title: Production of extended-spectrum β-lactamases and the potential indirect pathogenic role of Prevotella isolates from the cystic fibrosis respiratory microbiota.
abstract: Extended-spectrum β-lactamase (ESBL) production and the prevalence of the β-lactamase-encoding gene blaTEM were determined in Prevotella isolates (n=50) cultured from the respiratory tract of adults and young people with cystic fibrosis (CF). Time-kill studies were used to investigate the concept of passive antibiotic resistance and to ascertain whether a β-lactamase-positive Prevotella isolate can protect a recognised CF pathogen from the action of ceftazidime in vitro. The results indicated that approximately three-quarters (38/50; 76%) of Prevotella isolates produced ESBLs. Isolates positive for ESBL production had higher minimum inhibitory concentrations (MICs) of β-lactam antibiotics compared with isolates negative for production of ESBLs (P<0.001). The blaTEM gene was detected more frequently in CF Prevotella isolates from paediatric patients compared with isolates from adults (P=0.002), with sequence analysis demonstrating that 21/22 (95%) partial blaTEM genes detected were identical to blaTEM-116. Furthermore, a β-lactamase-positive Prevotella isolate protected Pseudomonas aeruginosa from the antimicrobial effects of ceftazidime (P=0.03). Prevotella isolated from the CF respiratory microbiota produce ESBLs and may influence the pathogenesis of chronic lung infection via indirect methods, including shielding recognised pathogens from the action of ceftazidime.
authors.affiliation: CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK; School of Pharmacy, Queen's University Belfast, Belfast, UK. Electronic address: lsherrard03@qub.ac.uk.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Sherrard
authors.affiliation: CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK; School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Stef J
authors.initials: SJ
authors.lastname: McGrath
authors.affiliation: CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK; School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Leanne
authors.initials: L
authors.lastname: McIlreavey
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hatch
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wolfgang
authors.affiliation: Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Muhlebach
authors.affiliation: CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK; School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Deirdre F
authors.initials: DF
authors.lastname: Gilpin
authors.affiliation: CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK; Centre for Infection & Immunity, School of Medicine, Dentistry & Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
authors.affiliation: CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK; School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Tunney
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008875:Middle Aged; D018720:Prevotella / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D012141:Respiratory Tract Infections / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D055815:Young Adult; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D002442:Ceftazidime; D001618:beta-Lactamases
keywords: Anaerobes; Antibiotic resistance; Cystic fibrosis; β-Lactams