scholarly journals Biological Markers of Pseudomonas aeruginosa Epidemic High-Risk Clones

2013 ◽  
Vol 57 (11) ◽  
pp. 5527-5535 ◽  
Author(s):  
Xavier Mulet ◽  
Gabriel Cabot ◽  
Alain A. Ocampo-Sosa ◽  
M. Angeles Domínguez ◽  
Laura Zamorano ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Multicenter Study ◽  
Biological Markers ◽  
Biofilm Formation ◽  
Specific Treatment ◽  
Spontaneous Mutant ◽  
Biological Parameters ◽  
Content Type

ABSTRACTA limited number ofPseudomonas aeruginosagenotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study ofP. aeruginosabloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n= 6], ST-111 [n= 7], and ST-235 [n= 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and thein vitrocompetition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies.

scholarly journals Tobramycin-Treated Pseudomonas aeruginosa PA14 Enhances Streptococcus constellatus 7155 Biofilm Formation in a Cystic Fibrosis Model System

2015 ◽  
Vol 198 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Katherine E. Price ◽  
Amanda A. Naimie ◽  
Edward F. Griffin ◽  
Charles Bay ◽  
George A. O'Toole
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Deep Sequencing ◽  
Biofilm Formation ◽  
Interspecies Interaction ◽  
Content Type ◽  
Streptococcus Constellatus ◽  
Sequencing Studies ◽  
Airway Cells

ABSTRACTCystic fibrosis (CF) is a human genetic disorder which results in a lung environment that is highly conducive to chronic microbial infection. Over the past decade, deep-sequencing studies have demonstrated that the CF lung can harbor a highly diverse polymicrobial community. We expanded our existingin vitromodel ofPseudomonas aeruginosabiofilm formation on CF-derived airway cells to include this broader set of CF airway colonizers to investigate their contributions to CF lung disease, particularly as they relate to the antibiotic response of the population. Using this system, we identified an interspecies interaction betweenP. aeruginosa, a bacterium associated with declining lung function and worsening disease, andStreptococcus constellatus, a bacterium correlated with the onset of pulmonary exacerbations in CF patients. The growth rate and cytotoxicity ofS. constellatus7155 andP. aeruginosaPA14 were unchanged when grown together as mixed biofilms in the absence of antibiotics. However, the addition of tobramycin, the frontline maintenance therapy antibiotic for individuals with CF, to a mixed biofilm ofS. constellatus7155 andP. aeruginosaPA14 resulted in enhancedS. constellatusbiofilm formation. Through a candidate genetic approach, we showed thatP. aeruginosarhamnolipids were reduced upon tobramycin exposure, allowing forS. constellatus7155 biofilm enhancement, and monorhamnolipids were sufficient to reduceS. constellatus7155 biofilm viability in the absence of tobramycin. While the findings presented here are specific to a biofilm ofS. constellatus7155 andP. aeruginosaPA14, they highlight the potential of polymicrobial interactions to impact antibiotic tolerance in unanticipated ways.IMPORTANCEDeep-sequencing studies have demonstrated that the CF lung can harbor a diverse polymicrobial community. By recapitulating the polymicrobial communities observed in the CF lung and identifying mechanisms of interspecies interactions, we have the potential to select the best therapy for a given bacterial community and reveal potential opportunities for novel therapeutic interventions. Using anin vitromodel of bacterial infection on CF airway cells, we tested how a particular polymicrobial community grows, damages human cells, and responds to antibiotics in single and mixed infections. We describe here the mechanism of an interspecies interaction between two pathogens in the CF lung,P. aeruginosaandS. constellatus, which is potentiated by a commonly prescribed antibiotic, tobramycin.

scholarly journals Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in an In Vitro Pharmacodynamic Model

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
María Montero ◽  
Sandra Domene Ochoa ◽  
Carla López-Causapé ◽  
Brian VanScoy ◽  
Sonia Luque ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Therapeutic Option ◽  
Drug Resistant ◽  
Chemostat Model ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Spanish Study ◽  
Time Kill

ABSTRACT Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of C/T and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and C/T alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa ST175 isolates with different susceptibility levels to C/T. Static time-kill assays demonstrated superior synergistic or additive effect for C/T plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. C/T plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high risk-clones resistant to C/T.

scholarly journals Catheter-Associated Urinary Tract Infection by Pseudomonas aeruginosa Is Mediated by Exopolysaccharide-Independent Biofilms

