Bacterial fitness shapes the population dynamics of antibiotic-resistant and -susceptible bacteria in a model of combined antibiotic and anti-virulence treatment

DOI10.1016/J.JTBI.2015.02.011MaRDI QIDQ530477zbMATH OpenOpenAlexWikidataFDO

Authors Lucy Ternent, R. J. Dyson, Anne-Marie Krachler, Sara Jabbari

Publication date 1 August 2016

Published in Journal of Theoretical Biology (Search for Journal in Brave)

Copyright license Creative Commons Attribution 4.0 International

Full work available at URL https://arxiv.org/abs/1409.4238

zbMATH Keywords

anti-virulence drugsantibiotic resistancebacterial population dynamics

Mathematics Subject Classification ID

Medical applications (general) (92C50) Physiological, cellular and medical topics (92C99)

Abstract: Bacterial resistance to antibiotic treatment is a huge concern: introduction of any new antibiotic is shortly followed by the emergence of resistant bacterial isolates in the clinic. This issue is compounded by a severe lack of new antibiotics reaching the market. The significant rise in clinical resistance to antibiotics is especially problematic in nosocomial infections, where already vulnerable patients may fail to respond to treatment, causing even greater health concern. A recent focus has been on the development of anti-virulence drugs as a second line of defence in the treatment of antibiotic-resistant infections. This treatment, which weakens bacteria by reducing their virulence rather than killing them, should allow infections to be cleared through the body's natural defence mechanisms. In this way there should be little to no selective pressure exerted on the organism and, as such, a predominantly resistant population would be unlikely to emerge. However, much controversy surrounds this approach with many believing it would not be powerful enough to clear existing infections, restricting its potential application to prophylaxis. We have developed a mathematical model that provides a theoretical framework to reveal the circumstances under which anti-virulence drugs may or may not be successful. We demonstrate that by harnessing and combining the advantages of antibiotics with those provided by anti-virulence drugs, given infection-specific parameters, it is possible to identify treatment strategies that would efficiently clear bacterial infections, while preventing the emergence of resistant subpopulations. Our findings strongly support the continuation of research into anti-virulence drugs and demonstrate that their applicability may reach beyond infection prevention.

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Cites work

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• The dynamics of bacterial infection, innate immune response, and antibiotic treatment
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Cited in

(16)

• Exploring the role of the immune response in preventing antibiotic resistance
• Comparison of stochastic and random models for bacterial resistance
• Quantifying the impact of a periodic presence of antimicrobial on resistance evolution in a homogeneous microbial population of fixed size
• A mathematical model of the inflammatory response to pathogen challenge
• Phage-antibiotic synergy inhibited by temperate and chronic virus competition
• An agent-based lattice model for the emergence of anti-microbial resistance
• A new modeling approach to the effect of antimicrobial agents on heterogeneous microbial populations
• A unified inter-host and in-host model of antibiotic resistance and infection spread in a hospital ward
• Harnessing intra-host strain competition to limit antibiotic resistance: mathematical model results
• Optimal control and additive perturbations help in estimating ill-posed and uncertain dynamical systems
• Rational design of antibiotic treatment plans: a treatment strategy for managing evolution and reversing resistance
• The mathematical analysis of the model of antibiotic-resistant bacteria and the immune cells
• Large time behavior of nonautonomous differential systems modeling antibiotic‐resistant bacteria in rivers
• Interplay of virulence factors shapes ecology and treatment outcomes in polymicrobial infections
• Temporal and spatial dynamics of bacteria in rivers affected by pollution
• Dynamic analysis and optimal drug dosage control strategy of the effect of drug response on sensitive and resistant bacteria with continuous and impulsive infusion

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