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The cost of antibiotic resistance depends on evolutionary history in Escherichia coli.

ABSTRACT: BACKGROUND:The persistence of antibiotic resistance depends on the fitness effects of resistance elements in the absence of antibiotics. Recent work shows that the fitness effect of a given resistance mutation is influenced by other resistance mutations on the same genome. However, resistant bacteria acquire additional beneficial mutations during evolution in the absence of antibiotics that do not alter resistance directly but may modify the fitness effects of new resistance mutations. RESULTS:We experimentally evolved rifampicin-resistant and sensitive Escherichia coli in a drug-free environment, before measuring the effects of new resistance elements on fitness in antibiotic-free conditions. Streptomycin-resistance mutations had small fitness effects in rifampicin-resistant genotypes that had adapted to antibiotic-free growth medium, compared to the same genotypes without adaptation. We observed a similar effect when resistance was encoded by a different mechanism and carried on a plasmid. Antibiotic-sensitive bacteria that adapted to the same conditions showed the same pattern for some resistance elements but not others. CONCLUSIONS:Epistatic variation of costs of resistance can result from evolution in the absence of antibiotics, as well as the presence of other resistance mutations.

SUBMITTER: Angst DC

PROVIDER: S-EPMC3751127 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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The cost of antibiotic resistance depends on evolutionary history in Escherichia coli.

Angst Daniel C DC Hall Alex R AR

BMC evolutionary biology 20130802

<h4>Background</h4>The persistence of antibiotic resistance depends on the fitness effects of resistance elements in the absence of antibiotics. Recent work shows that the fitness effect of a given resistance mutation is influenced by other resistance mutations on the same genome. However, resistant bacteria acquire additional beneficial mutations during evolution in the absence of antibiotics that do not alter resistance directly but may modify the fitness effects of new resistance mutations.<h ...[more]

PMID: 23914906

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Project description:Biofilms are considered to be highly resistant to antimicrobial agents. Several mechanisms have been proposed to explain this high resistance of biofilms, including restricted penetration of antimicrobial agents into biofilms, slow growth owing to nutrient limitation, expression of genes involved in the general stress response, and emergence of a biofilm-specific phenotype. However, since combinations of these factors are involved in most biofilm studies, it is still difficult to fully understand the mechanisms of biofilm resistance to antibiotics. In this study, the antibiotic susceptibility of Escherichia coli cells in biofilms was investigated with exclusion of the effects of the restricted penetration of antimicrobial agents into biofilms and the slow growth owing to nutrient limitation. Three different antibiotics, ampicillin (100 microg/ml), kanamycin (25 microg/ml), and ofloxacin (10 microg/ml), were applied directly to cells in the deeper layers of mature biofilms that developed in flow cells after removal of the surface layers of the biofilms. The results of the antibiotic treatment analyses revealed that ofloxacin and kanamycin were effective against biofilm cells, whereas ampicillin did not kill the cells, resulting in regrowth of the biofilm after the ampicillin treatment was discontinued. LIVE/DEAD staining revealed that a small fraction of resistant cells emerged in the deeper layers of the mature biofilms and that these cells were still alive even after 24 h of ampicillin treatment. Furthermore, to determine which genes in the biofilm cells are induced, allowing increased resistance to ampicillin, global gene expression was analyzed at different stages of biofilm formation, the attachment, colony formation, and maturation stages. The results showed that significant changes in gene expression occurred during biofilm formation, which were partly induced by rpoS expression. Based on the experimental data, it is likely that the observed resistance of biofilms can be attributed to formation of ampicillin-resistant subpopulations in the deeper layers of mature biofilms but not in young colony biofilms and that the production and resistance of the subpopulations were aided by biofilm-specific phenotypes, like slow growth and induction of rpoS-mediated stress responses.

Project description:UnlabelledEscherichia colisequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. This study of the largest worldwide collection (n= 215) of sequenced ST131E. coliisolates to date demonstrates that the clonal expansion of two previously recognized antimicrobial-resistant clades, C1/H30R and C2/H30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/H30Rx clade driven by the acquisition of ablaCTX-M-15-containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX-M resistance plasmids and chromosomal integration ofblaCTX-Mwithin subclusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed among ST131, theblaCTX-M-14/14-likegroup. The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages ofE. coli These data also highlight the global imperative to reduce specific antibiotic selection pressures and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages.ImportanceEscherichia coli, perennially a major bacterial pathogen, is becoming increasingly difficult to manage due to emerging resistance to all preferred antimicrobials. Resistance is concentrated within specificE. colilineages, such as sequence type 131 (ST131). Clarification of the genetic basis for clonally associated resistance is key to devising intervention strategies. We used high-resolution genomic analysis of a large global collection of ST131 isolates to define the evolutionary history of extended-spectrum beta-lactamase production in ST131. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance elements. Both global distribution and regional segregation were evident. The diversity of resistance element acquisition and propagation within ST131 indicates a need for control and surveillance strategies that target both bacterial strains and mobile genetic elements.

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The cost of antibiotic resistance depends on evolutionary history in Escherichia coli.

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The cost of antibiotic resistance depends on evolutionary history in Escherichia coli.

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