scholarly journals Stenotrophomonas maltophiliaDifferential Gene Expression in Synthetic Cystic Fibrosis Sputum Reveals Shared and Cystic Fibrosis Strain-Specific Responses to the Sputum Environment

2019 ◽  
Vol 201 (15) ◽  
Author(s):  
Graham G. Willsey ◽  
Korin Eckstrom ◽  
Annette E. LaBauve ◽  
Lauren A. Hinkel ◽  
Kristin Schutz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Stress Responses ◽  
Metabolic Pathways ◽  
Stenotrophomonas Maltophilia ◽  
Acute Infection ◽  
Survival Strategies ◽  
Transcriptional Responses ◽  
Content Type ◽  
Insight Into

ABSTRACTStenotrophomonas maltophiliais a Gram-negative opportunistic pathogen that can infect the lungs of people with cystic fibrosis (CF). The highly viscous mucus in the CF lung, expectorated as sputum, serves as the primary nutrient source for microbes colonizing this site and induces virulence-associated phenotypes and gene expression in several CF pathogens. Here, we characterized the transcriptional responses of threeS. maltophiliastrains during exposure to synthetic CF sputum medium (SCFM2) to gain insight into how this organism interacts with the host in the CF lung. These efforts led to the identification of 881 transcripts differentially expressed by all three strains, many of which reflect the metabolic pathways used byS. maltophiliain sputum, as well as altered stress responses. The latter correlated with increased resistance to peroxide exposure after pregrowth in SCFM2 for two of the strains. We also compared the SCFM2 transcriptomes of twoS. maltophiliaCF isolates to that of the acute infection strain,S. maltophiliaK279a, allowing us to identify CF isolate-specific signatures in differential gene expression. The expression of genes from the accessory genomes was also differentially altered in response to SCFM2. Finally, a number of biofilm-associated genes were differentially induced in SCFM2, particularly in K279a, which corresponded to increased aggregation and biofilm formation in this strain relative to both CF strains. Collectively, this work details the response ofS. maltophiliato an environment that mimics important aspects of the CF lung, identifying potential survival strategies and metabolic pathways used byS. maltophiliaduring infections.IMPORTANCEStenotrophomonas maltophiliais an important infecting bacterium in the airways of people with cystic fibrosis (CF). However, compared to the other CF pathogens,S. maltophiliahas been relatively understudied. The significance of our research is to provide insight into the global transcriptomic changes ofS. maltophiliain response to a medium that was designed to mimic important aspects of the CF lung. This study elucidates the overall metabolic changes that occur whenS. maltophiliaencounters the CF lung and generates a road map of candidate genes to test usingin vitroandin vivomodels of CF.

scholarly journals Chitin-Induced Gene Expression in Secondary Metabolic Pathways of Streptomyces coelicolor A3(2) Grown in Soil

2012 ◽  
Vol 79 (2) ◽  
pp. 707-713 ◽  
Author(s):  
Behnam Nazari ◽  
Michihiko Kobayashi ◽  
Akihiro Saito ◽  
Azam Hassaninasab ◽  
Kiyotaka Miyashita ◽  
...  
Keyword(s):  
Gene Expression ◽  
Secondary Metabolism ◽  
Stress Responses ◽  
Metabolic Pathways ◽  
Streptomyces Coelicolor ◽  
Regulation Of Gene Expression ◽  
Content Type ◽  
Metabolic Genes ◽  
Expression Of Genes ◽  
Microarray Analyses

ABSTRACTMicroarray analyses revealed that the expression of genes for secondary metabolism together with that of primary metabolic genes was induced by chitin in autoclaved soil cultures ofStreptomyces coelicolorA3(2). The data also indicated that DasR was involved in the regulation of gene expression for chitin catabolism, secondary metabolism, and stress responses.

scholarly journals Stenotrophomonas maltophilia phenotypic and genotypic features through 4-year cystic fibrosis lung colonization

2020 ◽  
Author(s):  
Eliana Alcaraz ◽  
Daniela Centrón ◽  
Gabriela Camicia ◽  
María Paula Quiroga ◽  
José Di Conza ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Adult Patient ◽  
Virulence Factors ◽  
Stenotrophomonas Maltophilia ◽  
Type Species ◽  
Mutation Frequency ◽  
Content Type ◽  
Link Type ◽  
Clonal Relatedness ◽  
Over Time

Introduction. Stenotrophomonas maltophilia has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Hypothesis. Sequential isolates of S. maltophilia from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. Aim. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential S. maltophilia isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. Methodology. The antibiotic resistance of 11 S. maltophilia isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC–RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Results. Seven S. maltophilia isolates were resistant to trimethoprim–sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. XbaI PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC–RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified stmPr1 and stmPr2 genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. Conclusion. The present study shows the long-time persistence of two related S. maltophilia clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.

