Intraspecies Signaling between Common Variants of Pseudomonas aeruginosa Increases Production of Quorum-Sensing-Controlled Virulence Factors

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa damages hosts through the production of diverse secreted products, many of which are regulated by quorum sensing (QS). The lasR gene, which encodes a central QS regulator, is frequently mutated in clinical isolates from chronic infections, and loss of LasR function (LasR−) generally impairs the activity of downstream QS regulators RhlR and PqsR. We found that in cocultures containing LasR+ and LasR− strains, LasR− strains hyperproduce the RhlR/RhlI-regulated antagonistic factors pyocyanin and rhamnolipids in diverse models and media and in different strain backgrounds. Diffusible QS autoinducers produced by the wild type were not required for this effect. Using transcriptomics, genetics, and biochemical approaches, we uncovered a reciprocal interaction between wild-type and lasR mutant pairs wherein the iron-scavenging siderophore pyochelin produced by the lasR mutant induced citrate release and cross-feeding from the wild type. Citrate, a metabolite often secreted in low iron environments, stimulated RhlR signaling and RhlI levels in LasR−but not in LasR+ strains. These studies reveal the potential for complex interactions between recently diverged, genetically distinct isolates within populations from single chronic infections. IMPORTANCE Coculture interactions between lasR loss-of-function and LasR+ Pseudomonas aeruginosa strains may explain the worse outcomes associated with the presence of LasR− strains. More broadly, this report illustrates how interactions within a genotypically diverse population, similar to those that frequently develop in natural settings, can promote unpredictably high virulence factor production.

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Intra-species signaling between Pseudomonas aeruginosa genotypes increases production of quorum sensing controlled virulence factors

10.1101/2020.04.29.068346 ◽

2020 ◽

Author(s):

Dallas L. Mould ◽

Nico J. Botelho ◽

Deborah A. Hogan

Keyword(s):

Pseudomonas Aeruginosa ◽

Transcription Factor ◽

Quorum Sensing ◽

Opportunistic Pathogen ◽

Diverse Population ◽

Loss Of Function ◽

Wild Type ◽

Natural Settings ◽

Citrate Release ◽

Virulence Factor Production

AbstractThe opportunistic pathogen Pseudomonas aeruginosa damages hosts through the production of diverse secreted products, many of which are regulated by quorum sensing. The lasR gene, which encodes a central quorum-sensing regulator, is frequently mutated, and loss of LasR function impairs the activity of downstream regulators RhlR and PqsR. We found that in diverse models, the presence of P. aeruginosa wild type causes LasR loss-of-function strains to hyperproduce RhlR/I-regulated antagonistic factors, and autoinducer production by the wild type is not required for this effect. We uncovered a reciprocal interaction between isogenic wild type and lasR mutant pairs wherein the iron-scavenging siderophore pyochelin, specifically produced by the lasR mutant, induces citrate release and cross-feeding from wild type. Citrate stimulates RhlR signaling and RhlI levels in LasR-but not in LasR+ strains, and the interactions occur in diverse media. Co-culture interactions between strains that differ by the function of a single transcription factor may explain worse outcomes associated with mixtures of LasR+ and LasR loss-of-function strains. More broadly, this report illustrates how interactions within a genotypically diverse population, similar to those that frequently develop in natural settings, can promote net virulence factor production.

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Pseudomonas aeruginosa las and rhl quorum-sensing systems are important for infection and inflammation in a rat prostatitis model

Microbiology ◽

10.1099/mic.0.028464-0 ◽

2009 ◽

Vol 155 (8) ◽

pp. 2612-2619 ◽

Cited By ~ 21

Author(s):

