1887

Abstract

is the major aetiological agent of chronic pulmonary infections in patients with cystic fibrosis (CF). The metabolic pathways utilized by during these infections, which can persist for decades, are poorly understood. Several lines of evidence suggest that the glyoxylate pathway, which utilizes acetate or fatty acids to replenish intermediates of the tricarboxylic acid cycle, is an important metabolic pathway for adapted to the CF lung. Isocitrate lyase (ICL) is one of two major enzymes of the glyoxylate pathway. In a previous study, we determined that is dependent upon , which encodes ICL, to cause disease on alfalfa seedlings and in rat lungs. Expression of in PAO1, a isolate associated with acute infection, is regulated by carbon sources that utilize the glyoxyate pathway. In contrast, expression of in FRD1, a CF isolate, is constitutively upregulated. Moreover, this deregulation of occurs in other isolates associated with chronic infection, suggesting that high ICL activity facilitates adaptation of to the CF lung. Complementation of FRD1 with a PAO1 clone bank identified that negatively regulates . However, the deregulation of in FRD1 was not due to a knockout mutation of . Regulation of the glyoxylate pathway by RpoN is likely to be indirect, and represents a unique regulatory role for this sigma factor in bacterial metabolism.

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2010-04-01
2019-10-14
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