2014 ◽  
Vol 82 (5) ◽  
pp. 2048-2058 ◽  
Author(s):  
Stephanie J. Cole ◽  
Angela R. Records ◽  
Mona W. Orr ◽  
Sara B. Linden ◽  
Vincent T. Lee
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Biofilm Formation ◽  
Extracellular Dna ◽  
Extracellular Polysaccharides ◽  
Indwelling Catheters ◽  
Content Type ◽  
Tract Infections

ABSTRACTPseudomonas aeruginosais an opportunistic human pathogen that is especially adept at forming surface-associated biofilms.P. aeruginosacauses catheter-associated urinary tract infections (CAUTIs) through biofilm formation on the surface of indwelling catheters.P. aeruginosaencodes three extracellular polysaccharides, PEL, PSL, and alginate, and utilizes the PEL and PSL polysaccharides to form biofilmsin vitro; however, the requirement of these polysaccharides duringin vivoinfections is not well understood. Here we show in a murine model of CAUTI that PAO1, a strain harboringpel,psl, andalggenes, and PA14, a strain harboringpelandalggenes, form biofilms on the implanted catheters. To determine the requirement of exopolysaccharide duringin vivobiofilm infections, we tested isogenic mutants lacking thepel,psl, andalgoperons and showed that PA14 mutants lacking these operons can successfully form biofilms on catheters in the CAUTI model. To determine the host factor(s) that induces the ΔpelDmutant to form biofilm, we tested mouse, human, and artificial urine and show that urine can induce biofilm formation by the PA14 ΔpelDmutant. By testing the major constituents of urine, we show that urea can induce apel-,psl-, andalg-independent biofilm. Thesepel-,psl-, andalg-independent biofilms are mediated by the release of extracellular DNA. Treatment of biofilms formed in urea with DNase I reduced the biofilm, indicating that extracellular DNA supports biofilm formation. Our results indicate that the opportunistic pathogenP. aeruginosautilizes a distinct program to form biofilms that are independent of exopolysaccharides during CAUTI.

scholarly journals A Survival Strategy for Pseudomonas aeruginosa That Uses Exopolysaccharides To Sequester and Store Iron To Stimulate Psl-Dependent Biofilm Formation

2016 ◽  
Vol 82 (21) ◽  
pp. 6403-6413 ◽  
Author(s):  
Shan Yu ◽  
Qing Wei ◽  
Tianhu Zhao ◽  
Yuan Guo ◽  
Luyan Z. Ma
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Iron Concentration ◽  
Survival Strategy ◽  
Iron Storage ◽  
Content Type ◽  
High Level ◽  
Biofilm Development ◽  
Biofilm Matrix

ABSTRACTExopolysaccharide Psl is a critical biofilm matrix component inPseudomonas aeruginosa, which forms a fiber-like matrix to enmesh bacterial communities. Iron is important forP. aeruginosabiofilm development, yet it is not clearly understood how iron contributes to biofilm development. Here, we showed that iron promoted biofilm formation via elevating Psl production inP. aeruginosa. The high level of iron stimulated the synthesis of Psl by reducing rhamnolipid biosynthesis and inhibiting the expression of AmrZ, a repressor ofpslgenes. Iron-stimulated Psl biosynthesis and biofilm formation held true in mucoidP. aeruginosastrains. Subsequent experiments indicated that iron bound with Pslin vitroand in biofilms, which suggested that Psl fibers functioned as an iron storage channel inP. aeruginosabiofilms. Moreover, among three matrix exopolysaccharides ofP. aeruginosa, Psl is the only exopolysaccharide that can bind with both ferrous and ferric ion, yet with higher affinity for ferrous iron. Our data suggest a survival strategy ofP. aeruginosathat uses exopolysaccharide to sequester and store iron to stimulate Psl-dependent biofilm formation.IMPORTANCEPseudomonas aeruginosais an environmental microorganism which is also an opportunistic pathogen that can cause severe infections in immunocompromised individuals. It is the predominant airway pathogen causing morbidity and mortality in individuals affected by the genetic disease cystic fibrosis (CF). Increased airway iron and biofilm formation have been proposed to be the potential factors involved in the persistence ofP. aeruginosain CF patients. Here, we showed that a high level of iron enhanced the production of the key biofilm matrix exopolysaccharide Psl to stimulate Psl-dependent biofilm formation. Our results not only make the link between biofilm formation and iron concentration in CF, but also could guide the administration or use of iron chelators to interfere with biofilm formation inP. aeruginosain CF patients. Furthermore, our data also imply a survival strategy ofP. aeruginosaunder high-iron environmental conditions.

