Multi-strain phage induced clearance of bacterial infections

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 7, 2024

Bacteriophage (or ‘phage’ – viruses that infect and kill bacteria) are increasingly considered as a therapeutic alternative to treat antibiotic-resistant bacterial infections. However, bacteria can evolve resistance phage, presenting significant challenge the near- long-term success of phage therapeutics. Application mixtures multiple (i.e., ‘cocktails’) have been proposed limit emergence phage-resistant mutants could lead failure. Here, we combine theory computational models in vivo therapy study efficacy cocktail, composed two complementary phages motivated by example Pseudomonas aeruginosa facing exploit different surface receptors, LUZ19v PAK P1. As confirmed Luria-Delbrück fluctuation test, this motivating serves model for instances where extremely unlikely develop simultaneous mutations against both phages. We then quantify outcomes given single- or double-phage treatment models, function traits host immune strength. Building upon prior work showing monophage immunocompetent hosts, here show cocktails comprised targeting independent receptors improve outcome immunocompromised hosts reduce chance pathogens simultaneously combinations. The finding cocktail is qualitatively robust differences virus-bacteria interactions dynamics. Altogether, combined use analysis highlights influence viral life history receptor complementarity when designing deploying hosts.

Язык: Английский

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Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infections

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Abstract Pseudomonas aeruginosa causes antibiotic-resilient acute and chronic pneumonia, but the mechanisms by which it adapts to airway environment are poorly understood. Here, we investigated P. pathoadaptive in tissue-engineered human organoids. Using transposon sequencing situ, decoded how survives on mucosal surface during antibiotic treatment. Biofilm formation emerged as a major driver of colonization. Mutants that extensively produce biofilms mucus show limited exploratory behavior, limits nutrient access, slowing down their growth. Conversely, biofilm-dwelling better tolerate antibiotics via biophysical mechanisms. Finally, can shelter less-tolerant more cytotoxic strains, thereby contributing genotypic heterogeneity. must therefore adapt conflicting physical biological selective pressures initiate infections.

Язык: Английский

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Microtopographic Influence on Bacterial Biofilm Development in Habitat-Like Environments

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер unknown, С. 106311 - 106311

Опубликована: Окт. 1, 2024

Язык: Английский

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Tailored multilayer nanoparticles against resistant P. aeruginosa by disrupting the thickened mucus, dense biofilm and hyperinflammation

Journal of Controlled Release, Год журнала: 2024, Номер 378, С. 588 - 604

Опубликована: Дек. 25, 2024

Язык: Английский

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