Lisa K. Nelson ◽

Genevieve H. D'Amours ◽

Kimberley M. Sproule-Willoughby ◽

Douglas W. Morck ◽

Howard Ceri

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Tissue Damage ◽

Inflammatory Markers ◽

Bacterial Colonization ◽

Opportunistic Pathogen ◽

Infection Model ◽

Chronic Infections ◽

Strain Pao1 ◽

Rat Prostate

Pseudomonas aeruginosa frequently acts as an opportunistic pathogen of mucosal surfaces; yet, despite causing aggressive prostatitis in some men, its role as a pathogen in the prostate has not been investigated. Consequently, we developed a Ps. aeruginosa infection model in the rat prostate by instilling wild-type (WT) Ps. aeruginosa strain PAO1 into the rat prostate. It was found that Ps. aeruginosa produced acute and chronic infections in this mucosal tissue as determined by bacterial colonization, gross morphology, tissue damage and inflammatory markers. WT strain PAO1 and its isogenic mutant PAO-JP2, in which both the lasI and rhlI quorum-sensing signal systems have been silenced, were compared during both acute and chronic prostate infections. In acute infections, bacterial numbers and inflammatory markers were comparable between WT PA01 and PAO-JP2; however, considerably less tissue damage occurred in infections with PAO-JP2. Chronic infections with PAO-JP2 resulted in reduced bacterial colonization, tissue damage and inflammation as compared to WT PAO1 infections. Therefore, the quorum-sensing lasI and rhlI genes in Ps. aeruginosa affect acute prostate infections, but play a considerably more important role in maintaining chronic infections. We have thus developed a highly reproducible model for the study of Ps. aeruginosa virulence in the prostate.

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Overproduction of the AlgT Sigma Factor Is Lethal to Mucoid Pseudomonas aeruginosa

Journal of Bacteriology ◽

10.1128/jb.00445-20 ◽

2020 ◽

Vol 202 (20) ◽

Cited By ~ 1

Author(s):

Ashley R. Cross ◽

Vishnu Raghuram ◽

Zihuan Wang ◽

Debayan Dey ◽

Joanna B. Goldberg

Keyword(s):

Pseudomonas Aeruginosa ◽

Sigma Factor ◽

Continuous Production ◽

Common Mutation ◽

Wild Type ◽

Chronic Infections ◽

Truncated Form ◽

Content Type ◽

Lung Infections

ABSTRACT Pseudomonas aeruginosa isolates from chronic lung infections often overproduce alginate, giving rise to the mucoid phenotype. Isolation of mucoid strains from chronic lung infections correlates with a poor patient outcome. The most common mutation that causes the mucoid phenotype is called mucA22 and results in a truncated form of the anti-sigma factor MucA that is continuously subjected to proteolysis. When a functional MucA is absent, the cognate sigma factor, AlgT, is no longer sequestered and continuously transcribes the alginate biosynthesis operon, leading to alginate overproduction. In this work, we report that in the absence of wild-type MucA, providing exogenous AlgT is toxic. This is intriguing, since mucoid strains endogenously possess high levels of AlgT. Furthermore, we show that suppressors of toxic AlgT production have mutations in mucP, a protease involved in MucA degradation, and provide the first atomistic model of MucP. Based on our findings, we speculate that mutations in mucP stabilize the truncated form of MucA22, rendering it functional and therefore able to reduce toxicity by properly sequestering AlgT. IMPORTANCE Pseudomonas aeruginosa is an opportunistic bacterial pathogen capable of causing chronic lung infections. Phenotypes important for the long-term persistence and adaption to this unique lung ecosystem are largely regulated by the AlgT sigma factor. Chronic infection isolates often contain mutations in the anti-sigma factor mucA, resulting in uncontrolled AlgT and continuous production of alginate in addition to the expression of ∼300 additional genes. Here, we report that in the absence of wild-type MucA, AlgT overproduction is lethal and that suppressors of toxic AlgT production have mutations in the MucA protease, MucP. Since AlgT contributes to the establishment of chronic infections, understanding how AlgT is regulated will provide vital information on how P. aeruginosa is capable of causing long-term infections.

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GidA Posttranscriptionally Regulates rhl Quorum Sensing in Pseudomonas aeruginosa

Journal of Bacteriology ◽

10.1128/jb.00335-09 ◽

2009 ◽

Vol 191 (18) ◽

pp. 5785-5792 ◽

Cited By ~ 31

Author(s):

Rashmi Gupta ◽

Timothy R. Gobble ◽

Martin Schuster

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Flavin Adenine Dinucleotide ◽

