Long-term coexistence of Pseudomonas aeruginosa and Staphylococcus aureus using an in vitro cystic fibrosis model

2021 ◽  
Author(s):  
Rosana Monteiro ◽  
Andreia Patrícia Magalhães ◽  
Maria Olivia Pereira ◽  
Ana Margarida Sousa
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physicochemical Characteristics ◽  
Antibiotic Tolerance ◽  
Virulence Potential ◽  
Cystic Fibrosis Airway ◽  
Lung Colonization

Aim: To investigate the role of pre-established Staphylococcus aureus on Pseudomonas aeruginosa adaptation and antibiotic tolerance. Materials & methods: Bacteria were cultured mimicking the sequential pattern of lung colonization and exposure to ciprofloxacin. Results: In the absence of ciprofloxacin exposure, S. aureus and P. aeruginosa coexisted supported by the physicochemical characteristics of the artificial sputum medium. S. aureus had no role in P. aeruginosa tolerance against ciprofloxacin and did not select P. aeruginosa small-colony variants during antibiotic treatment. rhlR and psqE were downregulated after the contact with S. aureus indicating that P. aeruginosa attenuated its virulence potential. Conclusion: P. aeruginosa and S. aureus can cohabit in cystic fibrosis airway environment for long-term without significant impact on P. aeruginosa adaptation and antibiotic tolerance.

scholarly journals Most of Staphylococcus aureus and Pseudomonas aeruginosa co-infecting isolates coexist, a condition that may impact clinical outcomes in Cystic Fibrosis patients

2020 ◽  
Author(s):  
Paul Briaud ◽  
Sylvère Bastien ◽  
Laura Camus ◽  
Marie Boyadjian ◽  
Philippe Reix ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Multivariate Analysis ◽  
Natural History ◽  
Clinical Outcomes ◽  
Bacterial Colonization ◽  
Childhood And Adolescence ◽  
History Of

AbstractStaphylococcus aureus (SA) is the major colonizer of the lung of cystic fibrosis (CF) patient during childhood and adolescence. As patient aged, the prevalence of SA decreases and Pseudomonas aeruginosa (PA) becomes the major pathogen infecting adult lungs. Nonetheless, SA remains significant and patients harbouring both SA and PA are frequently found in worldwide cohort. Impact of coinfection remains controversial. Furthermore, co-infecting isolates may compete or coexist. The aim of this study was to analyse if co-infection and coexistence of SA and PA could lead to worse clinical outcomes. The clinical and bacteriological data of 212 Lyon CF patients were collected retrospectively, and patients were ranked into three groups, SA only (n=112), PA only (n=48) or SA plus PA (n=52). In addition, SA and PA isolates from co-infecting patients were tested in vitro to define their interaction profile. Sixty five percent (n=34) of SA/PA pairs coexist. Using univariate and multivariate analysis, we confirm that SA patients have a clinical condition less severe than others, and PA induce a poor outcome independently of the presence of SA. FEV1 is lower in patients infected by competition strain pairs than in those infected by coexisting strain pairs compared to SA mono-infection. Coexistence between SA and PA may be an important step in the natural history of lung bacterial colonization within CF patients.

Evaluation of the Antimicrobial Efficacy of Urinary Catheters Impregnated With Antiseptics in an In Vitro Urinary Tract Model

2003 ◽  
Vol 24 (7) ◽  
pp. 506-513 ◽  
Author(s):  
Trupti A. Gaonkar ◽  
Lester A. Sampath ◽  
Shanta M. Modak
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Staphylococcus Epidermidis ◽  
Bacterial Colonization ◽  
Silver Sulfadiazine ◽  
Antimicrobial Spectrum

