Predicting bacterial fitness cost associated with drug resistance.
OBJECTIVE
It has been proposed that antimicrobial resistance could be associated with a fitness cost in bacteria, which is often determined by competition experiments between isogenic strains (wild-type and mutant). However, this conventional approach is time consuming and labour intensive. An alternative method was developed to assess the fitness cost in drug-resistant bacteria.


METHODS
Time-growth studies were performed with approximately 1 × 10(5) cfu/mL of Acinetobacter baumannii or Pseudomonas aeruginosa at baseline. Serial samples were obtained to quantify the bacterial burden over 24 h. The growth rates (K(g)) of isogenic strains (antibiotic susceptible and resistant) were determined individually and used to predict their relative abundance in a co-culture over an extended period of time. The predicted difference between the two strains was subsequently validated by in vitro growth competition experiments.


RESULTS
The growth rates of A. baumannii were not significantly different in different strengths of growth medium. The difference in bacterial burden observed in competition studies was in general agreement with the predicted difference based on K(g) values, suggesting good predicting ability of the mathematical model.


CONCLUSIONS
The proposed mathematical model was found to be reasonable in characterizing bacterial growth and predicting the fitness cost of resistance. This simple method appears robust in the assessment of fitness cost associated with drug resistance and warrants further investigations.
Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, TX, USA.
Beining
B
Guo
Kamilia
K
Abdelraouf
Kimberly R
KR
Ledesma
Michael
M
Nikolaou
Vincent H
VH
Tam
D040981:Acinetobacter baumannii / Q000254:growth & development / Q000502:physiology*; D058491:Bacterial Load; D024881:Drug Resistance, Bacterial; D004734:Energy Metabolism; D006801:Humans; D008962:Models, Theoretical; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000502:physiology*; D013997:Time Factors