A. phagocytophilum is unusual in that it can delay apoptosis in human neutrophils, which presumably allows some of the bacteria to replicate and cause infection.
"This particular bacterium specifically seeks out neutrophils -- possibly the most lethal of all host defense cells -- and remarkably, can alter their function, multiply within them and thereby cause infection," says NIAID Director Anthony S. Fauci, M.D.
Dr. DeLeo says the findings contrast with what is known about other bacterial pathogens, most notably Staphylococcus aureus, which is of great interest because of its increasing resistance to antibiotic treatment. S. aureus, often simply referred to as "staph," are bacteria commonly found on the skin and in the noses of healthy people. Occasionally, staph can cause infection; most are minor, such as pimples, boils and other skin conditions. However, staph bacteria can also cause serious and sometimes fatal infections, such as bloodstream infections, surgical wound infections and pneumonia.
In their experiments, the research team compared the neutrophil response to A. phagocytophilum with that of a weak strain of S. aureus. Using microarray technology that allowed them to compare about 14,000 different human genes, the researchers discovered how the response to A. phagocytophilum deviates from that of S. aureus, and thus permits the HGA agent to survive.
"This study has given us a global model of how bacteria can inhibit neutrophil apoptosis," says Dr. DeLeo. "Our next step is to look at specific human genes or gene pathways within this model and try to determine which of these molecules help prolong cell life following infection." Information gathered from these and similar studies, he adds, could help researchers develop therapeutics to treat or
Source:NIH/National Institute of Allergy and Infectious Diseases