AbstractObjectives:To evaluate the long-term efficacy of urinary Foley catheters (latex and silicone) impregnated with (1) chlorhexidine and silver sulfadiazine (CXS) and (2) chlorhexidine, silver sulfadiazine, and triclosan (CXST) in inhibiting extra-luminal bacterial adherence and to compare their efficacy with that of silver hydrogel latex (SH) and nitrofurazone-treated silicone (NF) catheters.Design:The antimicrobial spectrum of these catheters was evaluated using a zone of inhibition assay. A novel in vitro urinary tract model was developed to study the potential in vivo efficacy of antimicrobial catheters in preventing extraluminal bacterial colonization. The “meatus” was inoculated daily with Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans. The “bladder” portion of the model was cultured daily to determine bacterial growth.Results:Both CXS and CXST catheters had a broader antimicrobial spectrum than SH and NF catheters. In the in vitro model, CXST latex and silicone catheters exhibited significantly better efficacy (3 to 25 days) against uropathogens, compared with CXS (1 to 14 days) and control (0 to 5 days) catheters (P = .01). CXST latex catheters exhibited significantly longer protection against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, compared with SH catheters (P = .01). CXST silicone catheters resisted colonization with Staphylococcus aureus and Staphylococcus epidermidis for a significantly longer period (23 to 24 days) than did NF catheters (9 to 11 days) (P = .01).Conclusion:Catheters impregnated with synergistic combinations of chlorhexidine, silver sulfadiazine, and triclosan exhibited broad-spectrum, long-term resistance against microbial colonization on their outer surfaces (Infect Control Hosp Epidemiol 2003;24:506-513)

scholarly journals Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Morgan T. Sutton ◽  
David Fletcher ◽  
Santosh K. Ghosh ◽  
Aaron Weinberg ◽  
Rolf van Heeckeren ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Bacterial Growth ◽  
Therapeutic Potential ◽  
Bioactive Molecules ◽  
Human Mscs ◽  
Antimicrobial Effectiveness

Cystic fibrosis (CF) is a genetic disease in which the battle between pulmonary infection and inflammation becomes the major cause of morbidity and mortality. We have previously shown that human MSCs (hMSCs) decrease inflammation and infection in thein vivomurine model of CF. The studies in this paper focus on the specificity of the hMSC antimicrobial effectiveness usingPseudomonas aeruginosa(gram negative bacteria) andStaphylococcus aureus(gram positive bacteria). Our studies show that hMSCs secrete bioactive molecules which are antimicrobialin vitroagainstPseudomonas aeruginosa, Staphylococcus aureus,andStreptococcus pneumonia, impacting the rate of bacterial growth and transition into colony forming units regardless of the pathogen. Further, we show that the hMSCs have the capacity to enhance antibiotic sensitivity, improving the capacity to kill bacteria. We present data which suggests that the antimicrobial effectiveness is associated with the capacity to slow bacterial growth and the ability of the hMSCs to secrete the antimicrobial peptide LL-37. Lastly, our studies demonstrate that the tissue origin of the hMSCs (bone marrow or adipose tissue derived), the presence of functional cystic fibrosis transmembrane conductance regulator (CFTR: human,Cftr: mouse) activity, and response to effector cytokines can impact both hMSC phenotype and antimicrobial potency and efficacy. These studies demonstrate, the unique capacity of the hMSCs to manage different pathogens and the significance of their phenotype in both the antimicrobial and antibiotic enhancing activities.

scholarly journals Polymicrobial Interactions in the Cystic Fibrosis Airway Microbiome Impact the Antimicrobial Susceptibility of Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 827
Author(s):  
Emma Reece ◽  
Pedro H. de Almeida Bettio ◽  
Julie Renwick
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Airway Disease ◽  
Chronic Infections ◽  
Sensitivity Testing ◽  
Antimicrobial Sensitivity ◽  
Cystic Fibrosis Airway ◽  
Airway Microbiome ◽  
Diverse Community