scholarly journals Cystic Fibrosis-AssociatedStenotrophomonas maltophiliaStrain-Specific Adaptations and Responses to pH

2019 ◽  
Vol 201 (7) ◽  
Author(s):  
Tara Gallagher ◽  
Joann Phan ◽  
Andrew Oliver ◽  
Alexander B. Chase ◽  
Whitney E. England ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Stenotrophomonas Maltophilia ◽  
Opportunistic Infections ◽  
Expression Profiles ◽  
Bacterial Colonization ◽  
Low Ph ◽  
Lung Damage ◽  
Ph Gradients ◽  
Content Type ◽  
The Impact

ABSTRACTThe airway fluids of cystic fibrosis (CF) patients contain local pH gradients and are more acidic than those of healthy individuals. pH is a critical factor that is often overlooked in studies seeking to recapitulate the infection microenvironment. We sought to determine the impact of pH on the physiology of a ubiqituous yet understudied microbe,Stenotrophomonas maltophilia. Phylogenomics was first used to reconstruct evolutionary relationships between 74 strains ofS. maltophilia(59 from CF patients). Neither the core genome (2,158 genes) nor the accessory genome (11,978 genes) distinguish the CF and non-CF isolates; however, strains from similar isolation sources grouped into the same subclades. We grew two human and six CFS. maltophiliaisolates from different subclades at a range of pH values and observed impaired growth and altered antibiotic tolerances at pH 5. Transcriptomes revealed increased expression of both antibiotic resistance and DNA repair genes in acidic conditions. Although the gene expression profiles ofS. maltophiliain lab cultures and CF sputum were distinct, we found that the same genes associated with low pH were also expressed during infection, and the higher pH cultures were more similar to sputum metatranscriptomes. Our findings suggest thatS. maltophiliais not well adapted to acidity and may cope with low pH by expressing stress response genes and colonizing less acidic microenvironments. As a whole, our study underlines the impact of microenvironments on bacterial colonization and adaptation in CF infections.IMPORTANCEUnderstanding bacterial responses to physiological conditions is an important priority for combating opportunistic infections. The majority of CF patients succumb to inflammation and necrosis in the airways, arising from chronic infection due to ineffective mucociliary clearance. Steep pH gradients characterize the CF airways but are not often incorporated in standard microbiology culture conditions.Stenotrophomonas maltophiliais a prevalent CF opportunistic pathogen also found in many disparate environments, yet this bacterium’s contribution to CF lung damage and its response to changing environmental factors remain largely understudied. Here, we show that pH impacts the physiology and antibiotic susceptibility ofS. maltophilia, with implications for the development of relevantin vitromodels and assessment of antibiotic sensitivity.

scholarly journals Contextual Flexibility in Pseudomonas aeruginosa Central Carbon Metabolism during Growth in Single Carbon Sources

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Stephen K. Dolan ◽  
Michael Kohlstedt ◽  
Stephen Trigg ◽  
Pedro Vallejo Ramirez ◽  
Clemens F. Kaminski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Metabolic Flux ◽  
Antimicrobial Agents ◽  
Carbon Sources ◽  
Aerobic Denitrification ◽  
Human Pathogen ◽  
Content Type ◽  
Opportunistic Human Pathogen

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile of P. aeruginosa appears to converge toward a common metabolic program as the organism adapts to the CF airway environment. However, we still have only a limited understanding of how these transcriptional changes impact metabolic flux at the systems level. To address this, we analyzed the transcriptome, proteome, and fluxome of P. aeruginosa grown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of an airway surfactant, phosphatidylcholine, which is known to be a major carbon source for P. aeruginosa in CF airways. We show that the fluxes of carbon throughout central metabolism are radically different among carbon sources. For example, the newly recognized “EDEMP cycle” (which incorporates elements of the Entner-Doudoroff [ED] pathway, the Embden-Meyerhof-Parnas [EMP] pathway, and the pentose phosphate [PP] pathway) plays an important role in supplying NADPH during growth on glycerol. In contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the reaction catalyzed by isocitrate dehydrogenase(s). Perhaps more importantly, our proteomic and transcriptomic analyses revealed a global remodeling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity of P. aeruginosa; that plasticity allows the organism to seamlessly segue between different carbon sources, maximizing the energetic yield from each. IMPORTANCE Pseudomonas aeruginosa is an opportunistic human pathogen that is well known for causing infections in the airways of people with cystic fibrosis. Although it is clear that P. aeruginosa is metabolically well adapted to life in the CF lung, little is currently known about how the organism metabolizes the nutrients available in the airways. In this work, we used a combination of gene expression and isotope tracer (“fluxomic”) analyses to find out exactly where the input carbon goes during growth on two CF-relevant carbon sources, acetate and glycerol (derived from the breakdown of lung surfactant). We found that carbon is routed (“fluxed”) through very different pathways during growth on these substrates and that this is accompanied by an unexpected remodeling of the cell’s electron transfer pathways. Having access to this “blueprint” is important because the metabolism of P. aeruginosa is increasingly being recognized as a target for the development of much-needed antimicrobial agents.

