A Practical Guide to Measuring Mutation Rates in Antibiotic Resistance

Pope, Cassie F.; O’Sullivan, Denise M; McHugh, Timothy D.; Gillespie, Stephen H.

doi:10.1128/aac.01152-07

Cited by 76 publications

(73 citation statements)

References 32 publications

(33 reference statements)

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“…The process starts at time t = 0 when the wild-type, drugsensitive population reaches a size of exactly N 0 = 1/m, where m denotes the mutation rate per generation at which new mutant cells are produced [that is, we consider only the so-called Luria-Delbrück period (Rosche and Foster 2000;Refsland and Livingston 2005;Pope et al 2008)]. Since N 0 m = 1, the first resistant mutant, and therefore the first clone, appears when t = 0.…”

Section: Resultsmentioning

confidence: 99%

Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria

2016

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Any pathogen population sufficiently large is expected to harbor spontaneous drug-resistant mutants, often responsible for disease relapse after antibiotic therapy. It is seldom appreciated, however, that while larger populations harbor more mutants, the abundance distribution of these mutants is expected to be markedly uneven. This is because a larger population size allows early mutants to expand for longer, exacerbating their predominance in the final mutant subpopulation. Here, we investigate the extent to which this reduction in evenness can constrain the genetic diversity of spontaneous drug resistance in bacteria. Combining theory and experiments, we show that even small variations in growth rate between resistant mutants and the wild type result in orders-ofmagnitude differences in genetic diversity. Indeed, only a slight fitness advantage for the mutant is enough to keep diversity low and independent of population size. These results have important clinical implications. Genetic diversity at antibiotic resistance loci can determine a population's capacity to cope with future challenges (i.e., second-line therapy). We thus revealed an unanticipated way in which the fitness effects of antibiotic resistance can affect the evolvability of pathogens surviving a drug-induced bottleneck. This insight will assist in the fight against multidrug-resistant microbes, as well as contribute to theories aimed at predicting cancer evolution.

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Section: Resultsmentioning

confidence: 99%

Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria

2016

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“…These data show a maximum, or 'sweet spot', for the number of plated mutants that survive antibiotic exposure and grow into colonies (figure 1a). The fraction of the plated culture that gives rise to mutant colonies, also known as the 'mutation frequency' [25], decreases monotonically with increasing cell density (figure 1b). Therefore, the probability of a mutant growing into a colony must also decrease with increasing cell density.…”

Section: Statistical Testsmentioning

confidence: 99%

The spatial profiles and metabolic capabilities of microbial populations impact the growth of antibiotic-resistant mutants

Kaushik

Ratnayeke

Katira

et al. 2015

J. R. Soc. Interface.

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Antibiotic resistance adversely affects clinical and public health on a global scale. Using the opportunistic human pathogen Pseudomonas aeruginosa, we show that increasing the number density of bacteria, on agar containing aminoglycoside antibiotics, can non-monotonically impact the survival of antibiotic-resistant mutants. Notably, at high cell densities, mutant survival is inhibited. A wide range of bacterial species can inhibit antibiotic-resistant mutants. Inhibition results from the metabolic breakdown of amino acids, which results in alkaline by-products. The consequent increase in pH acts in conjunction with aminoglycosides to mediate inhibition. Our work raises the possibility that the manipulation of microbial population structure and nutrient environment in conjunction with existing antibiotics could provide therapeutic approaches to combat antibiotic resistance.

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“…In addition, some small-area and short-duration (<1 h) operations also used antibacterial agents. Thus, the prophylactic medication indications were apparently not strictly mastered (Pope et al, 2008). The misuse of antibacterial agents not only enables the drug resistance of bacteria to develop, but also unnecessarily incurs cost (Maragakis et al, 2008).…”

Section: Indications For Prophylactic Use Of Antibacterial Agentsmentioning

confidence: 99%

A multi-center study on the prophylactic application of antibiotics in aseptic operations

Ma¹,

Liu²,

Wang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT.To understand the application of antibacterial agents in aseptic operations and to provide evidence for their rational use and management, the antibiotic use statuses of six types of aseptic operations (306 cases from 4 tertiary hospitals) were retrospectively analyzed. Of 312 patients, 306 (65.08%) were treated with antibacterial agents in the perioperative period. Four categories of antibiotics including cephalosporins, penicillins, nitroimidazoles, and fluoroquinolones were administered (descending sequence). Administration time: preoperative >2 h, 15 cases; preoperative 0.5-2 h, 20 cases; postoperative: 265 cases. Drug withdrawal time: postoperative 1-3 days: 33 cases; 3-7 days: 255 cases; 7-15 days: 12 cases. The prophylactic use of antibacterial agents in aseptic operations suffers from non-strict mastered medication indication, improper drug selection, aimless drug combinations, inappropriate administration timing, and over long medication duration.

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A Practical Guide to Measuring Mutation Rates in Antibiotic Resistance

Cited by 76 publications

References 32 publications

Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria

Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria

The spatial profiles and metabolic capabilities of microbial populations impact the growth of antibiotic-resistant mutants

A multi-center study on the prophylactic application of antibiotics in aseptic operations

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