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In JoVE (1)
Other Publications (4)
Articles by Craig Winstanley in JoVE
JoVE Immunology and Infection
Use of Artificial Sputum Medium to Test Antibiotic Efficacy Against Pseudomonas aeruginosa in Conditions More Relevant to the Cystic Fibrosis Lung
1Institute of Infection and Global Health, University of Liverpool, 2NIHR Biomedical Research Centre in Microbial Disease, University of Liverpool
Current diagnostic antimicrobial susceptibility testing relies on the planktonic growth of isolates in nutrient rich, aerobic conditions. Here, we employ an alternative artificial sputum medium to study antimicrobial susceptibility of Pseudomonas aeruginosa biofilms under both aerobic and microaerophilic conditions more representative of the cystic fibrosis lung.
Other articles by Craig Winstanley on PubMed
Characterization of Epithelial IL-8 Response to Inflammatory Bowel Disease Mucosal E. Coli and Its Inhibition by Mesalamine
Mucosally adherent E. coli are found in inflammatory bowel disease (IBD) and colon cancer. They promote release of the proinflammatory cytokine interleukin-8 (IL-8). We explored mechanisms for this release and its inhibition by drugs.
In Vivo Growth of Pseudomonas Aeruginosa Strains PAO1 and PA14 and the Hypervirulent Strain LESB58 in a Rat Model of Chronic Lung Infection
Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity and mortality in cystic fibrosis (CF) patients. The P. aeruginosa strains PAO1 and PA14 were compared with the Liverpool epidemic strain LESB58 to assess in vivo growth, infection kinetics, and bacterial persistence and localization within tissues in a rat model of chronic lung infection. The three P. aeruginosa strains demonstrated similar growth curves in vivo but differences in tissue distribution. The LESB58 strain persisted in the bronchial lumen, while the PAO1 and PA14 strains were found localized in the alveolar regions and grew as macrocolonies after day 7 postinfection. Bacterial strains were compared for swimming and twitching motility and for the production of biofilm. The P. aeruginosa LESB58 strain produced more biofilm than PAO1 and PA14. Competitive index (CI) analysis of PAO1, PA14, and LESB58 in vivo indicated CI values of 0.002, 0.0002, and 0.14 between PAO1-PA14, PAO1-LESB58, and LESB58-PA14, respectively. CI analysis comparing the in vivo growth of the PAO1 DeltaPA5441 mutant and four PA14 surface attachment-defective (sad) mutants gave CI values 10 to 1,000 times lower in competitions with their respective wild-type strains PAO1 and PA14. P. aeruginosa strains studied in the rat model of chronic lung infection demonstrated similar in vivo growth but differences in virulence as shown with a competitive in vivo assay. These differences were further confirmed with biofilm and motility in vitro assays, where strain LESB58 produced more biofilm but had less capacity for motility than PAO1 and PA14.
A Subtype of a Pseudomonas Aeruginosa Cystic Fibrosis Epidemic Strain Exhibits Enhanced Virulence in a Murine Model of Acute Respiratory Infection
The Liverpool epidemic strain (LES) of Pseudomonas aeruginosa is a particularly successful cystic fibrosis (CF) pathogen associated with transmissibility, increased patient morbidity, and, unusually, infection of the non-CF parents of a patient with CF.
Novel Therapeutic Strategies to Counter Pseudomonas Aeruginosa Infections
Pseudomonas aeruginosa is a highly successful opportunistic pathogen that displays intrinsic multidrug resistance and has a tremendous capacity to acquire further resistance mechanisms. During chronic infection, the bacterium can form a protective biofilm therefore reducing the efficacy of existing antibiotics. P. aeruginosa also harbors an impressive range of virulence factors, many of which are controlled by the quorum-sensing system. Several novel therapeutics are under investigation such as those directed against biofilm formation and quorum-sensing systems along with bacteriophages and immunotherapies. Recent advances in next-generation sequencing and comparative genomics have opened the door to a new wave of smart drug design that could revolutionize P. aeruginosa treatment options.
