Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype
Fluoroquinolone (FQ) resistance is highly prevalent among clinical strains of Pseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing the exoU gene of the type III secretion system are more likely to be FQ-resistant than strains contain...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-10-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01591/full |
| _version_ | 1818304283622244352 |
|---|---|
| author | Melissa Agnello Steven E. Finkel Annie Wong-Beringer |
| author_facet | Melissa Agnello Steven E. Finkel Annie Wong-Beringer |
| author_sort | Melissa Agnello |
| collection | DOAJ |
| description | Fluoroquinolone (FQ) resistance is highly prevalent among clinical strains of Pseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing the exoU gene of the type III secretion system are more likely to be FQ-resistant than strains containing the exoS gene, as well as more likely to acquire resistance-conferring mutations in gyrA/B and parC/E. We hypothesize that FQ-resistance imposes a lower fitness cost on exoU compared to exoS strains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation in parC from 3 exoU and 3 exoS clinical isolates and tested fitness in vitro using head-to-head competition assays. The mutation differentially affected fitness in the exoU and exoS strains tested. While the addition of the parC mutation dramatically increased fitness in one of the exoU strains leaving the other two unaffected, all three exoS strains displayed a general decrease in fitness. In addition, we found that exoU strains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to the exoS strains. These results may provide a biological explanation for the observed predominance of the virulent exoU genotype in FQ-resistant clinical subpopulations and represent the first investigation into potential differences in fitness costs of FQ-resistance that are linked to the virulence genotype of P. aeruginosa. Understanding the fitness costs of antibiotic resistance and possibilities of compensation for these costs is essential for the rational development of strategies to combat the problem of antibiotic resistance. |
| first_indexed | 2024-12-13T06:08:14Z |
| format | Article |
| id | doaj.art-535afa55aa07420283ef9701b3345e35 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T06:08:14Z |
| publishDate | 2016-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-535afa55aa07420283ef9701b3345e352022-12-21T23:57:10ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-10-01710.3389/fmicb.2016.01591206243Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion GenotypeMelissa Agnello0Steven E. Finkel1Annie Wong-Beringer2University of Southern CaliforniaUniversity of Southern CaliforniaUniversity of Southern CaliforniaFluoroquinolone (FQ) resistance is highly prevalent among clinical strains of Pseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing the exoU gene of the type III secretion system are more likely to be FQ-resistant than strains containing the exoS gene, as well as more likely to acquire resistance-conferring mutations in gyrA/B and parC/E. We hypothesize that FQ-resistance imposes a lower fitness cost on exoU compared to exoS strains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation in parC from 3 exoU and 3 exoS clinical isolates and tested fitness in vitro using head-to-head competition assays. The mutation differentially affected fitness in the exoU and exoS strains tested. While the addition of the parC mutation dramatically increased fitness in one of the exoU strains leaving the other two unaffected, all three exoS strains displayed a general decrease in fitness. In addition, we found that exoU strains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to the exoS strains. These results may provide a biological explanation for the observed predominance of the virulent exoU genotype in FQ-resistant clinical subpopulations and represent the first investigation into potential differences in fitness costs of FQ-resistance that are linked to the virulence genotype of P. aeruginosa. Understanding the fitness costs of antibiotic resistance and possibilities of compensation for these costs is essential for the rational development of strategies to combat the problem of antibiotic resistance.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01591/fullPseudomonas aeruginosaVirulencefitnessType III SecretionFluoroquinolone resistance |
| spellingShingle | Melissa Agnello Steven E. Finkel Annie Wong-Beringer Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype Frontiers in Microbiology Pseudomonas aeruginosa Virulence fitness Type III Secretion Fluoroquinolone resistance |
| title | Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype |
| title_full | Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype |
| title_fullStr | Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype |
| title_full_unstemmed | Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype |
| title_short | Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype |
| title_sort | fitness cost of fluoroquinolone resistance in clinical isolates of pseudomonas aeruginosa differs by type iii secretion genotype |
| topic | Pseudomonas aeruginosa Virulence fitness Type III Secretion Fluoroquinolone resistance |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01591/full |
| work_keys_str_mv | AT melissaagnello fitnesscostoffluoroquinoloneresistanceinclinicalisolatesofpseudomonasaeruginosadiffersbytypeiiisecretiongenotype AT stevenefinkel fitnesscostoffluoroquinoloneresistanceinclinicalisolatesofpseudomonasaeruginosadiffersbytypeiiisecretiongenotype AT anniewongberinger fitnesscostoffluoroquinoloneresistanceinclinicalisolatesofpseudomonasaeruginosadiffersbytypeiiisecretiongenotype |