scholarly journals Short- and Long-Term Transcriptomic Responses of Escherichia coli to Biocides: a Systems Analysis

2020 ◽  
Vol 86 (14) ◽  
Author(s):  
Beatriz Merchel Piovesan Pereira ◽  
Xiaokang Wang ◽  
Ilias Tagkopoulos
Keyword(s):  
Escherichia Coli ◽  
Stress Response ◽  
Stress Responses ◽  
Zinc Homeostasis ◽  
Cross Resistance ◽  
Transcriptional Responses ◽  
Systematic Analysis ◽  
Content Type ◽  
Short Term Exposure

ABSTRACT The mechanisms of the bacterial response to biocides are poorly understood, despite their broad application. To identify the genetic basis and pathways implicated in the biocide stress response, we exposed Escherichia coli populations to 10 ubiquitous biocides. By comparing the transcriptional responses between a short-term exposure (30 min) and a long-term exposure (8 to 12 h) to biocide stress, we established the common gene and pathway clusters that are implicated in general and biocide-specific stress responses. Our analysis revealed a temporal choreography, starting from the upregulation of chaperones to the subsequent repression of motility and chemotaxis pathways and the induction of an anaerobic pool of enzymes and biofilm regulators. A systematic analysis of the transcriptional data identified a zur-regulated gene cluster to be highly active in the stress response against sodium hypochlorite and peracetic acid, presenting a link between the biocide stress response and zinc homeostasis. Susceptibility assays with knockout mutants further validated our findings and provide clear targets for downstream investigation of the implicated mechanisms of action. IMPORTANCE Antiseptics and disinfectant products are of great importance to control and eliminate pathogens, especially in settings such as hospitals and the food industry. Such products are widely distributed and frequently poorly regulated. Occasional outbreaks have been associated with microbes resistant to such compounds, and researchers have indicated potential cross-resistance with antibiotics. Despite that, there are many gaps in knowledge about the bacterial stress response and the mechanisms of microbial resistance to antiseptics and disinfectants. We investigated the stress response of the bacterium Escherichia coli to 10 common disinfectant and antiseptic chemicals to shed light on the potential mechanisms of tolerance to such compounds.

scholarly journals Identification of Dephospho-Coenzyme A (Dephospho-CoA) Kinase in Thermococcus kodakarensis and Elucidation of the Entire CoA Biosynthesis Pathway in Archaea

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Takahiro Shimosaka ◽  
Kira S. Makarova ◽  
Eugene V. Koonin ◽  
Haruyuki Atomi
Keyword(s):  
Metabolic Pathways ◽  
Coenzyme A ◽  
Protein A ◽  
Biosynthesis Pathway ◽  
Content Type ◽  
Hyperthermophilic Archaeon ◽  
Thermococcus Kodakarensis ◽  
Uncharacterized Gene ◽  
Wide Range ◽  
Insight Into

