SPECULATIONS ON THE INFLUENCE OF INFECTING PHENOTYPE ON VIRULENCE ANDANTIBIOTIC SUSCEPTIBILITY OF LEGIONELLA-PNEUMOPHILA

It is not clear how Legionella pneumophila, which is a ubiquitous aqua tic organism not possessing a mammalian reservoir, evolved the ability to cause human disease. The unusual ecology of the organism may play an important role in the transmission and virulence of legionella infe ctions. L. pneumophila can infect and kill specific species of free-li ving amoebae as well as multiplying as an intracellular parasite in hu man phagocytic cells. In nature L. pneumophila can survive and possibl y replicate in free suspension, and grow in biofilms and in protozoa t hus leading to diverse phenotypes, potentially with diverse virulence and susceptibility properties. Indeed, recent evidence shows that intr a-amoeba growth induces a phenotype that is dramatically different phy siologically to that obtained in vitro, with altered virulence and sus ceptibility properties. Growth in macrophages also has profound effect on the physiological properties of L. pneumophila. Many different str ess proteins are expressed by the organism as a result of intra-macrop hage growth. A heat shock protein is abundantly synthesised and may be presented on the surface of infected macrophages, which allows them t o be targeted by T-lymphocytes for destruction. The difficulties in su ccessfully treating Legionnaires' disease are probably influenced by t he intracellular location of L. pneumophila. Retrospective clinical st udies show that it is only drugs such as erythromycin, ciprofloxacin a nd rifampicin, which are capable of accumulating in phagocytic cells, that are efficacious in the treatment of legionnaires' disease. Despit e the use of such drugs treatment failures occur, but these do not app ear to be associated with the emergence of resistant strains. Studies have shown that although erythromycin and rifampicin can inhibit the m ultiplication of L. pneumophila in macrophages the organism is not kil led and can resume multiplying when the drugs are removed. Thus a comp etent cell mediated immune response is important in recovery from legi onella infections. There is an urgent need for greater understanding o f how the changes induced by intracellular growth affect sensitivity t o antibiotics and host defences. Immunocompromised patients, who have the highest mortality rates, are likely to gain the most from progress in the treatment of L. pneumophila infections.