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Infection and Immunity, November 2007, p. 5313-5324, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.01807-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In Vivo Evidence of Pseudomonas aeruginosa Nutrient Acquisition and Pathogenesis in the Lungs of Cystic Fibrosis Patients{triangledown} ,{dagger}

Mike S. Son,1 Wallace J. Matthews Jr.,2 Yun Kang,1 David T. Nguyen,1 and Tung T. Hoang1*

Department of Microbiology, College of Natural Sciences,1 Department of Pediatrics, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii2

Received 13 November 2006/ Returned for modification 23 February 2007/ Accepted 15 August 2007

One of the hallmarks of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients is very-high-cell-density (HCD) replication in the lung, allowing this bacterium to induce virulence controlled by the quorum-sensing systems. However, the nutrient sources sustaining HCD replication in this chronic infection are largely unknown. Here, we performed microarray studies of P. aeruginosa directly isolated from the lungs of CF patients to demonstrate its metabolic capability and virulence in vivo. In vivo microarray data, confirmed by real-time reverse transcription-PCR, indicated that the P. aeruginosa population expressed several genes for virulence, drug resistance, and utilization of multiple nutrient sources (lung surfactant lipids and amino acids) contributing to HCD replication. The most abundant lung surfactant lipid molecule, phosphatidylcholine (PC), induces key genes of P. aeruginosa pertinent to PC degradation in vitro as well as in vivo within the lungs of CF patients. The results support recent research indicating that P. aeruginosa exists in the lungs of CF patients as a diverse population with full virulence potential. The data also indicate that there is deregulation of several pathways, suggesting that there is in vivo evolution by deregulation of a large portion of the transcriptome during chronic infection in CF patients. To our knowledge, this is the first in vivo transcriptome analysis of P. aeruginosa in a natural infection in CF patients, and the results indicate several important aspects of P. aeruginosa pathogenesis, drug resistance, nutrient utilization, and general metabolism within the lungs of CF patients.

* Corresponding author. Mailing address: Department of Microbiology, College of Natural Sciences, University of Hawaii at Manoa, Honolulu, HI 96822. Phone: (808) 956-3522. Fax: (808) 956-5339. E-mail: tongh{at}hawaii.edu

{triangledown} Published ahead of print on 27 August 2007.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: V. J. DiRita

Infection and Immunity, November 2007, p. 5313-5324, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.01807-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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