Skim Milk ◽

Opportunistic Pathogen ◽

Homoserine Lactone ◽

Trna Modification ◽

Loss Of Function ◽

Novel Genes ◽

Lasa Protease

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa utilizes two interconnected acyl-homoserine lactone quorum-sensing (acyl-HSL QS) systems, LasRI and RhlRI, to regulate the expression of hundreds of genes. The QS circuitry itself is integrated into a complex network of regulation by other factors. However, our understanding of this network is still unlikely to be complete, as a comprehensive, saturating approach to identifying regulatory components has never been attempted. Here, we utilized a nonredundant P. aeruginosa PA14 transposon library to identify additional genes that regulate QS at the level of LasRI/RhlRI. We initially screened all 5,459 mutants for loss of function in one QS-controlled trait (skim milk proteolysis) and then rescreened attenuated candidates for defects in other QS phenotypes (LasA protease, rhamnolipid, and pyocyanin production) to exclude mutants defective in functions other than QS. We identified several known and novel genes, but only two novel genes, gidA and pcnB, affected all of the traits assayed. We characterized gidA, which exhibited the most striking QS phenotypes, further. This gene is predicted to encode a conserved flavin adenine dinucleotide-binding protein involved in tRNA modification. Inactivation of the gene primarily affected rhlR-dependent QS phenotypes such as LasA, pyocyanin, and rhamnolipid production. GidA affected RhlR protein but not transcript levels and also had no impact on LasR and acyl-HSL production. Overexpression of rhlR in a gidA mutant partially restored QS-dependent phenotypes. Taken together, these results indicate that GidA selectively controls QS gene expression posttranscriptionally via RhlR-dependent and -independent pathways.

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Phenylacetyl Coenzyme A, Not Phenylacetic Acid, Attenuates CepIR-Regulated Virulence in Burkholderia cenocepacia

Applied and Environmental Microbiology ◽

10.1128/aem.01594-19 ◽

2019 ◽

Vol 85 (24) ◽

Author(s):

Tasia Joy Lightly ◽

Kara L. Frejuk ◽

Marie-Christine Groleau ◽

Laurent R. Chiarelli ◽

Cor Ras ◽

...

Keyword(s):

Quorum Sensing ◽

Phenylacetic Acid ◽

Coenzyme A ◽

Opportunistic Pathogen ◽

Burkholderia Cenocepacia ◽

Signal Molecules ◽

Wild Type ◽

Content Type ◽

Opportunistic Bacteria ◽

Virulent Phenotype

ABSTRACT During phenylalanine catabolism, phenylacetic acid (PAA) is converted to phenylacetyl coenzyme A (PAA-CoA) by a ligase, PaaK, and then PAA-CoA is epoxidized by a multicomponent monooxygenase, PaaABCDE, before further degradation through the tricarboxylic acid (TCA) cycle. In the opportunistic pathogen Burkholderia cenocepacia, loss of paaABCDE attenuates virulence factor expression, which is under the control of the LuxIR-like quorum sensing (QS) system, CepIR. To further investigate the link between CepIR-regulated virulence and PAA catabolism, we created knockout mutants of the first step of the pathway (PAA-CoA synthesis by PaaK) and characterized them in comparison to a paaABCDE mutant using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and virulence assays. We found that while loss of PaaABCDE decreased virulence, deletion of the paaK genes resulted in a more virulent phenotype than that of the wild-type strain. Deletion of either paaK or paaABCDE led to higher levels of released PAA but no differences in levels of internal accumulation compared to the wild-type level. While we found no evidence of direct cepIR downregulation by PAA-CoA or PAA, a low-virulence cepR mutant reverted to a virulent phenotype upon removal of the paaK genes. On the other hand, removal of paaABCDE in the cepR mutant did not impact its attenuated phenotype. Together, our results suggest an indirect role for PAA-CoA in suppressing B. cenocepacia CepIR-activated virulence. IMPORTANCE The opportunistic pathogen Burkholderia cenocepacia uses a chemical signal process called quorum sensing (QS) to produce virulence factors. In B. cenocepacia, QS relies on the presence of the transcriptional regulator CepR which, upon binding QS signal molecules, activates virulence. In this work, we found that even in the absence of CepR, B. cenocepacia can elicit a pathogenic response if phenylacetyl-CoA, an intermediate of the phenylacetic acid degradation pathway, is not produced. Instead, accumulation of phenylacetyl-CoA appears to attenuate pathogenicity. Therefore, we have discovered that it is possible to trigger virulence in the absence of CepR, challenging the classical view of activation of virulence by this QS mechanism. Our work provides new insight into the relationship between metabolism and virulence in opportunistic bacteria. We propose that in the event that QS signaling molecules cannot accumulate to trigger a pathogenic response, a metabolic signal can still activate virulence in B. cenocepacia.

