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. 2012;8(11):e1003043.
doi: 10.1371/journal.ppat.1003043. Epub 2012 Nov 29.

A Trade-Off Between the Fitness Cost of Functional Integrases and Long-Term Stability of Integrons

Free PMC article

A Trade-Off Between the Fitness Cost of Functional Integrases and Long-Term Stability of Integrons

Irina Starikova et al. PLoS Pathog. .
Free PMC article


Horizontal gene transfer (HGT) plays a major role in bacterial microevolution as evident from the rapid emergence and spread of antimicrobial drug resistance. Few studies have however addressed the population dynamics of newly imported genetic elements after HGT. Here, we show that newly acquired class-1 integrons from Salmonella enterica serovar Typhimurium and Acinetobacter baumannii, free of associated transposable elements, strongly reduce host fitness in Acinetobacter baylyi. Insertional inactivation of the integron intI1 restored fitness, demonstrating that the observed fitness costs were due to the presence of an active integrase. The biological cost of harboring class-1 integrons was rapidly reduced during serial transfers due to intI1 frameshift mutations leading to inactivated integrases. We use a mathematical model to explore the conditions where integrons with functional integrases are maintained and conclude that environmental fluctuations and episodic selection is necessary for the maintenance of functional integrases. Taken together, the presented data suggest a trade-off between the ability to capture gene cassettes and long-term stability of integrons and provide an explanation for the frequent observation of inactive integron-integrases in bacterial populations.

Conflict of interest statement

The authors have declared that no competing interests exist.


Figure 1
Figure 1. Results from pair-wise mixed culture competition experiments.
The integron free A. baylyi ADP1 was competed against integron-containing strains with functional or non-functional integrases. Except from the inserted DNA sequences (integrons or nptII sacB) in the selectively neutral ACIAD3309 locus, the strains were isogenic. Results were obtained from at least two independent experiments, and number of parallels ranged from 12–50. Error bars indicate 95% confidence intervals. By definition, a relative fitness of 1.0 indicates no difference in relative fitness. Numbers 1–10 on x-axis describes A. baylyi ADP1 competed against: 1–3; ADP1 with newly acquired integrons, 4–6; ADP1 with newly acquired integrons insertionally inactivated, 7–9; ADP1 with evolved integrons, and 10 insertion-locus control: 1: IVS1 (w = 0.93 [0.91–0.95]; 2; IVS2 (w = 0.98 [0.97–0.99]); 3: IVS3 (w = 0.92 [0.88–0.96]); 4: IVS1 intI1::cat (w = 0.98 [0.97–0.99]); 5: IVS2 intI1::nptII sacB (w = 1.04 [1.00–1.08]); 6: IVS3 intI1::nptII sacB (w = 1.03 [1.00–1.06]); 7: IVS1EV-1 (w = 0.99[0.97–1.01]); 8: IVS1EV-2 (w = 0.98 [0.97–0.99]); 9: IVS1EV-3 (w = 0.99 [0.97–1.01]); 10: IVS4 (w = 1.01 [0.99–1.03]).
Figure 2
Figure 2. 2A) Simulation results depicting the dynamics of integron-containing and - free populations driven by competition and antibiotic selection in serial transfer cultures.
Diamond indicates antibiotic switch. Population I harbors an integron with a functional integrase with one gene cassette encoding resistance to antibiotic A (dark blue line). Population I2 has acquired a second gene cassette and encodes resistance to both antibiotics A and B (black line). Following frameshift and nonsense mutations in the functional integrase, populations I1 and I2 form M1 (light blue line) and M2 (grey line), respectively. Population P (green line) is the integron-free wild type. The results shown are the median values of 100 realizations until the I2 population falls below 1 CFU per ml. 2B) Persistence of integrons with functional integrases: The connected crosshairs presented in figure 2B shows the proportion of realizations where the functional integrase (in population I2) is still present after 50 additional transfers following different time intervals between shifts from antibiotic A to B.

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This project was funded by the University of Tromsø and grants from the Norwegian Research Council 204263 and Tromsø Forskningsstiftelse awarded PJJ. ØS was supported by a grant from the Northern Norway Regional Health Authority. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.