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Survival of bactericidal antibiotic treatment by a persister subpopulation of Listeria monocytogenes.

ABSTRACT: Listeria monocytogenes can cause the serious infection listeriosis, which despite antibiotic treatment has a high mortality. Understanding the response of L. monocytogenes to antibiotic exposure is therefore important to ensure treatment success. Some bacteria survive antibiotic treatment by formation of persisters, which are a dormant antibiotic-tolerant subpopulation. The purpose of this study was to determine whether L. monocytogenes can form persisters and how bacterial physiology affects the number of persisters in the population. A stationary-phase culture of L. monocytogenes was adjusted to 10(8) CFU ml(-1), and 10(3) to 10(4) CFU ml(-1) survived 72-h treatment with 100 ?g of norfloxacin ml(-1), indicating a persister subpopulation. This survival was not caused by antibiotic resistance as regrown persisters were as sensitive to norfloxacin as the parental strain. Higher numbers of persisters (10(5) to 10(6)) were surviving when older stationary phase or surface-associated cells were treated with 100 ?g of norfloxacin ml(-1). The number of persisters was similar when a ?sigB mutant and the wild type were treated with norfloxacin, but the killing rate was higher in the ?sigB mutant. Dormant norfloxacin persisters could be activated by the addition of fermentable carbohydrates and subsequently killed by gentamicin; however, a stable surviving subpopulation of 10(3) CFU ml(-1) remained. Nitrofurantoin that has a growth-independent mode of action was effective against both growing and dormant cells, suggesting that eradication of persisters is possible. Our study adds L. monocytogenes to the list of bacterial species capable of surviving bactericidal antibiotics in a dormant stage, and this persister phenomenon should be borne in mind when developing treatment regimens.

SUBMITTER: Knudsen GM

PROVIDER: S-EPMC3837754 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Survival of bactericidal antibiotic treatment by a persister subpopulation of Listeria monocytogenes.

Knudsen Gitte M GM Knudsen Gitte M GM Ng Yin Y Gram Lone L

Applied and environmental microbiology 20130920 23

Listeria monocytogenes can cause the serious infection listeriosis, which despite antibiotic treatment has a high mortality. Understanding the response of L. monocytogenes to antibiotic exposure is therefore important to ensure treatment success. Some bacteria survive antibiotic treatment by formation of persisters, which are a dormant antibiotic-tolerant subpopulation. The purpose of this study was to determine whether L. monocytogenes can form persisters and how bacterial physiology affects th ...[more]

PMID: 24056460

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Project description:Between January and July 2021, there were as many as 30 recalls in the U.S. due to potential Listeria monocytogenes contamination from a variety of food products including muffins, kimchi, chicken salad, ready-to-eat chicken, smoked fish, mushrooms, queso fresco cheese, ice cream, turkey sandwiches, squash, and other foods. A contaminated food chain can serve as a potential vehicle for transmitting antibiotic resistant bacteria since there is a slow emergence of multi-drug antibiotic resistance in L. monocytogenes. Biocides are essential for safe food processing, but they may also induce unintended selective pressure at sublethal doses for the expression of antibiotic resistance in L. monocytogenes. To better understand the sources of such slow emergence of antibiotic resistance through biocide residues present in the food environments, we are working on the role of sublethal doses of commonly used biocides in defined broth and water models for understanding L. monocytogenes adaptation. We recently published the development of low-level tolerance to fluoroquinolone antibiotic ciprofloxacin in quaternary ammonium compound (QAC) adapted subpopulations of L. monocytogenes (Microorganisms 9, 1052). Of the six different antibiotics tested to determine heterologous stress adaptation in eight strains of L. monocytogenes, trimethoprim was the second one that exhibited low-level tolerance development after continuous exposure (by three approaches) to sublethal concentrations of QAC against actively growing planktonic cells of L. monocytogenes. When adapted to daily cycles of fixed or gradually increasing sublethal concentrations of QAC, we observed three main findings in eight L. monocytogenes strains against trimethoprim: (a) 3 of the 8 strains exhibited significant increase in short-range minimum inhibitory concentration (MIC) of trimethoprim by 1.7 to 2.5 fold in QAC-adapted subpopulations compared to non-adapted cells (p < 0.05); (b) 2 of the 8 strains exhibited significant increase in growth rate in trimethoprim (optical density (OD) by 600 nm at 12 h) by 1.4 to 4.8 fold in QAC-adapted subpopulations compared to non-adapted cells (p < 0.05); and (c) 5 of the 8 strains yielded significantly higher survival by 1.3-to-3.1 log CFU/mL in trimethoprim in QAC-adapted subpopulations compared to the non-adapted control (p < 0.05). However, for 3/8 strains of L. monocytogenes, there was no increase in the survival of QAC-adapted subpopulations compared to non-adapted control in trimethoprim. These findings suggest the potential formation of low-level trimethoprim tolerant subpopulations in some L. monocytogenes strains where QAC may be used widely. These experimental models are useful in developing early detection methods for tracking the slow emergence of antibiotic tolerant strains through food chain. Also, these findings are useful in understanding the predisposing conditions leading to slow emergence of antibiotic resistant strains of L. monocytogenes in various food production and food processing environments.

Dataset Information

Survival of bactericidal antibiotic treatment by a persister subpopulation of Listeria monocytogenes.

Publications

Survival of bactericidal antibiotic treatment by a persister subpopulation of Listeria monocytogenes.

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