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 ◽  
...  
2020 ◽  
Author(s):  
Paul Briaud ◽  
Sylvère Bastien ◽  
Laura Camus ◽  
Marie Boyadjian ◽  
Philippe Reix ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Morgan T. Sutton ◽  
David Fletcher ◽  
Santosh K. Ghosh ◽  
Aaron Weinberg ◽  
Rolf van Heeckeren ◽  
...  

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.


2021 ◽  
Author(s):  
Rosana Monteiro ◽  
Andreia Patrícia Magalhães ◽  
Maria Olivia Pereira ◽  
Ana Margarida Sousa

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.


2015 ◽  
Vol 197 (14) ◽  
pp. 2252-2264 ◽  
Author(s):  
Laura M. Filkins ◽  
Jyoti A. Graber ◽  
Daniel G. Olson ◽  
Emily L. Dolben ◽  
Lee R. Lynd ◽  
...  

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.


Author(s):  
Karlynne Freire Mendonça ◽  
José Klauber Roger Carneiro ◽  
Maria Auxiliadora Silva Oliveira

Objetivos: avaliar a atividade antimicrobiana em extrato aquoso, hidroalcoólico e alcoólico das folhas de espécies da família Lamiaceae frente a bactérias de interesse. Método: Foram escolhidas quatro espécies: Ocimum gratissimum, Plectranthus amboinicus, Mentha arvensis e Plectranthus barbatus. A partir das folhas foram confeccionados os extratos aquoso, hidroalcoólico e alcoólico nas concentrações 100mg/mL, 50mg/mL e 25mg/mL. Foram selecionadas as bactérias Streptococcus pyogenes, Enterococcus faecalis, Staphylococcus aureus e Pseudomonas aeruginosa para os ensaios de antibiose em Ágar Mueller-Hinton. Resultados: P. barbatus, em seu extrato hidroalcoólico mostrou ativo nas três concentrações para bactéria S. aureus, e ainda foi ativo para P. aeruginosa, demonstrando no extrato alcoólico atividade frente as bactérias. Para M. arvensis e P. amboinicus, seus extratos hidroalcoólico e alcoólico apresentaram atividade para S. aureus. Conclusão: Sugere-se que as espécies em questão apresentem boa atividade antimicrobiana, sendo necessária a realização de mais estudos para melhor entender esse mecanismo.


2019 ◽  
Vol 17 (3) ◽  
pp. 140-148 ◽  
Author(s):  
A. Ouelhadj ◽  
L. Ait Salem ◽  
D. Djenane

Ce travail vise l’étude de l’activité antibactérienne de l’huile essentielle (HE) de Pelargoniumx asperum et de la bactériocine, la nisine seul et en combinaison vis-à-vis de six bactéries dont quatre sont multirésistantes d’origine clinique. L’activité antibactérienne in vitro a été évaluée par la méthode de diffusion sur gélose. La concentration minimale inhibitrice (CMI) est aussi déterminée pour HE. Les résultats ont révélé une activité antibactérienne significative exercée par HE visà-vis de Staphylococcus aureus (ATCC 43300), Staphylococcus aureus et Escherichia coli avec des diamètres d’inhibition de 36,00 ; 22,50 et 40,00 mm, respectivement. Cependant, l’HE de Pelargonium asperum a montré une activité antibactérienne supérieure par rapport à la nisine. Les valeurs des CMI rapportées dans cette étude sont comprises entre 1,98–3,96 μl/ml. Les combinaisons réalisées entre HE et la nisine ont montré un effet additif vis-à-vis de Escherichia coli (ATCC 25922) avec (50 % HE Pelargonium asperum + 50 % nisine). Par contre, nous avons enregistré une synergie vis-à-vis de Klebsiella pneumoniae avec (75 % HE Pelargonium asperum + 25 % nisine) et contre Pseudomonas aeruginosa avec les trois combinaisons testées. Les résultats obtenus permettent de dire que l’HE de Pelargonium asperum possède une activité antibactérienne ainsi que sa combinaison avec la nisine pourrait représenter une bonne alternative pour la lutte contre l’antibiorésistance.


Bionatura ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. 1335-1339
Author(s):  
Pool Marcos-Carbajal ◽  
Christian Allca-Muñoz ◽  
Ángel Urbano-Niño ◽  
Alberto Salazar-Granara

El objetivo del estudio es determinar la actividad antibacteriana de Metformina frente a Escherichia coli, Staphylococcus aureus y Pseudomonas aeruginosa. Se evaluó la actividad antibacteriana mediante la técnica de Kirby Bauer. Se utilizó cepas de Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923) y Pseudomonas aeruginosa (ATCC 27853), las cuales se expusieron a Metformina en concentraciones de 250 mg y 500 mg, Ciprofloxacino (CIP) 5 µg, Imipenem (IPM) 10 µg, y Cefoxitin (FOX) 30 µg. Frente a Escherichia coli, Staphylococcus aureus y Pseudomonas aeruginosa se presentó un halo de inhibición de 6 mm. para Metformina 250 mg, 6 mm. para Metformina 500 mg, y un halo de inhibición >25 mm. con el uso de Ciprofloxacino 5 µg, Cefoxitin 30 µg, e Imipenem 10 µg respectivamente. En conclusion, In vitro Metformina a dosis de 250 y 500 mg, no presentó efecto antibacteriano frente a Escherichia coli, Staphylococcus aureus y Pseudomonas aeruginosa.


2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole

ABSTRACT The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus. We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms. IMPORTANCE Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.


2019 ◽  
Vol 75 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Odel Soren ◽  
Ardeshir Rineh ◽  
Diogo G Silva ◽  
Yuming Cai ◽  
Robert P Howlin ◽  
...  

Abstract Objectives The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D (‘DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate’) has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. Methods β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. Results DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. Conclusions DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.


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