scholarly journals Sodium Nitrite-Mediated Killing of the Major Cystic Fibrosis Pathogens Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia under Anaerobic Planktonic and Biofilm Conditions

2010 ◽  
Vol 54 (11) ◽  
pp. 4671-4677 ◽  
Author(s):  
Tiffany A. Major ◽  
Warunya Panmanee ◽  
Joel E. Mortensen ◽  
Larry D. Gray ◽  
Niel Hoglen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Sodium Nitrite ◽  
Burkholderia Cepacia ◽  
Airway Disease ◽  
Resistant Organism ◽  
Anaerobic Conditions ◽  
Chronic Infections ◽  
Antibiotic Resistant

ABSTRACT A hallmark of airways in patients with cystic fibrosis (CF) is highly refractory, chronic infections by several opportunistic bacterial pathogens. A recent study demonstrated that acidified sodium nitrite (A-NO2 −) killed the highly refractory mucoid form of Pseudomonas aeruginosa, a pathogen that significantly compromises lung function in CF patients (S. S. Yoon et al., J. Clin. Invest. 116:436-446, 2006). Therefore, the microbicidal activity of A-NO2 − (pH 6.5) against the following three major CF pathogens was assessed: P. aeruginosa (a mucoid, mucA22 mutant and a sequenced nonmucoid strain, PAO1), Staphylococcus aureus USA300 (methicillin resistant), and Burkholderia cepacia, a notoriously antibiotic-resistant organism. Under planktonic, anaerobic conditions, growth of all strains except for P. aeruginosa PAO1 was inhibited by 7.24 mM (512 μg ml−1 NO2 −). B. cepacia was particularly sensitive to low concentrations of A-NO2 − (1.81 mM) under planktonic conditions. In antibiotic-resistant communities known as biofilms, which are reminiscent of end-stage CF airway disease, A-NO2 − killed mucoid P. aeruginosa, S. aureus, and B. cepacia; 1 to 2 logs of cells were killed after a 2-day incubation with a single dose of ∼15 mM A-NO2 −. Animal toxicology and phase I human trials indicate that these bactericidal levels of A-NO2 − can be easily attained by aerosolization. Thus, in summary, we demonstrate that A-NO2 − is very effective at killing these important CF pathogens and could be effective in other infectious settings, particularly under anaerobic conditions where bacterial defenses against the reduction product of A-NO2 −, nitric oxide (NO), are dramatically reduced.

scholarly journals Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms

2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Multiple Infection ◽  
Bacterial Biofilms ◽  
Interspecies Interactions ◽  
Chronic Infections ◽  
Content Type

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.

scholarly journals Cedecea davisae’s Role in a Polymicrobial Lung Infection in a Cystic Fibrosis Patient

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Thayer G. Ismaael ◽  
Eleana M. Zamora ◽  
Faisal A. Khasawneh
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Burkholderia Cepacia ◽  
Airway Disease ◽  
Lung Infection ◽  
Emerging Pathogen ◽  
The Family ◽  
Healthcare Associated ◽  
Airway Colonization

Chronic airway colonization and infection are the hallmark of cystic fibrosis (CF).Staphylococcus aureus, Pseudomonas aeruginosa, andBurkholderia cepaciaare well-documented bacterial culprits in this chronic suppurative airway disease. Advanced molecular diagnostics have uncovered a possible role of a larger group of microorganisms in CF.Cedeceais a member of the family Enterobacteriaceae and is an emerging pathogen. We present a case of a polymicrobial healthcare-associated pneumonia in a CF patient caused byCedecea davisae, among other bacteria.

