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Newly found sensing system enables certain bacteria to resist human immune defenses

June 08, 2007

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health, have discovered a survival mechanism in a common type of bacteria that can cause illness. The mechanism lets the bacteria protect itself by warding off attacks from antimicrobial peptides (AMPs), which are defense molecules sent by the body to kill bacteria.

Bacteria are divided into two types, gram-positive and gram-negative, with the primary difference being the nature of the bacterial cell wall. Little is known about how gram-positive bacteria-such as those that can lead to food poisoning, skin disorders and toxic shock-avoid being killed by AMPs. AMPs are made by virtually all groups of organisms, including amphibians, insects, several invertebrates and mammals, including humans.

"Gram-positive bacteria are major threats to human health, especially due to increasing problems with drug resistance, and these findings may help chart a path to designing new drugs to bolster our antimicrobial treatment options," notes NIAID Director Anthony S. Fauci, M.D.

Led by Michael Otto, Ph.D., of NIAID's Rocky Mountain Laboratories (RML), the scientists used the gram-positive bacterium Staphylococcus epidermidis to study its response to a specific human AMP, human beta defensin 3. S. epidermidis is one of several hard-to-treat infectious agents that can be transmitted to patients in hospitals via contaminated medical implants. Findings by Dr. Otto's research group are published in the May 29 issue of the Proceedings of the National Academy of Science. Other well-known types of gram-positive bacteria include agents that cause anthrax, strep throat, flesh-eating disease and various types of food poisoning.

In gram-negative bacteria-such as those that cause plague and salmonellosis-a sensory and gene regulation system named PhoP/PhoQ protects invading bacteria, and scientists believe if they develop a better understanding of this system they could develop new drugs that are more effective at protecting people from infection.

Likewise, now Dr. Otto and his research group are hoping for similar possibilities for gram-positive bacteria with their discovery of "aps," which stands for antimicrobial peptide sensor. Aps has three parts: apsS, the sensor region; apsR, the gene regulation region; and apsX, which has an unknown function that Dr. Otto's group is investigating. Studies show that all three components of aps must be present for the system to function and effectively protect bacteria from AMPs.

"We are aware that for gram-negative bacteria, PhoP/PhoQ has been called a premier target for antimicrobial drug discovery, but little corresponding work has been done with gram-positive bacteria," Dr. Otto says. "Our group is excited by what we have demonstrated-an efficient and unique way that gram-positive bacteria control resistance-and we are continuing our investigation of the aps sensing system being used for drug development."

NIH/National Institute of Allergy and Infectious Diseases