Translating eco-evolutionary biology into therapy to tackle antibiotic resistance

Sanz-García, Fernando; Gil-Gil, Teresa; Laborda, Pablo; Blanco, Paula; Ochoa-Sánchez, Luz-Edith; Baquero, Fernando; Martínez, José Luis; Hernando-Amado, Sara

doi:10.1038/s41579-023-00902-5

Cited by 32 publications

(14 citation statements)

References 168 publications

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“…Identification of fitness deficits that are stable at the face of fitnesscompensation is a major step toward translation of evolutionary trade-offs into effective therapy. 72 The design of sequential antibiotic therapy is not trivial. The primary antibiotic must be selected such that the evolutionary pathways impose deficits that impede subsequent adaptation.…”

Section: ■ Discussionmentioning

confidence: 99%

“…The underlying reason behind this slowdown in evolution to STR could not be determined, but the inability to alleviate this slowdown even after multiple passes through SAGE medium suggests that this may be a stable phenotype. Identification of fitness deficits that are stable at the face of fitness-compensation is a major step toward translation of evolutionary trade-offs into effective therapy …”

Section: Discussionmentioning

confidence: 99%

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Fitness Costs of Antibiotic Resistance Impede the Evolution of Resistance to Other Antibiotics

Chowdhury,

Findlay

2023

ACS Infect. Dis.

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Antibiotic resistance is a major threat to global health, claiming the lives of millions every year. With a nearly dry antibiotic development pipeline, novel strategies are urgently needed to combat resistant pathogens. One emerging strategy is the use of sequential antibiotic therapy, postulated to reduce the rate at which antibiotic resistance evolves. Here, we use the soft agar gradient evolution (SAGE) system to carry out high-throughput in vitro bacterial evolution against antibiotic pressure. We find that evolution of resistance to the antibiotic chloramphenicol (CHL) severely affects bacterial fitness, slowing the rate at which resistance to the antibiotics nitrofurantoin and streptomycin emerges. In vitro acquisition of compensatory mutations in the CHL-resistant cells markedly improves fitness and nitrofurantoin adaptation rates but fails to restore rates to wild-type levels against streptomycin. Genome sequencing reveals distinct evolutionary paths to resistance in fitness-impaired populations, suggesting resistance trade-offs in favor of mitigation of fitness costs. We show that the speed of bacterial fronts in SAGE plates is a reliable indicator of adaptation rates and evolutionary trajectories to resistance. Identification of antibiotics whose mutational resistance mechanisms confer stable impairments may help clinicians prescribe sequential antibiotic therapies that are less prone to resistance evolution.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fitness Costs of Antibiotic Resistance Impede the Evolution of Resistance to Other Antibiotics

Chowdhury,

Findlay

2023

ACS Infect. Dis.

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“…Combating pathogens with a set of drugs, combining different inhibitory targets and mechanisms of action, rather than with an individual drug, is a promising strategy to combat pathogens (Bari et al, 2023 ; Sanz‐García et al, 2023 ). In addition, targeting microbial virulence mechanisms instead of survival, is likely to reduce the emergence of antimicrobial resistant strains (Allen et al, 2014 ).…”

Section: Final Remarksmentioning

confidence: 99%

Targeting motility and chemotaxis as a strategy to combat bacterial pathogens

Matilla

Krell

2023

Microbial Biotechnology

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“…This trade-off in resistance can be harnessed by targeting bacterial metabolism, providing a potential avenue for tackling antimicrobial resistance (AMR). This innovative approach is explored in-depth in a review by Sanz-García and colleagues ( Sanz-García et al., 2023 ). Furthermore, the principles of evolutionary game theory have given rise to adaptive therapy, which has demonstrated the capacity to influence the eco-evolutionary dynamics of cancer.…”

Section: Applications Of Edmentioning

confidence: 99%

Solving polymicrobial puzzles: evolutionary dynamics and future directions

Srinivasan,

Sajeevan,

Rajaramon

et al. 2023

Front. Cell. Infect. Microbiol.

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Polymicrobial infections include various microorganisms, often necessitating different treatment methods than a monomicrobial infection. Scientists have been puzzled by the complex interactions within these communities for generations. The presence of specific microorganisms warrants a chronic infection and impacts crucial factors such as virulence and antibiotic susceptibility. Game theory is valuable for scenarios involving multiple decision-makers, but its relevance to polymicrobial infections is limited. Eco-evolutionary dynamics introduce causation for multiple proteomic interactions like metabolic syntropy and niche segregation. The review culminates both these giants to form evolutionary dynamics (ED). There is a significant amount of literature on inter-bacterial interactions that remain unsynchronised. Such raw data can only be moulded by analysing the ED involved. The review culminates the inter-bacterial interactions in multiple clinically relevant polymicrobial infections like chronic wounds, CAUTI, otitis media and dental carries. The data is further moulded with ED to analyse the niche colonisation of two notoriously competitive bacteria: S.aureus and P.aeruginosa. The review attempts to develop a future trajectory for polymicrobial research by following recent innovative strategies incorporating ED to curb polymicrobial infections.

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Translating eco-evolutionary biology into therapy to tackle antibiotic resistance

Cited by 32 publications

References 168 publications

Fitness Costs of Antibiotic Resistance Impede the Evolution of Resistance to Other Antibiotics

Fitness Costs of Antibiotic Resistance Impede the Evolution of Resistance to Other Antibiotics

Targeting motility and chemotaxis as a strategy to combat bacterial pathogens

Solving polymicrobial puzzles: evolutionary dynamics and future directions

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