Coinfection With Influenza A Virus and Klebsiella oxytoca: An Underrecognized Impact on Host Resistance and Tolerance to Pulmonary Infections
The During the influenza season an average of 20% of the human population is infected, with this percentage varying from year to year depending on the virulence of the strains circulating that season. Secondary bacterial pneumonia following influenza A virus (IAV) infection is a serious complication whose prevalence and severity correlates with the virulence of the influenza strain. On average, 0.5% of previously healthy, young individuals and 2.5% of elderly or immunocompromised patients that contract IAV have bacterial coinfections; however, during times of influenza pandemic these numbers climb even higher and in the 1918 influenza virus pandemic up to 6.1% of all patients with IAV were thought to have secondary bacterial infections. In 1918, prior to the use of antibiotics, autopsies confirmed the presence of bacteria in up to 95% of fatalities. In the 2009 pandemic between 18 and 34% of IAV patients in the ICU had a bacterial coinfection and up to 55% of fatalities were associated with bacterial coinfection.
Pulmonary influenza A virus infection leads to suppression of the innate immune response to dermal injury
The innate immune response to lung infection takes priority at the expense of wound healing, according to a study published August 23 in the open-access journal PLOS Pathogens by a team of researcher at Brown University led by Amanda Jamieson. The innate immune system is responsible for responding to infections, clearing cancerous cells, healing wounds, and removing foreign substances. Although many of these functions happen simultaneously in life, most laboratory studies of the innate (or early) immune response focus on one activity. How the innate immune system responds to concurrent insults in different parts of the body is not well understood. To address this question, Dr. Meredith Crane, Dr. Amanda Jamieson and colleagues set out to determine the impact of a respiratory infection on wound healing.
Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia
Population heterogeneity is an important strategy that pathogens can utilize to escape antimicrobial treatment. This is now evidenced by our work in Candida albicans, a prevalent fungal pathogen that can occupy diverse niches in the human body, either as a commensal or as an invasive pathogen. Antifungal resistance has been described for all drugs used to treat infections by this species. Frontline therapies include azoles, a class of drugs which target the fungal cell membrane and inhibit cell growth. We now show that population heterogeneity of infecting isolates can enable azole escape – in many strains a subpopulation of C. albicans cells can still grow, albeit slowly, in the presence of high drug concentrations.
Surviving Deadly Lung Infections: Innate Host Tolerance Mechanisms in the Pulmonary System
Much research on infectious diseases focuses on clearing the pathogen through the use of antimicrobial drugs, the immune response, or a combination of both. Another way to survive an infection is to tolerate the alterations to homeostasis that occur during a disease state through a process called host tolerance or resilience, which is independent from pathogen burden. Alterations in homeostasis during infection are numerous and include tissue damage, increased inflammation, metabolic changes, temperature changes, and changes in respiration. By understanding tolerance mechanisms in the lung we can better address treatment options for deadly pulmonary infections.
Congratulations to Jenna Wurster who has received an NSF Fellowship Award for her work in the Belenky Lab!
Congratulations to Benjamin Korry who has received an NSF Fellowship Award for his work in the Belenky Lab!
Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor
Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. However, severe C. albicans infections are relatively rare, occurring mostly in the very young, the very old, and immunocompromised individuals. The fact that these infections are rare is interesting because as much as 80 percent of the population is asymptomatically colonized with C. albicans. It is thought that members of the human microbiota and the immune system work in concert to reduce C. albicans overgrowth through competition and modification of the growth environment. Here, we report that Escherichia coli (strain MG1655) outcompetes and kills C. albicans (strain SC5314) in vitro. We find that E. coli produces a soluble factor that kills C. albicans in a magnesium-dependent fashion such that depletion of available magnesium is essential for toxicity.
A central theme in biology is to understand how different signaling outputs can be accomplished by changes to signal transduction pathways. Here, we examined epigenetic differences between two cell states in the human fungal pathogen Candida albicans. We show that cells in the “white” state are sterile due to multiple bottlenecks in MAPK signaling relative to mating-competent “opaque” cells. Alleviation of these bottlenecks by reverse engineering effectively converts sterile white cells into sexually competent cells. These results have broad implications for understanding how epigenetic changes can impact MAPK expression and signaling output, including events associated with tumorigenesis. We also propose a model for how the white-opaque switch gained control of sexual reproduction in Candida during evolution.