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 In VitroActivity of Fusidic Acid (CEM-102, Sodium Fusidate) against Staphylococcus aureus Isolates from Cystic Fibrosis Patients and Its Effect on the Activities of Tobramycin and Amikacin against Pseudomonas aeruginosa and Burkholderia cepacia

2011 ◽  
Vol 55 (5) ◽  
pp. 2417-2419 ◽  
Author(s):  
Pamela McGhee ◽  
Catherine Clark ◽  
Kim Credito ◽  
Linda Beachel ◽  
Glenn A. Pankuch ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Protein Binding ◽  
Fusidic Acid ◽  
Burkholderia Cepacia ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACTWe tested the MICs of fusidic acid (CEM-102) plus other agents against 40 methicillin-resistantStaphylococcus aureus(MRSA) isolates from cystic fibrosis patients and the activities of fusidic acid with or without tobramycin or amikacin againstPseudomonas aeruginosa, MRSA, andBurkholderia cepaciaisolates from cystic fibrosis patients in a 24-h time-kill study. Fusidic acid was potent (MICs, 0.125 to 0.5 μg/ml; a single 500-mg dose of fusidic acid at 8 h averaged 8 to 12. 5 μg/ml with 91 to 97% protein binding) against all MRSA strains. No antagonism was observed; synergy occurred for one MRSA strain treated with fusidic acid plus tobramycin.

scholarly journals Inhibition of co-colonizing cystic fibrosis-associated pathogens by Pseudomonas aeruginosa and Burkholderia multivorans

Microbiology ◽  
2014 ◽  
Vol 160 (7) ◽  
pp. 1474-1487 ◽  
Author(s):  
Anne Costello ◽  
F. Jerry Reen ◽  
Fergal O’Gara ◽  
Máire Callaghan ◽  
Siobhán McClean
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Burkholderia Cepacia ◽  
Inflammatory Responses ◽  
Respiratory Infections ◽  
Lung Damage ◽  
Burkholderia Cenocepacia ◽  
Antibiotic Resistant ◽  
Bacterial Dna ◽  
Burkholderia Multivorans

Cystic fibrosis (CF) is a recessive genetic disease characterized by chronic respiratory infections and inflammation causing permanent lung damage. Recurrent infections are caused by Gram-negative antibiotic-resistant bacterial pathogens such as Pseudomonas aeruginosa, Burkholderia cepacia complex (Bcc) and the emerging pathogen genus Pandoraea. In this study, the interactions between co-colonizing CF pathogens were investigated. Both Pandoraea and Bcc elicited potent pro-inflammatory responses that were significantly greater than Ps. aeruginosa. The original aim was to examine whether combinations of pro-inflammatory pathogens would further exacerbate inflammation. In contrast, when these pathogens were colonized in the presence of Ps. aeruginosa the pro-inflammatory response was significantly decreased. Real-time PCR quantification of bacterial DNA from mixed cultures indicated that Ps. aeruginosa significantly inhibited the growth of Burkholderia multivorans, Burkholderia cenocepacia, Pandoraea pulmonicola and Pandoraea apista, which may be a factor in its dominance as a colonizer of CF patients. Ps. aeruginosa cell-free supernatant also suppressed growth of these pathogens, indicating that inhibition was innate rather than a response to the presence of a competitor. Screening of a Ps. aeruginosa mutant library highlighted a role for quorum sensing and pyoverdine biosynthesis genes in the inhibition of B. cenocepacia. Pyoverdine was confirmed to contribute to the inhibition of B. cenocepacia strain J2315. B. multivorans was the only species that could significantly inhibit Ps. aeruginosa growth. B. multivorans also inhibited B. cenocepacia and Pa. apista. In conclusion, both Ps. aeruginosa and B. multivorans are capable of suppressing growth and virulence of co-colonizing CF pathogens.

scholarly journals Metabotypes of Pseudomonas aeruginosa Correlate with Antibiotic Resistance, Virulence and Clinical Outcome in Cystic Fibrosis Chronic Infections

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 63
Author(s):  
Oriane Moyne ◽  
Florence Castelli ◽  
Dominique J. Bicout ◽  
Julien Boccard ◽  
Boubou Camara ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Multiscale Analysis ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Antibiotic Resistant ◽  
Causes Of Mortality ◽  
Lung Infections ◽  
Clinical Measurements