Pseudomonas aeruginosa is one of the most dominant pathogens in cystic fibrosis (CF) airway disease and contributes to significant inflammation, airway damage, and poorer disease outcomes. The CF airway is now known to be host to a complex community of microorganisms, and polymicrobial interactions have been shown to play an important role in shaping P. aeruginosa pathogenicity and resistance. P. aeruginosa can cause chronic infections that once established are almost impossible to eradicate with antibiotics. CF patients that develop chronic P. aeruginosa infection have poorer lung function, higher morbidity, and a reduced life expectancy. P. aeruginosa adapts to the CF airway and quickly develops resistance to several antibiotics. A perplexing phenomenon is the disparity between in vitro antimicrobial sensitivity testing and clinical response. Considering the CF airway is host to a diverse community of microorganisms or ‘microbiome’ and that these microorganisms are known to interact, the antimicrobial resistance and progression of P. aeruginosa infection is likely influenced by these microbial relationships. This review combines the literature to date on interactions between P. aeruginosa and other airway microorganisms and the influence of these interactions on P. aeruginosa tolerance to antimicrobials.

scholarly journals High virulence sub-populations in Pseudomonas aeruginosa long-term cystic fibrosis airway infections

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Siobhán O’Brien ◽  
David Williams ◽  
Joanne L. Fothergill ◽  
Steve Paterson ◽  
Craig Winstanley ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Cystic Fibrosis Airway ◽  
Airway Infections ◽  
High Virulence

scholarly journals The high persister phenotype ofPseudomonas aeruginosais associated with increased fitness and persistence in cystic fibrosis airways

2019 ◽  
Author(s):  
Biljana Mojsoska ◽  
David R. Cameron ◽  
Jennifer A. Bartell ◽  
Janus Anders Juul Haagensen ◽  
Lea M. Sommer ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Genetic Alterations ◽  
Antibiotic Tolerance ◽  
High Throughput Screening Assay ◽  
The Impact ◽  
Over Time ◽  
Better Than

AbstractDespite intensive antibiotic treatment of cystic fibrosis (CF) patients,Pseudomonas aeruginosaoften persists in patient airways for decades, and can do so without the development of antibiotic resistance. Using a high-throughput screening assay of survival after treatment with high concentrations of ciprofloxacin, we have determined the prevalence of high-persister variants (Hip) in a large patient cohort. In a screen of 467 longitudinal clinical isolates ofP. aeruginosafrom 40 CF patients, we classified 25.7% as Hip. Hip were identified in 26 patients, but only a few bacterial lineages were dominated by Hip. Instead, the emergence of Hip increased over time, suggesting that CF airways treated with ciprofloxacin select for Hip with an increased fitness in this environment. We generally observed diverse genetic changes in the Hip isolate population (as many co-occurring routes to increased fitness exist), but interestingly elevated mutation counts in the RpoN gene of 18 Hip isolates suggest that this sigma factor plays a role in shaping levels of antibiotic tolerance. To probe the impact of the Hip phenotype in a CF-similar environment, we tested the fitness properties of otherwise genotypically and phenotypically similar low-persister (Lop) and Hip isolates in co-culture using a specialized flow-cell biofilm system mimicking pharmacokinetic/-dynamic antibiotic dosing. Hip survived ciprofloxacin treatment far better than Lop isolates. The results of this investigation provide novel insights into persister dynamics and fitness contributions to survival in the CF lung, and show that the Hip phenotype of antibiotic susceptible bacteria plays an important role in long-term infections.SignificanceAntibiotic resistance is emphasized as a rapidly increasing health threat, but antibiotic tolerance via the occurrence of persister cells in antibiotic-treated bacterial populations is clinically and publicly neglected. In 40 CF patients representing a well-established human infection model – long-term lung infections byPseudomonas aeruginosa– we show the emergence and accumulation of persister variants in a clinical population heavily reliant on antibiotic therapy. We observe that the high-persister (Hip) phenotype is independent of resistance and likely the consequence of numerous genetic alterations, complicating surveillance and inhibition in the clinic. Furthermore, we find Hip are selected for over time, survive better than ‘normal’ bacteria, and can outcompete them in CF-similar conditions, ultimately affecting 65% of patients in an early disease cohort.

scholarly journals Coculture of Staphylococcus aureus with Pseudomonas aeruginosa Drives S. aureus towards Fermentative Metabolism and Reduced Viability in a Cystic Fibrosis Model

