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The evolution of hypermutators in response to antibiotic treatment in both clinical and laboratory settings provides a unique context for the study of adaptive evolution. With increased mutation rates, the number of hitchhiker mutations within an evolving hypermutator population is remarkably high and presents substantial challenges in determining which mutations are adaptive. Intriguingly however, hypermutators also provide an opportunity to explore deeply the accessible evolutionary trajectories that lead to increased organism fitness, in this case the evolution of antibiotic resistance to the clinically relevant antibiotic tigecycline by the hospital pathogen Acinetobacter baumannii. Using a continuous culture system, AB210M, a clinically derived strain of A. baumannii, was evolved to tigecycline resistance. Analysis of the adapted populations showed that nearly all the successful lineages became hypermutators via movement of a mobile element to inactivate mutS. In addition, metagenomic analysis of population samples revealed another 896 mutations that occurred at a frequency greater than 5% in the population, while 38 phenotypically distinct individual colonies harbored a total of 1712 mutations. These mutations were scattered throughout the genome and affected ~40% of the coding sequences. The most highly mutated gene was adeS, a known tigecycline-resistance gene; however, adeS was not solely responsible for the high level of TGC resistance. Sixteen other genes stood out as potentially relevant to increased resistance. The five most prominent candidate genes (adeS, rpsJ, rrf, msbA, and gna) consistently re-emerged in subsequent replicate population studies suggesting they are likely to play a role in adaptation to tigecycline. Interestingly, the repeated evolution of a hypermutator phenotype in response to antibiotic stress illustrates not only a highly adaptive strategy to resistance, but also a remarkably efficient survey of successful evolutionary trajectories.
This article was published in the following journal.
Name: PloS one
Acinetobacter baumannii meningitis and ventriculitis are difficult issues, due to the low diffusion of antibiotics in the cerebrospinal fluid (CSF) and bacterial multidrug resistance. The presence of ...
Acinetobacter baumannii is an aerobic and Gram-negative bacterial pathogen with high morbidity and mortality. It remains a serious public health problem arising from its multidrug-resistant and extens...
Acinetobacter baumannii is one of the most frequent Gram-negative opportunistic pathogens associated with hospital-acquired infection worldwide. We briefly describe A. baumannii isolates that were rec...
Acinetobacter baumannii is a Gram-negative opportunistic pathogen and a leading cause of ventilator-associated pneumonia. Murine models of A. baumannii lung infection allow researchers to experimental...
Acinetobacter baumannii can cause severe nosocomial and community-acquired pneumonia. To study the pathogenesis of A. baumannii and develop new treatments, appropriate mouse models are needed. Most of...
The present study was designed to study the impact of empirical treatment with colistin empirical monotherapy and combined treatment with tigecycline and vancomycin on mortality of bactere...
The purpose of the present study is to evaluate the effects of immune function on prognositic outcome in critical ill patients with Acinetobacter baumannii infection.
Acinetobacter baumannii is an opportunist pathogen that has become increasingly important over recent years as a cause of nosocomial infections. Ventilator-associated pneumonia, central li...
This is a 2-part study, with Part A being the randomized, controlled portion of the study in patients with ABC (Acinetobacter Baumannii-calcoaceticus Complex) hospital-acquired bacterial p...
The investigators aimed to confirm the utility of the synergy test results (E-tesT) in vitro to predict the efficacy and safety of colistin-rifampin combination and colistin monotherapy in...
The ability of a cell to change its PHENOTYPE in response to changes in the environment.
A species of gram-negative, aerobic bacteria, commonly found in the clinical laboratory, and frequently resistant to common antibiotics.
Infections with bacteria of the genus ACINETOBACTER.
The quality or state of being able to be bent or creased repeatedly. (From Webster, 3d ed)
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
MRSA (methicillin-resistant Staphylococcus aureus)
MRSA (methicillin-resistant Staphylococcus aureus) is a family of bacteria with resistance to one or more major antibiotics. There are currently 17 different strains of MRSA. Two particular strains, EMRSA15 and EMRSA16 account for 96% of MRSA blood...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Stress is caused by your perception of situations around you and then the reaction of your body to them. The automatic stress response to unexpected events is known as 'fight or flight'. Discovered by Walter Cannon in 1932, it is the release of h...