scholarly journals Bactericidal Activities of Cathelicidin LL-37 and Select Cationic Lipids against the Hypervirulent Pseudomonas aeruginosa Strain LESB58

2015 ◽  
Vol 59 (7) ◽  
pp. 3808-3815 ◽  
Author(s):  
Urszula Wnorowska ◽  
Katarzyna Niemirowicz ◽  
Melissa Myint ◽  
Scott L. Diamond ◽  
Marta Wróblewska ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Cationic Lipid ◽  
Antibacterial Activities ◽  
Cationic Lipids ◽  
Content Type ◽  
Patient Morbidity ◽  
Bactericidal Activities ◽  
Pf1 Bacteriophage

ABSTRACTPseudomonas aeruginosaLiverpool epidemic strain (LES) infections in cystic fibrosis (CF) patients are associated with transmissibility and increased patient morbidity. This study was designed to assess thein vitroactivities of cathelicidin LL-37 peptide (LL-37) and select cationic lipids againstPseudomonas aeruginosaLESB58 in CF sputum and in a setting mimicking the CF airway. We found that LL-37 naturally present in airway surface fluid and some nonpeptide cationic lipid molecules such as CSA-13, CSA-90, CSA-131, and D2S have significant, but broadly differing, bactericidal activities againstP. aeruginosaLESB58. We observed strong inhibition of LL-37 bactericidal activity in the presence of purified bacteriophage Pf1, which is highly expressed byP. aeruginosaLES, but the activities of the cationic lipids CSA-13 and CSA-131 were not affected by this polyanionic virus. Additionally, CSA-13 and CSA-131 effectively prevent LESB58 biofilm formation, which is stimulated by Pf1 bacteriophage, DNA, or F-actin. CSA-13 and CSA-131 display strong antibacterial activities against different clinical strains ofP. aeruginosa, and their activities againstP. aeruginosaLESB58 and Xen5 strains were maintained in CF sputum. These data indicate that synthetic cationic lipids (mimics of natural antimicrobial peptides) are suitable for developing an effective treatment against CF lungP. aeruginosainfections, including those caused by LES strains.

scholarly journals Pseudomonas aeruginosa biofilm formation on endotracheal tubes requires multiple two-component systems

2020 ◽  
Vol 69 (6) ◽  
pp. 906-919 ◽  
Author(s):  
Divakar Badal ◽  
Abhijith Vimal Jayarani ◽  
Mohammed Ameen Kollaran ◽  
Aloke Kumar ◽  
Varsha Singh
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Type Species ◽  
Content Type ◽  
Endotracheal Tubes ◽  
Link Type ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

Introduction. Indwelling medical devices such as endotracheal tubes (ETTs), urinary catheters, vascular access devices, tracheostomies and feeding tubes are often associated with hospital-acquired infections. Bacterial biofilm formed on the ETTs in intubated patients is a significant risk factor associated with ventilator-associated pneumonia. Pseudomonas aeruginosa is one of the four frequently encountered bacteria responsible for causing pneumonia, and the biofilm formation on ETTs. However, understanding of biofilm formation on ETT and interventions to prevent biofilm remains lagging. The ability to sense and adapt to external cues contributes to their success. Thus, the biofilm formation is likely to be influenced by the two-component systems (TCSs) that are composed of a membrane-associated sensor kinase and an intracellular response regulator. Aim. This study aims to establish an in vitro method to analyse the P. aeruginosa biofilm formation on ETTs, and identify the TCSs that contribute to this process. Methodology. In total, 112 P. aeruginosa PA14 TCS mutants were tested for their ability to form biofilm on ETTs, their effect on quorum sensing (QS) and motility. Results. Out of 112 TCS mutants studied, 56 had altered biofilm biomass on ETTs. Although the biofilm formation on ETTs is QS-dependent, none of the 56 loci controlled quorum signal. Of these, 18 novel TCSs specific to ETT biofilm were identified, namely, AauS, AgtS, ColR, CopS, CprR, NasT, KdpD, ParS, PmrB, PprA, PvrS, RcsC, PA14_11120, PA14_32580, PA14_45880, PA14_49420, PA14_52240, PA14_70790. The set of 56 included the GacS network, TCS proteins involved in fimbriae synthesis, TCS proteins involved in antimicrobial peptide resistance, and surface-sensing. Additionally, several of the TCS-encoding genes involved in biofilm formation on ETTs were found to be linked to flagellum-dependent swimming motility. Conclusions. Our study established an in vitro method for studying P. aeruginosa biofilm formation on the ETT surfaces. We also identified novel ETT-specific TCSs that could serve as targets to prevent biofilm formation on indwelling devices frequently used in clinical settings.

