Synergism in action: co-infection of a yeast and a bacterium
An article in the latest issue of Infection and Immunity caught my attention: “Candida albicans–Staphylococcus aureus Polymicrobial Peritonitis Modulates Host Innate Immunity” describes work by researchers at the Louisiana State University Health Science Center. Many models of infectious disease use virulence studies in animals such as mice. A typical experiment may infect an animal with a defined number of pathogenic organisms, and changes in health of the animal are measured–this is the basic premise of Koch’s Postulates, where the etiologic agent of a disease can be experimentally determined. Some diseases of humans may not be well mimicked in animal models, and this presents a problem when trying to study significant human diseases.
The work summarized here examined the disease produced by two separate pathogens, the Gram positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Infection of mice with either one of these pathogens was non lethal at the infectious doses used in their experiments. However, when an animal was co-infected with both the bacterium and the fungus at the same time and at the same individual dose, a 40% mortality rate was observed, with significant infiltration of the organisms into the peritoneum and other target organs. At the same time, a number of important immune system signalling hormones were also elevated in mice who were co-infected with both pathogens, leading to a much higher inflammatory response in those animals. Mice treated at the same time with the inflammation inhibitor indomethacin did not die. Further injection of mice with a second inflammatory medidator prostaglandin E2 at the same time as administering indomethacin overrode the protective effects of indomethacin, and significant mortality of mice was again observed. The authors conclude that combination of pathogens have very important effects on the innate immune response, and that the lethality of the disease is exacerbated by the powerful inflammatory response.
Nosocomial infections are a critical issue in US health care, with billions of dollars annually being adding to the total costs of our health care. The graphic to the left from our textbook illustrates the relative contributions of various classes of pathogens; the sections of the pie labeled “Gram-positive bacteria” and “Yeast” are comprised primarily of the two species in this report, S. aureus and C. albicans. Many of the organisms responsible for causing nosocomial infections do so due to the a perfect storm of conditions in health care–a population very susceptible individuals, healthy carriers moving between patients, use of antibiotics leading to resistance, medical procedures which can bypass normal routes of entry for these pathogens. The first inclination upon developing a nosocomial infection is to combat it with antibiotics, and in fact many surgical procedures may involve the prophylactic use of antibiotics to help avoid this outcome. But the use of antibiotics themselves can lead to problems in the form of rampant antibiotic resistance and loss of efficacy of those drugs. This research shows that an alternative approach that tweaks the host’s immune response might also be effective.