ABSTRACT Dephospho-coenzyme A (dephospho-CoA) kinase (DPCK) catalyzes the ATP-dependent phosphorylation of dephospho-CoA, the final step in coenzyme A (CoA) biosynthesis. DPCK has been identified and characterized in bacteria and eukaryotes but not in archaea. The hyperthermophilic archaeon Thermococcus kodakarensis encodes two homologs of bacterial DPCK and the DPCK domain of eukaryotic CoA synthase, TK1334 and TK2192. We purified the recombinant TK1334 and TK2192 proteins and found that they lacked DPCK activity. Bioinformatic analyses showed that, in several archaea, the uncharacterized gene from arCOG04076 protein is fused with the gene for phosphopantetheine adenylyltransferase (PPAT), which catalyzes the reaction upstream of the DPCK reaction in CoA biosynthesis. This observation suggested that members of arCOG04076, both fused to PPAT and standalone, could be the missing archaeal DPCKs. We purified the recombinant TK1697 protein, a standalone member of arCOG04076 from T. kodakarensis, and demonstrated its GTP-dependent DPCK activity. Disruption of the TK1697 resulted in CoA auxotrophy, indicating that TK1697 encodes a DPCK that contributes to CoA biosynthesis in T. kodakarensis. TK1697 homologs are widely distributed in archaea, suggesting that the arCOG04076 protein represents a novel family of DPCK that is not homologous to bacterial and eukaryotic DPCKs but is distantly related to bacterial and eukaryotic thiamine pyrophosphokinases. We also constructed and characterized gene disruption strains of TK0517 and TK2128, homologs of bifunctional phosphopantothenoylcysteine synthetase-phosphopantothenoylcysteine decarboxylase and PPAT, respectively. Both strains displayed CoA auxotrophy, indicating their contribution to CoA biosynthesis. Taken together with previous studies, the results experimentally validate the entire CoA biosynthesis pathway in T. kodakarensis. IMPORTANCE CoA is utilized in a wide range of metabolic pathways, and its biosynthesis is essential for all life. Pathways for CoA biosynthesis in bacteria and eukaryotes have been established. In archaea, however, the enzyme that catalyzes the final step in CoA biosynthesis, dephospho-CoA kinase (DPCK), had not been identified. In the present study, bioinformatic analyses identified a candidate for the DPCK in archaea, which was biochemically and genetically confirmed in the hyperthermophilic archaeon Thermococcus kodakarensis. Genetic analyses on genes presumed to encode bifunctional phosphopantothenoylcysteine synthetase-phosphopantothenoylcysteine decarboxylase and phosphopantetheine adenylyltransferase confirmed their involvement in CoA biosynthesis. Taken together with previous studies, the results reveal the entire pathway for CoA biosynthesis in a single archaeon and provide insight into the different mechanisms of CoA biosynthesis and their distribution in nature.

scholarly journals Physiological and Transcriptional Responses of Different Industrial Microbes at Near-Zero Specific Growth Rates

2015 ◽  
Vol 81 (17) ◽  
pp. 5662-5670 ◽  
Author(s):  
Onur Ercan ◽  
Markus M. M. Bisschops ◽  
Wout Overkamp ◽  
Thomas R. Jørgensen ◽  
Arthur F. Ram ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Rates ◽  
Microbial Growth ◽  
Current Knowledge ◽  
Product Formation ◽  
Natural Ecosystems ◽  
Transcriptional Responses ◽  
Content Type ◽  
Growth Physiology ◽  
Zero Growth

ABSTRACTThe current knowledge of the physiology and gene expression of industrially relevant microorganisms is largely based on laboratory studies under conditions of rapid growth and high metabolic activity. However, in natural ecosystems and industrial processes, microbes frequently encounter severe calorie restriction. As a consequence, microbial growth rates in such settings can be extremely slow and even approach zero. Furthermore, uncoupling microbial growth from product formation, while cellular integrity and activity are maintained, offers perspectives that are economically highly interesting. Retentostat cultures have been employed to investigate microbial physiology at (near-)zero growth rates. This minireview compares information from recent physiological and gene expression studies on retentostat cultures of the industrially relevant microorganismsLactobacillus plantarum,Lactococcus lactis,Bacillus subtilis,Saccharomyces cerevisiae, andAspergillus niger. Shared responses of these organisms to (near-)zero growth rates include increased stress tolerance and a downregulation of genes involved in protein synthesis. Other adaptations, such as changes in morphology and (secondary) metabolite production, were species specific. This comparison underlines the industrial and scientific significance of further research on microbial (near-)zero growth physiology.

scholarly journals S-Inosyl-l-Homocysteine Hydrolase, a Novel Enzyme Involved inS-Adenosyl-l-Methionine Recycling

2015 ◽  
Vol 197 (14) ◽  
pp. 2284-2291 ◽  
Author(s):  
Danielle Miller ◽  
Huimin Xu ◽  
Robert H. White
Keyword(s):  
Metabolic Pathways ◽  
Methanogenic Archaea ◽  
Metabolite Identification ◽  
Strictly Anaerobic ◽  
Methanocaldococcus Jannaschii ◽  
Content Type ◽  
Sequence Identity ◽  
Feedback Inhibitor ◽  
Recycling Pathway ◽  
Insight Into

