteriophage, meaning it infects bacterial cells rather than human ones.  Theoretically, this means introducing the virus would pose a threat only to the bacterial cells and not the human ones.  However, introducing the bacteriophage could still have important implications for the health of the patient.  The bacteriophages encode endolysins that degrade the cell walls of the C. difficile and thereby destroy the bacterial cell walls.  Perhaps the introduction of this virus could eliminate the bacterial infection and improve the health of the human host.

This scenario, in which the authors posit that introducing a second infectious agent might mitigate the negative health effects of the first infection present, is not typical.  In most cases, co-infection with two biological agents is thought to amplify the negative health effects caused by either of the two agents.  This phenomenon is called "syndemism" and is apparent, for example, in the "superinfection" of cells by one virus that are already infected by another virus, such as the infection of Hepatitis B-infected cells with Hepatitis D.  Another example is dengue virus, which is believed to cause the worst form of its disease---dengue hemorrhagic fever---when an individual is infected with two serotypes of dengue virus in succession.  Another well-known pairing involves not two viruses but one virus and one bacterium.  According to the World Health Organization, patients infected with HIV are 30 times more likely to develop a tuberculosis infection than individuals who are not infected with HIV!

---Laurie Rumker