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PrtR Homeostasis Contributes to Pseudomonas aeruginosa Pathogenesis and Resistance against Ciprofloxacin

Infection and Immunity ◽

10.1128/iai.01388-13 ◽

2014 ◽

Vol 82 (4) ◽

pp. 1638-1647 ◽

Cited By ~ 28

Author(s):

Ziyu Sun ◽

Jing Shi ◽

Chang Liu ◽

Yongxin Jin ◽

Kewei Li ◽

...

Keyword(s):

Gene Expression ◽

Pseudomonas Aeruginosa ◽

Bacterial Colonization ◽

Mrna Level ◽

Sos Response ◽

Opportunistic Pathogen ◽

Host Cells ◽

Chronic Infections ◽

Mobility Shift ◽

Content Type

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that causes acute and chronic infections in humans. Pyocins are bacteriocins produced byP. aeruginosathat are usually released through lysis of the producer strains. Expression of pyocin genes is negatively regulated by PrtR, which gets cleaved under SOS response, leading to upregulation of pyocin synthetic genes. Previously, we demonstrated that PrtR is required for the expression of type III secretion system (T3SS), which is an important virulence component ofP. aeruginosa. In this study, we demonstrate that mutation inprtRresults in reduced bacterial colonization in a mouse acute pneumonia model. Examination of bacterial and host cells in the bronchoalveolar lavage fluids from infected mice revealed that expression of PrtR is induced by reactive oxygen species (ROS) released by neutrophils. We further demonstrate that treatment with hydrogen peroxide or ciprofloxacin, known to induce the SOS response and pyocin production, resulted in an elevated PrtR mRNA level. Overexpression of PrtR by atacpromoter repressed the endogenousprtRpromoter activity, and electrophoretic mobility shift assay revealed that PrtR binds to its own promoter, suggesting an autorepressive mechanism of regulation. A high level of PrtR expressed from a plasmid resulted in increased T3SS gene expression during infection and higher resistance against ciprofloxacin. Overall, our results suggest that the autorepression of PrtR contributes to the maintenance of a relatively stable level of PrtR, which is permissive to T3SS gene expression in the presence of ROS while increasing bacterial tolerance to stresses, such as ciprofloxacin, by limiting pyocin production.

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TheprrF-Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

Infection and Immunity ◽

10.1128/iai.02707-14 ◽

2014 ◽

Vol 83 (3) ◽

pp. 863-875 ◽

Cited By ~ 41

Author(s):

Alexandria A. Reinhart ◽

Daniel A. Powell ◽

Angela T. Nguyen ◽

Maura O'Neill ◽

Louise Djapgne ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Iron Homeostasis ◽

Opportunistic Pathogen ◽

Wild Type ◽

Content Type ◽

Genes Encoding ◽

Small Regulatory Rnas ◽

Regulatory Rnas ◽

Heme Regulation ◽

Heme Binding Protein

Pseudomonas aeruginosais an opportunistic pathogen that requires iron to cause infection, but it also must regulate the uptake of iron to avoid iron toxicity. The iron-responsive PrrF1 and PrrF2 small regulatory RNAs (sRNAs) are part ofP. aeruginosa'siron regulatory network and affect the expression of at least 50 genes encoding iron-containing proteins. The genes encoding the PrrF1 and PrrF2 sRNAs are encoded in tandem inP. aeruginosa, allowing for the expression of a distinct, heme-responsive sRNA named PrrH that appears to regulate genes involved in heme metabolism. Using a combination of growth, mass spectrometry, and gene expression analysis, we showed that the ΔprrF1,2mutant, which lacks expression of the PrrF and PrrH sRNAs, is defective for both iron and heme homeostasis. We also identifiedphuS, encoding a heme binding protein involved in heme acquisition, andvreR, encoding a previously identified regulator ofP. aeruginosavirulence genes, as novel targets ofprrF-mediated heme regulation. Finally, we showed that theprrFlocus encoding the PrrF and PrrH sRNAs is required forP. aeruginosavirulence in a murine model of acute lung infection. Moreover, we showed that inoculation with a ΔprrF1,2deletion mutant protects against future challenge with wild-typeP. aeruginosa. Combined, these data demonstrate that theprrF-encoded sRNAs are critical regulators ofP. aeruginosavirulence.