2015 ◽  
Vol 197 (14) ◽  
pp. 2252-2264 ◽  
Author(s):  
Laura M. Filkins ◽  
Jyoti A. Graber ◽  
Daniel G. Olson ◽  
Emily L. Dolben ◽  
Lee R. Lynd ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Early Adulthood ◽  
Aerobic Respiration ◽  
Dependent Manner ◽  
Microbial Composition ◽  
Content Type ◽  
Coculture System

ABSTRACTThe airways of patients with cystic fibrosis are colonized with diverse bacterial communities that change dynamically during pediatric years and early adulthood.Staphylococcus aureusis the most prevalent pathogen during early childhood, but during late teens and early adulthood, a shift in microbial composition occurs leading toPseudomonas aeruginosacommunity predominance in ∼50% of adults. We developed a robust dual-bacterialin vitrococulture system ofP. aeruginosaandS. aureuson monolayers of human bronchial epithelial cells homozygous for the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) mutation to better model the mechanisms of this interaction. We show thatP. aeruginosadrives theS. aureusexpression profile from that of aerobic respiration to fermentation. This shift is dependent on the production of both 2-heptyl-4-hydroxyquinolineN-oxide (HQNO) and siderophores byP. aeruginosa. Furthermore,S. aureus-produced lactate is a carbon source thatP. aeruginosapreferentially consumes over medium-supplied glucose. We find that initiallyS. aureusandP. aeruginosacoexist; however, over extended cocultureP. aeruginosareducesS. aureusviability, also in an HQNO- andP. aeruginosasiderophore-dependent manner. Interestingly,S. aureussmall-colony-variant (SCV) genetic mutant strains, which have defects in their electron transport chain, experience reduced killing byP. aeruginosacompared to their wild-type parent strains; thus, SCVs may provide a mechanism for persistence ofS. aureusin the presence ofP. aeruginosa. We propose that the mechanism ofP. aeruginosa-mediated killing ofS. aureusis multifactorial, requiring HQNO andP. aeruginosasiderophores as well as additional genetic, environmental, and nutritional factors.IMPORTANCEIn individuals with cystic fibrosis,Staphylococcus aureusis the primary respiratory pathogen during childhood. During adulthood,Pseudomonas aeruginosapredominates and correlates with worse patient outcome. The mechanism(s) by whichP. aeruginosaoutcompetes or killsS. aureusis not well understood. We describe anin vitrodual-bacterial species coculture system on cystic fibrosis-derived airway cells, which models interactions relevant to patients with cystic fibrosis. Further, we show that molecules produced byP. aeruginosaadditively induce a transition ofS. aureusmetabolism from aerobic respiration to fermentation and eventually lead to loss ofS. aureusviability. Elucidating the molecular mechanisms ofP. aeruginosacommunity predominance can provide new therapeutic targets and approaches to impede this microbial community transition and subsequent patient worsening.

scholarly journals Adaptation of Pseudomonas aeruginosa in Cystic Fibrosis Airways Influences Virulence of Staphylococcus aureus In Vitro and Murine Models of Co-Infection

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e89614 ◽  
Author(s):  
Rossella Baldan ◽  
Cristina Cigana ◽  
Francesca Testa ◽  
Irene Bianconi ◽  
Maura De Simone ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Murine Models

scholarly journals Association of Diverse Staphylococcus aureus Populations with Pseudomonas aeruginosa Coinfection and Inflammation in Cystic Fibrosis Airway Infection

mSphere ◽  
2021 ◽  
Author(s):  
Marie K. Wieneke ◽  
Felix Dach ◽  
Claudia Neumann ◽  
Dennis Görlich ◽  
Lena Kaese ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Therapy ◽  
Content Type ◽  
Airway Infection ◽  
Cystic Fibrosis Airway

Staphylococcus aureus can persist for extended periods in the airways of people with cystic fibrosis (CF) in spite of antibiotic therapy and high numbers of neutrophils, which fail to eradicate this pathogen. Therefore, S. aureus needs to adapt to this hostile niche.

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