title: Fitness and proteome changes accompanying the development of erythromycin resistance in a population of Escherichia coli grown in continuous culture.
abstract: We studied the impact of a sublethal concentration of erythromycin on the fitness and proteome of a continuously cultivated population of Escherichia coli. The development of resistance to erythromycin in the population was followed over time by the gradient plate method and minimum inhibitory concentration (MIC) measurements. We measured the growth rate, standardized efficiency of synthesis of radiolabeled proteins, and translation accuracy of the system. The proteome changes were followed over time in two parallel experiments that differed in the presence or absence of erythromycin. A comparison of the proteomes at each time point (43, 68, and 103 h) revealed a group of unique proteins differing in expression. From all 35 proteins differing throughout the cultivation, only three were common to more than one time point. In the final population, a significant proportion of upregulated proteins was localized to the outer or inner cytoplasmic membranes or to the periplasmic space. In a population growing for more than 100 generations in the presence of antibiotic, erythromycin-resistant bacterial clones with improved fitness in comparison to early resistant culture predominated. This phenomenon was accompanied by distinct changes in protein expression during a stepwise, population-based development of erythromycin resistance.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Denisa
authors.initials: D
authors.lastname: Petráčková
authors.forename: Jiří
authors.initials: J
authors.lastname: Janeček
authors.forename: Silvia
authors.initials: S
authors.lastname: Bezoušková
authors.forename: Ladislava
authors.initials: L
authors.lastname: Kalachová
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Techniková
authors.forename: Karolína
authors.initials: K
authors.lastname: Buriánková
authors.forename: Petr
authors.initials: P
authors.lastname: Halada
authors.forename: Kateřina
authors.initials: K
authors.lastname: Haladová
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Weiser
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003470:Culture Media; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004917:Erythromycin / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D056084:Genetic Fitness / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D029968:Escherichia coli Proteins; D020543:Proteome; D004917:Erythromycin
keywords: Continuous cultivation system; Escherichia coli; erythromycin; fitness; proteome; resistance