Pseudomonas aeruginosa (P.a) is one of the most critical antibiotic resistant bacteria in the world and is the most prevalent pathogen in cystic fibrosis (CF), causing chronic lung infections that are considered one of the major causes of mortality in CF patients. Although several studies have contributed to understanding P.a within-host adaptive evolution at a genomic level, it is still difficult to establish direct relationships between the observed mutations, expression of clinically relevant phenotypes, and clinical outcomes. Here, we performed a comparative untargeted LC/HRMS-based metabolomics analysis of sequential isolates from chronically infected CF patients to obtain a functional view of P.a adaptation. Metabolic profiles were integrated with expression of bacterial phenotypes and clinical measurements following multiscale analysis methods. Our results highlighted significant associations between P.a “metabotypes”, expression of antibiotic resistance and virulence phenotypes, and frequency of clinical exacerbations, thus identifying promising biomarkers and therapeutic targets for difficult-to-treat P.a infections

scholarly journals Pseudomonas aeruginosa enhances the efficacy of norfloxacin against Staphylococcus aureus biofilms

2020 ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Multiple Infection ◽  
Bacterial Biofilms ◽  
Interspecies Interactions ◽  
Chronic Infections ◽  
Susceptibility Profiles

AbstractThe 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 have been associated with worse lung function. 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 HQNO, siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa to shift S. aureus 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 S. aureus membrane potential, and furthermore, depletion of the S. aureus proton-motive force recapitulates the effect of P. aeruginosa supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus. From these results, we hypothesize that exposure to P. aeruginosa exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus to efflux norfloxacin. Our results illustrate that microbially-derived products can greatly alter the ability of antimicrobial agents to kill bacterial biofilms.ImportancePseudomonas aeruginosa and Staphylococcus aureus are frequently co-isolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and non-healing diabetic foot ulcers. Co-infection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with one 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.

scholarly journals Efficacy of partial purified bacteriocin of Pseudomonas aeruginosa on Methicillin-resistant Staphylococcus aureus biofilm

2019 ◽  
Vol 9 (4-A) ◽  
pp. 438-441
Author(s):  
Arumugam Thangarasu ◽  
Dhanam Selvam ◽  
Sampath Gattu ◽  
Kayalvizhi Nagarajan
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Culture Supernatant ◽  
Chronic Infections ◽  
Antibiotic Resistant ◽  
Methicillin Resistant ◽  
Marked Inhibition ◽  
Ft Ir ◽  
Resistant Microorganism

Biofilms are microbial communities that cause serious chronic infections in the environment by enhancing antimicrobial resistance. Bacteria in the biofilm can be up to a thousand times more resistant to antibiotics than the same bacteria circulating in a planktonic state. The emergence of antibiotic-resistant microorganism has led to the exploration of different therapeutic agents like ribosomally synthesized microorganism peptides referred to as bacteriocins. In this study, bacteriocin producing bacteria Pseudomonas aeruginosa isolated from a soil sample. It was found to be effective against Methicillin-resistant Staphylococcus aureus (MRSA). Furthermore the bacteriocin was partial purified by ammonium sulfate, the precipitate has highly effective against MRSA (400AU/mL). MRSA cells were treated with precipitated culture supernatant of P. aeruginosa TA6 was analyzed by FT-IR. The treated and untreated MRSA showed band variations at 682.59 and 3442.15cm-1 corresponding to the alkyl and amide group respectively. Bacteriocin showed marked inhibition activity against the biofilm of MRSA. About 0.05% and 0.02% attachment of biofilm was observed in the presence of 1X MIC (10 μg/mL) and 2X MIC (20 g/mL) respectively. Our results recommend that bacteriocins that make stable pores on biofilm cells are extremely potent for the treatment of MRSA biofilm infections.

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