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Loss of RNA Chaperone Hfq Unveils a Toxic Pathway in Pseudomonas aeruginosa

Journal of Bacteriology ◽

10.1128/jb.00232-19 ◽

2019 ◽

Vol 201 (20) ◽

Cited By ~ 2

Author(s):

Ian T. Hill ◽

Thomas Tallo ◽

Matthew J. Dorman ◽

Simon L. Dove

Keyword(s):

Pseudomonas Aeruginosa ◽

Opportunistic Pathogen ◽

Toxic Effects ◽

Growth Defect ◽

Wild Type ◽

Rna Chaperone ◽

Small Protein ◽

Content Type ◽

Transcription Regulator ◽

Mutant Cells

ABSTRACT Hfq is an RNA chaperone that serves as a master regulator of bacterial physiology. Here we show that in the opportunistic pathogen Pseudomonas aeruginosa, the loss of Hfq can result in a dramatic reduction in growth in a manner that is dependent upon MexT, a transcription regulator that governs antibiotic resistance in this organism. Using a combination of chromatin immunoprecipitation with high-throughput sequencing and transposon insertion sequencing, we identify the MexT-activated genes responsible for mediating the growth defect of hfq mutant cells. These include a newly identified MexT-controlled gene that we call hilR. We demonstrate that hilR encodes a small protein that is acutely toxic to wild-type cells when produced ectopically. Furthermore, we show that hilR expression is negatively regulated by Hfq, offering a possible explanation for the growth defect of hfq mutant cells. Finally, we present evidence that the expression of MexT-activated genes is dependent upon GshA, an enzyme involved in the synthesis of glutathione. Our findings suggest that Hfq can influence the growth of P. aeruginosa by limiting the toxic effects of specific MexT-regulated genes. Moreover, our results identify glutathione to be a factor important for the in vivo activity of MexT. IMPORTANCE Here we show that the conserved RNA chaperone Hfq is important for the growth of the opportunistic pathogen Pseudomonas aeruginosa. We found that the growth defect of hfq mutant cells is dependent upon the expression of genes that are under the control of the transcription regulator MexT. These include a gene that we refer to as hilR, which we show is negatively regulated by Hfq and encodes a small protein that can be toxic when ectopically produced in wild-type cells. Thus, Hfq can influence the growth of P. aeruginosa by limiting the toxic effects of MexT-regulated genes, including one encoding a previously unrecognized small protein. We also show that MexT activity depends on an enzyme that synthesizes glutathione.

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Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic Human Pathogen Pseudomonas aeruginosa

Journal of Bacteriology ◽

10.1128/jb.02557-14 ◽

2015 ◽

Vol 197 (12) ◽

pp. 2072-2082 ◽

Cited By ~ 46

Author(s):

Peter W. Davenport ◽

Julian L. Griffin ◽

Martin Welch

Keyword(s):

