Journal
INFECTION AND IMMUNITY
Volume 85, Issue 5, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00764-16
Keywords
Pseudomonas aeruginosa; sRNA; PrrF; PrrH; iron regulation; PQS; small RNA
Categories
Funding
- NIH grant [R01AI123320]
- University of Maryland School of Pharmacy
- University of Maryland Graduate Program in Life Sciences
- NIH-NIAID contract [HHSN272201000046C]
- University of Maryland School of Pharmacy Mass Spectrometry Center [SOP1841-IQB2014]
- University of Maryland Graduate School
- West Virginia University School of Medicine
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Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that requires iron for virulence. Iron homeostasis is maintained in part by the PrrF1 and PrrF2 small RNAs (sRNAs), which block the expression of iron-containing proteins under iron-depleted conditions. The PrrF sRNAs also promote the production of the Pseudomonas quinolone signal (PQS), a quorum sensing molecule that activates the expression of several virulence genes. The tandem arrangement of the prrF genes allows for expression of a third sRNA, PrrH, which is predicted to regulate gene expression through its unique sequence derived from the prrF1-prrF2 intergenic (IG) sequence (the PrrH(IG) sequence). Previous studies showed that the prrF locus is required for acute lung infection. However, the individual functions of the PrrF and PrrH sRNAs were not determined. Here, we describe a system for differentiating PrrF and PrrH functions by deleting the PrrH(IG) sequence [prrF(Delta H-IG)]. Our analyses of this construct indicate that the PrrF sRNAs, but not PrrH, are required for acute lung infection by P. aeruginosa. Moreover, we show that the virulence defect of the Delta prrF1-prrF2 mutant is due to decreased bacterial burden during acute lung infection. In vivo analysis of gene expression in lung homogenates shows that PrrF-mediated regulation of genes for iron-containing proteins is disrupted in the Delta prrF1-prrF2 mutant during infection, while the expression of genes that mediate PrrF-regulated PQS production are not affected by prrF deletion in vivo. Combined, these studies demonstrate that regulation of iron utilization plays a critical role in P. aeruginosa's ability to survive during infection.
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