FEATURE ARTICLE
Pathogens, Host-Cell Invasion and Disease
Invading pathogens can co-opt even the cells of the immune system. New anti-infective drugs may arise from an understanding of this chemical warfare
Erich Gulbins, Florian Lang
New Weapons Against Disease
But apoptosis of the host cell may also be of benefit for the host, since pathogens released from the dying cell might then be taken up by macrophages that would destroy the pathogen. By sacrificing itself, the infected cell thus protects the body from a further progression of the infection. For instance, infection with Pseudomonas aeruginosa, an opportunistic bacterium that infects people with cystic fibrosis, triggers apoptosis of infected epithelial cells. Epithelial cells infected with Pseudomonas aeruginosa express two proteins on their surface: the CD95 receptor and the corresponding CD95 ligand. The ligand binds to the receptor and triggers apoptotic death of the infected cell. Indeed, mutant mice that are not able to express either the CD95 receptor or the ligand are killed by this pathogen, whereas mice that are able to express both proteins easily overcome a Pseudomonas aeruginosa infection. By analogy, the P2X7 receptor is assumed to play an important role in the killing of cells infected with Mycobacterium tuberculosis.
Bacteria are increasingly becoming resistant to various antibiotics. Multi-drug-resistant tuberculosis is growing into a serious health problem in Russia. For people with impaired immune systems, multi-resistant infectious bacteria have become a life-threatening problem. As the efficacy of existing drugs against many diseases declines, it is becoming increasingly important to find new ways to fight infectious organisms.
Moreover, there is yet no cure for most viral diseases. AIDS is devastating the population and economies of many African and Asian countries. At the same time, drug resistance is aiding the resurgence of malaria in Southeast Asia and Western Africa.
By understanding the nature of the infectious process, drug developers in academia and industry will gain the necessary knowledge to develop new treatments. These new approaches at fighting infections do not aim to kill the infecting pathogen as classical antibiotics do. If a pathogen can be prevented from entering and hiding in host cells, it will be visible to the immune system and thus killed by the body's own defense mechanisms. Pathogens are also less likely to evolve resistance to drugs that work this way. Treatments based on this concept include small molecules that block the surface structures that pathogens use to recognize and attach to target cells and block their ability to trigger internalization. The understanding of host-cell resistance can also open up new possibilities for treatment. A number of biotechnology companies have already developed anti-infectives and are testing their efficiency to prevent and cure bacterial infections in clinical trials.
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