Bioactivity of Phenolic Compounds Extracted from Strawberry against Formation of Pseudomonas aeruginosa Biofilm

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Baydaa Hussein ◽  
Zainab A. Aldhaher ◽  
Shahrazad Najem Abdu-Allah ◽  
Adel Hamdan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phenolic Compounds ◽  
Biofilm Formation ◽  
Opportunistic Infections ◽  
Formation Rate ◽  
Hydrocarbon Chain ◽  
Health Concern ◽  
Gas Chromatography Mass Spectrometry ◽  
Phenolic Contents

Background: Biofilm is a bacterial way of life prevalent in the world of microbes; in addition to that it is a source of alarm in the field of health concern. Pseudomonas aeruginosa is a pathogenic bacterium responsible for all opportunistic infections such as chronic and severe. Aim of this study: This paper aims to provide an overview of the promotion of isolates to produce a biofilm in vitro under special circumstances, to expose certain antibiotics to produce phenotypic evaluation of biofilm bacteria. Methods and Materials: Three diverse ways were used to inhibited biofilm formation of P.aeruginosa by effect of phenolic compounds extracts from strawberries. Isolates produced biofilm on agar MacConkey under certain circumstances. Results: The results showed that all isolates were resistant to antibiotics except sensitive to azithromycin (AZM, 15μg), and in this study was conducted on three ways to detect the biofilm produced, has been detected by the biofilm like Tissue culture plate (TCP), Tube method (TM), Congo Red Agar (CRA). These methods gave a clear result of these isolates under study. Active compounds were analyzed in both extracts by Gas Chromatography-mass Spectrometry which indicate High molecular weight compound with a long hydrocarbon chain. Conclusion: Phenolic compounds could behave as bioactive material and can be useful to be used in pharmaceutical synthesis. Phenolic contents which found in leaves and fruits extracts of strawberries shows antibacterial activity against all strains tested by the ability to reduce the production of biofilm formation rate.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals An In Vitro Coumarin-Antibiotic Combination Treatment of Pseudomonas aeruginosa Biofilms

2021 ◽  
Vol 16 (1) ◽  
pp. 1934578X2098774
Author(s):  
Jinpeng Zou ◽  
Yang Liu ◽  
Ruiwei Guo ◽  
Yu Tang ◽  
Zhengrong Shi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Resistance ◽  
Combination Treatment ◽  
Crude Extract ◽  
Biofilm Formation ◽  
Bacterial Resistance ◽  
Antibacterial Properties ◽  
Biofilm Growth ◽  
Antibiotic Combination

The drug resistance of Pseudomonas aeruginosa is a worldwide problem due to its great threat to human health. A crude extract of Angelica dahurica has been proved to have antibacterial properties, which suggested that it may be able to inhibit the biofilm formation of P. aeruginosa; initial exploration had shown that the crude extract could inhibit the growth of P. aeruginosa effectively. After the adaptive dose of coumarin was confirmed to be a potential treatment for the bacteria’s drug resistance, “coumarin-antibiotic combination treatments” (3 coumarins—simple coumarin, imperatorin, and isoimperatorin—combined with 2 antibiotics—ampicillin and ceftazidime) were examined to determine their capability to inhibit P. aeruginosa. The final results showed that (1) coumarin with either ampicillin or ceftazidime significantly inhibited the biofilm formation of P. aeruginosa; (2) coumarin could directly destroy mature biofilms; and (3) the combination treatment can synergistically enhance the inhibition of biofilm formation, which could significantly reduce the usage of antibiotics and bacterial resistance. To sum up, a coumarin-antibiotic combination treatment may be a potential way to inhibit the biofilm growth of P. aeruginosa and provides a reference for antibiotic resistance treatment.

scholarly journals Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa

2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physical Space ◽  
Late Time ◽  
Protective Effects ◽  
Content Type ◽  
Alginate Production ◽  
The Impact

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

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