Pseudomonas aeruginosa is a malicious opportunistic pathogen both in terms of the severity and the outcome of infections it causes. A significant proportion of patients with cystic fibrosis (CF) are coloized at an early age (1-2 yrs.) and many ultimately succumb to a chronic lung infection from P. aeruginosa. The reason for the extraordinary pathogenicity of P. aeruginosa in these patients, as compared to that of other Pseudomonas spp. is not clear. The myriad of virulence factors, alone or in combination, to even the simplest of P. aeruginosa infections has not yet been elucidated. Expression of virtually all the identified major virulence determinants in this organism is regulated by a variety of environmental conditions which the organism encounters at some point in its journey through the infected host. For example, iron levels undoubtedly play a role in the pathogenesis of P. aeruginosa infections. Production of specific virulence factors of this organism are induced in response to limiting amounts of iron a natural occurring environment in mammalian hosts. Some of these factors are crucial to acquisition of iron from the host. On the other hand P. aeruginosa must also limit its intake of iron to avoid oxidative damage from the iron catalyzed production of hydroxyl radicals. It is not completely clear how this intricate balance is maintained. In P. aeruginosa endocarditis, O2 tension has a significant influence on the outcome of this disease. On the right side of the heart O2 tension is 40 mm Hg lower than is on the left side. This variance contributes to the milder outcome of right side disease as compared to the much poorer prognosis associated with left-sided disease. In contrast to iron concentration, much less is known about the effects of O2 on the pathogenic potential of P. aeruginosa. Consequently further studies on this regulatory mechanism are clearly warranted. Finally, because O2 tension and iron levels in a given environment (e.g. human host) are exquisitely interrelated, analyses of their effects require integrated approaches. A more comprehensive understanding of iron and O2 response genes in the expression of virulence by this opportunistic pathogen could aid in the rational development of effective measures for the prevention and therapy of P. aeruginosa infections.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Special Emphasis Panel (ZRG5-MBC-1 (01))
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Taylor, Christopher E,
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University of Colorado Denver
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