Small-Plasmid-Mediated Antibiotic Resistance Is Enhanced by Increases in Plasmid Copy Number and Bacterial Fitness
Artículo de investigación publicado en Antimicrobial Agents and Chemotherapy
1 de junio de 2015
Plasmids play a key role in the horizontal spread of antibiotic resistance determinants among bacterial pathogens. When an antibiotic-resistance plasmid arrives to a new bacterial host it produces a fitness cost, causing a competitive disadvantage for the plasmid-bearing bacterium in the absence of antibiotics. On the other hand, in the presence of antibiotics the plasmid promotes the survival of the clone. The adaptations experienced by plasmid and bacteria in the presence of antibiotics during the first generations of coexistence will be crucial for the progress of the infection and the maintenance of plasmid-mediated resistance once the treatment is over. Here we developed a model system using the human pathogen Haemophilus influenzae carrying the small plasmid pB1000 conferring resistance to β-lactam antibiotics to investigate host and plasmid adaptations in the course of a simulated ampicillin therapy. Our results proved that plasmid-bearing clones compensated the fitness disadvantage during the first 100 generations of plasmid-host adaptation. In addition, ampicillin treatment was associated with an increase in pB1000 copy number. The augmentation in both bacterial fitness and plasmid copy number gave rise to H. influenzae populations with higher ampicillin resistance level. In conclusion, we show here that the modulations in bacterial fitness and plasmid copy number help a plasmid-bearing bacterium to adapt during antibiotic therapy, promoting both the survival of the host and the spread of the plasmid
San Millan A., Santos-Lopez A., Ortega-Huedo R., Bernabe-Balas C., Kennedy SP. y Gonzalez-Zorn B..
Servicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM). | |
Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM). | |
Institut National de la Recherche Agronomique (INRA). | |