ABSTRACTS-Adenosyl-l-homocysteine, the product ofS-adenosyl-l-methionine (SAM) methyltransferases, is known to be a strong feedback inhibitor of these enzymes. A hydrolase specific forS-adenosyl-l-homocysteine producesl-homocysteine, which is remethylated to methionine and can be used to regenerate SAM. Here, we show that the annotatedS-adenosyl-l-homocysteine hydrolase inMethanocaldococcus jannaschiiis specific for the hydrolysis and synthesis ofS-inosyl-l-homocysteine, notS-adenosyl-l-homocysteine. This is the first report of an enzyme specific forS-inosyl-l-homocysteine. As withS-adenosyl-l-homocysteine hydrolase, which shares greater than 45% sequence identity with theM. jannaschiihomologue, theM. jannaschiienzyme was found to copurify with bound NAD+and hasKmvalues of 0.64 ± 0.4 mM, 0.0054 ± 0.006 mM, and 0.22 ± 0.11 mM for inosine,l-homocysteine, andS-inosyl-l-homocysteine, respectively. No enzymatic activity was detected withS-adenosyl-l-homocysteine as the substrate in either the synthesis or hydrolysis direction. These results prompted us to redesignate theM. jannaschiienzyme anS-inosyl-l-homocysteine hydrolase (SIHH). Identification of SIHH demonstrates a modified pathway in this methanogen for the regeneration of SAM fromS-adenosyl-l-homocysteine that uses the deamination ofS-adenosyl-l-homocysteine to formS-inosyl-l-homocysteine.IMPORTANCEIn strictly anaerobic methanogenic archaea, such asMethanocaldococcus jannaschii, canonical metabolic pathways are often not present, and instead, unique pathways that are deeply rooted on the phylogenetic tree are utilized by the organisms. Here, we discuss the recycling pathway forS-adenosyl-l-homocysteine, produced fromS-adenosyl-l-methionine (SAM)-dependent methylation reactions, which uses a hydrolase specific forS-inosyl-l-homocysteine, an uncommon metabolite. Identification of the pathways and the enzymes involved in the unique pathways in the methanogens will provide insight into the biochemical reactions that were occurring when life originated.

scholarly journals Metatranscriptome Analysis for Insight into Whole-Ecosystem Gene Expression during Spontaneous Wheat and Spelt Sourdough Fermentations

2010 ◽  
Vol 77 (2) ◽  
pp. 618-626 ◽  
Author(s):  
Stefan Weckx ◽  
Joke Allemeersch ◽  
Roel Van der Meulen ◽  
Gino Vrancken ◽  
Geert Huys ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Fermented Foods ◽  
Gene Microarray ◽  
Organoleptic Properties ◽  
Redox Equilibrium ◽  
Flavor Compound ◽  
Approaches To Study ◽  
Microarray Analyses ◽  
Insight Into

ABSTRACTLactic acid bacteria (LAB) are of industrial importance in the production of fermented foods, including sourdough-derived products. Despite their limited metabolic capacity, LAB contribute considerably to important characteristics of fermented foods, such as extended shelf-life, microbial safety, improved texture, and enhanced organoleptic properties. Triggered by the considerable amount of LAB genomic information that became available during the last decade, transcriptome and, by extension, metatranscriptome studies have become one of the most appropriate research approaches to study whole-ecosystem gene expression in more detail. In this study, microarray analyses were performed using RNA sampled during four 10-day spontaneous sourdough fermentations carried out in the laboratory with an in-house-developed LAB functional gene microarray. For data analysis, a new algorithm was developed to calculate a net expression profile for each of the represented genes, allowing use of the microarray analysis beyond the species level. In addition, metabolite target analyses were performed on the sourdough samples to relate gene expression with metabolite production. The results revealed the activation of different key metabolic pathways, the ability to use carbohydrates other than glucose (e.g., starch and maltose), and the conversion of amino acids as a contribution to redox equilibrium and flavor compound generation in LAB during sourdough fermentation.

scholarly journals Biofilm Compared to Conventional Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from Cystic Fibrosis Patients

2013 ◽  
Vol 57 (3) ◽  
pp. 1546-1548 ◽  
Author(s):  
Kitty Wu ◽  
Yvonne C. W. Yau ◽  
Larissa Matukas ◽  
Valerie Waters
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Susceptibility ◽  
Stenotrophomonas Maltophilia ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Resistant Organism ◽  
High Dose ◽  
Content Type

ABSTRACTStenotrophomonas maltophiliais a multidrug-resistant organism increasingly isolated from the lungs of cystic fibrosis (CF) patients. One hundred twenty-fiveS. maltophiliaisolates from 85 CF patients underwent planktonic and biofilm susceptibility testing against 9 different antibiotics, alone and in double antibiotic combinations. WhenS. maltophiliaisolates were grown as a biofilm, 4 of the 10 most effective antibiotic combinations included high-dose levofloxacin and 7 of the 10 combinations included colistin at doses achievable by aerosolization.

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