Pseudomonas Aeruginosa ◽

Fatty Acid ◽

Quorum Sensing ◽

Acid Methyl Ester ◽

Metabolic Changes ◽

Human Pathogen ◽

Wild Type ◽

Content Type ◽

Ecological Fitness ◽

Opportunistic Human Pathogen

ABSTRACTPseudomonas aeruginosausesN-acyl-homoserine lactone (AHL)-dependent quorum sensing (QS) systems to control the expression of secreted effectors. These effectors can be crucial to the ecological fitness of the bacterium, playing roles in nutrient acquisition, microbial competition, and virulence. In this study, we investigated the metabolic consequences of AHL-dependent QS by monitoring the metabolic profile(s) of alasI rhlIdouble mutant (unable to make QS signaling molecules) and its wild-type progenitor as they progressed through the growth curve. Analysis of culture supernatants by1H-nuclear magnetic resonance (1H-NMR) spectroscopy revealed that at the point where AHL concentrations peaked in the wild type, the metabolic footprints (i.e., extracellular metabolites) of the wild-type andlasI rhlImutant diverged. Subsequent gas chromatography-mass spectrometry (GC-MS)-based analysis of the intracellular metabolome revealed QS-dependent perturbations in around one-third of all identified metabolites, including altered concentrations of tricarboxylic acid (TCA) cycle intermediates, amino acids, and fatty acids. Further targeted fatty acid methyl ester (FAME) GC-MS-based profiling of the cellular total fatty acid pools revealed that QS leads to changes associated with decreased membrane fluidity and higher chemical stability. However, not all of the changes we observed were necessarily a direct consequence of QS; liquid chromatography (LC)-MS analyses revealed that polyamine levels were elevated in thelasI rhlImutant, perhaps a response to the absence of QS-dependent adaptations. Our data suggest that QS leads to a global readjustment in central metabolism and provide new insight into the metabolic changes associated with QS during stationary-phase adaptation.IMPORTANCEQuorum sensing (QS) is a transcriptional regulatory mechanism that allows bacteria to coordinate their gene expression profile with the population cell density. The opportunistic human pathogenPseudomonas aeruginosauses QS to control the production of secreted virulence factors. In this study, we show that QS elicits a global “metabolic rewiring” inP. aeruginosa. This metabolic rerouting of fluxes is consistent with a variety of drivers, ranging from altered QS-dependent transcription of “metabolic genes” through to the effect(s) of global “metabolic readjustment” as a consequence of QS-dependent exoproduct synthesis, as well as a general stress response, among others. To our knowledge, this is the first study of its kind to assess the global impact of QS on the metabolome.

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Scnn1b-Transgenic BALB/c Mice as a Model of Pseudomonas aeruginosa Infections of the Cystic Fibrosis Lung

Infection and Immunity ◽

10.1128/iai.00237-20 ◽

2020 ◽

Vol 88 (9) ◽

Author(s):

Kristen J. Brao ◽

Brendan P. Wille ◽

Joshua Lieberman ◽

Robert K. Ernst ◽

Mark E. Shirtliff ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Immune Cell ◽

Opportunistic Pathogen ◽

Sodium Absorption ◽

Lung Pathology ◽

Wild Type ◽

Content Type ◽

Lung Infections ◽

Content Modeling

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa is responsible for much of the morbidity and mortality associated with cystic fibrosis (CF), a condition that predisposes patients to chronic lung infections. P. aeruginosa lung infections are difficult to treat because P. aeruginosa adapts to the CF lung, can develop multidrug resistance, and can form biofilms. Despite the clinical significance of P. aeruginosa, modeling P. aeruginosa infections in CF has been challenging. Here, we characterize Scnn1b-transgenic (Tg) BALB/c mice as P. aeruginosa lung infection models. Scnn1b-Tg mice overexpress the epithelial Na+ channel (ENaC) in their lungs, driving increased sodium absorption that causes lung pathology similar to CF. We intranasally infected Scnn1b-Tg mice and wild-type littermates with the laboratory P. aeruginosa strain PAO1 and CF clinical isolates and then assessed differences in bacterial clearance, cytokine responses, and histological features up to 12 days postinfection. Scnn1b-Tg mice carried higher bacterial burdens when infected with biofilm-grown rather than planktonic PAO1; Scnn1b-Tg mice also cleared infections more slowly than their wild-type littermates. Infection with PAO1 elicited significant increases in proinflammatory and Th17-linked cytokines on day 3. Scnn1b-Tg mice infected with nonmucoid early CF isolates maintained bacterial burdens and mounted immune responses similar to those of PAO1-infected Scnn1b-Tg mice. In contrast, Scnn1b-Tg mice infected with a mucoid CF isolate carried high bacterial burdens, produced significantly more interleukin 1β (IL-1β), IL-13, IL-17, IL-22, and KC, and showed severe immune cell infiltration into the bronchioles. Taken together, these results show the promise of Scnn1b-Tg mice as models of early P. aeruginosa colonization in the CF lung.

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