Can a Common Medical Practice Transform Candida Infections From Benign to Deadly?
Joan Stephenson, PhD SAN FRANCISCO—New research hints that a common medical practice—the use of heparin in intravascular catheters to discourage blockages by blood clots—may sometimes inadvertently trigger events that transform a benign fungal infection into a deadly illness. Themicrobe in question is Candida albicans, a yeast that often harmlessly colonizes patients. But C albicans has a darker side: it is also the leading cause of invasive fungal disease in premature infants and others with weakened immune systems, such as individuals infected with HIV, people recovering from surgery, and cancer or bone marrow transplantation patients. What transforms this microbial DrJekyll into a deadly Mr Hyde? Although many factors are likely to be involved, the new findings—though preliminary— suggest that heparin in intravascular catheters may play a role by triggering a series of events that result in a lifethreatening toxic shock–like reaction.
TERMS OF ATTACHMENT
natal ICUs, noted Hostetter. Even with antifungal therapy, the mortality rate in patients with systemic Calbicans infections approaches 30%. Although this yeast sometimes invades the bloodstream via a breach in the gut’s epithelial barrier, researchers
Candida albicans: What turns it deadly?
INT1, which encodes a C albicans surface protein, Int1p. Through a series of experiments, the investigators linked INT1 with adhesion, the ability to grow filaments, and virulence. Hostetter andcolleagues also have recently found evidence in laboratory and animal studies that Int1p may yet another function: enabling C albicans to replicate in the kidney and in urine. “Knockout” mutants lacking INT1 are unable to proliferate in urine—a hostile environment because of its high urea content—and they also have a somewhat impaired ability to grow and form normal filaments in mice. “Urea appears tobe a potent trigger for replication and filamentation, and Candida albicans expressing INT1 can survive in this milieu,” Hostetter said. If true, this may explain why uremic patients and patients undergoing peritoneal dialysis are susceptible to C albicans infections.
LOOKING FOR A TOXIN
Wadsworth Center, New York State Department of Health
The research, reported here at the 39th annualmeeting of the Infectious Diseases Society of America, is part of an ongoing effort by Margaret K. Hostetter, MD, of Yale University School of Medicine, and colleagues to understand how and why C albicans can turn deadly. During the past two decades, the incidence of candidemia in patients in intensive care units (ICUs) has soared from 1.5 to 60 infections per 10000 adult ICU admissions in adultsand from 23 to 123 infections per 10000 admissions to neo-
had long noted that in the majority of cases, patients who developed candidemia had central venous catheters in place for receiving infusions of antibiotics and other drugs, blood products, and other substances. Various Candida species on the skin of the patient or caregivers can insinuate their way into these catheters, adhere to theinside of the tubing, and form biofilms— complex layers of yeast cells that can be dislodged and disseminated through the bloodstream to virtually every organ of the body, Hostetter explained. In previous research on virulence factors that allow C albicans to attach to host cells and form invasive hyphae, Hostetter and colleagues identified a gene called
The investigators suspected, however, thatC albicans’ ability to stake out the kidneys was not sufficient to explain why the microbe can be so lethal. “After all, a substantial proportion of patients dying from candidemia have no renal lesions whatsoever,” said Hostetter. She and her colleagues turned their attention to searching for a toxin of some sort. Patients dying of candidemia have many of the same manifestations seen in patients...