Laura J Sherrard1, Bettina Schaible2, Kathryn A Graham2, Stef J McGrath2, Leanne McIlreavey2, Joseph Hatch3, Matthew C Wolfgang3, Marianne S Muhlebach4, Deirdre F Gilpin2, Thamarai Schneiders5, J Stuart Elborn6, Michael M Tunney2. 1. CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK School of Pharmacy, Queen's University Belfast, Belfast, UK l.sherrard@qub.ac.uk. 2. CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK School of Pharmacy, Queen's University Belfast, Belfast, UK. 3. Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 4. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 5. Centre for Infection & Immunity, School of Medicine, Dentistry & Biomedical Science, Queen's University Belfast, Belfast, UK. 6. CF & Airways Microbiology Group, Queen's University Belfast, Belfast, UK Centre for Infection & Immunity, School of Medicine, Dentistry & Biomedical Science, Queen's University Belfast, Belfast, UK.
Abstract
OBJECTIVES: To investigate mechanisms of reduced susceptibility to commonly used antibiotics in Prevotella cultured from patients with cystic fibrosis (CF), patients with invasive infection and healthy control subjects and to determine whether genotype can be used to predict phenotypic resistance. METHODS: The susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within the CfxA-type β-lactamase and expression of efflux pumps. RESULTS: Prevotella isolates positive for a cfxA-type gene had higher MICs of amoxicillin and ceftazidime compared with isolates negative for this gene (P < 0.001). A mutation within the CfxA-type β-lactamase (Y239D) was associated with ceftazidime resistance (P = 0.011). The UK CF isolates were 5.3-fold, 2.7-fold and 5.7-fold more likely to harbour ermF compared with the US CF, UK invasive and UK healthy control isolates, respectively. Higher concentrations of azithromycin (P < 0.001) and clindamycin (P < 0.001) were also required to inhibit the growth of the ermF-positive isolates compared with ermF-negative isolates. Furthermore, tetQ-positive Prevotella isolates had higher MICs of tetracycline (P = 0.001) and doxycycline (P < 0.001) compared with tetQ-negative isolates. Prevotella spp. were also shown, for the first time, to express resistance nodulation division (RND)-type efflux pumps. CONCLUSIONS: This study has demonstrated that Prevotella isolated from various sources harbour a common pool of resistance genes and possess RND-type efflux pumps, which may contribute to tetracycline resistance. The findings indicate that antibiotic resistance is common in Prevotella spp., but the genotypic traits investigated do not reflect phenotypic antibiotic resistance in every instance.
OBJECTIVES: To investigate mechanisms of reduced susceptibility to commonly used antibiotics in Prevotella cultured from patients with cystic fibrosis (CF), patients with invasive infection and healthy control subjects and to determine whether genotype can be used to predict phenotypic resistance. METHODS: The susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within the CfxA-type β-lactamase and expression of efflux pumps. RESULTS: Prevotella isolates positive for a cfxA-type gene had higher MICs of amoxicillin and ceftazidime compared with isolates negative for this gene (P < 0.001). A mutation within the CfxA-type β-lactamase (Y239D) was associated with ceftazidime resistance (P = 0.011). The UK CF isolates were 5.3-fold, 2.7-fold and 5.7-fold more likely to harbour ermF compared with the US CF, UK invasive and UK healthy control isolates, respectively. Higher concentrations of azithromycin (P < 0.001) and clindamycin (P < 0.001) were also required to inhibit the growth of the ermF-positive isolates compared with ermF-negative isolates. Furthermore, tetQ-positive Prevotella isolates had higher MICs of tetracycline (P = 0.001) and doxycycline (P < 0.001) compared with tetQ-negative isolates. Prevotella spp. were also shown, for the first time, to express resistance nodulation division (RND)-type efflux pumps. CONCLUSIONS: This study has demonstrated that Prevotella isolated from various sources harbour a common pool of resistance genes and possess RND-type efflux pumps, which may contribute to tetracycline resistance. The findings indicate that antibiotic resistance is common in Prevotella spp., but the genotypic traits investigated do not reflect phenotypic antibiotic resistance in every instance.
Authors: Farah K Bahrani-Mougeot; Bruce J Paster; Shirley Coleman; Sara Barbuto; Michael T Brennan; Jenene Noll; Thomas Kennedy; Philip C Fox; Peter B Lockhart Journal: J Clin Microbiol Date: 2007-02-14 Impact factor: 5.948
Authors: Marianne S Muhlebach; Joseph E Hatch; Gisli G Einarsson; Stef J McGrath; Deirdre F Gilipin; Gillian Lavelle; Bojana Mirkovic; Michelle A Murray; Paul McNally; Nathan Gotman; Sonia Davis Thomas; Matthew C Wolfgang; Peter H Gilligan; Noel G McElvaney; J Stuart Elborn; Richard C Boucher; Michael M Tunney Journal: Eur Respir J Date: 2018-07-11 Impact factor: 16.671
Authors: Laura J Sherrard; Stef J McGrath; Leanne McIlreavey; Joseph Hatch; Matthew C Wolfgang; Marianne S Muhlebach; Deirdre F Gilpin; J Stuart Elborn; Michael M Tunney Journal: Int J Antimicrob Agents Date: 2015-12-29 Impact factor: 5.283
Authors: Maha R Farhat; Karen R Jacobson; Molly F Franke; Devinder Kaur; Alex Sloutsky; Carole D Mitnick; Megan Murray Journal: J Clin Microbiol Date: 2016-01-13 Impact factor: 5.948
Authors: Cajetan Neubauer; Ajay S Kasi; Nora Grahl; Alex L Sessions; Sebastian H Kopf; Roberta Kato; Deborah A Hogan; Dianne K Newman Journal: J Bacteriol Date: 2018-11-26 Impact factor: 3.490