Abstract
Microbial communities are shaped by bacteriophages through predation and lysogeny. A better understanding of the interactions between these processes across different types of environments is key to elucidate how phages mediate microbial competition and to design efficient phage therapies. We introduce an individual-based model (eVIVALDI) to investigate the role of environmental structure in the elimination of a population with a combined treatment of antibiotics and virulent phages, and in the invasion of a population of phage-sensitive bacteria by lysogens. We show that structured environments facilitate the emergence of double resistance, to antibiotics and phages, due to limited diffusion of phage particles and increased nutrient availability from dead cells. They also hinder phage amplification, thus decreasing the generation of phage genetic diversity and increasing the unpredictability of phage-bacteria arms-races. We used a machine learning approach to determine the variables most important for the invasion of sensitive populations by lysogens. They revealed that phage-associated traits and environmental structure are the key drivers of the process. Structured environments hinder invasions, and accounting for their existence improves the fit of the model to published in vivo experimental data. Our results underline environmental structure as key to understand in vivo phage-bacteria interactions.
Highlights
Microbial organisms are pervasive across all natural environments, including the human body
Bacterial pathogens are more likely to be lysogens[15], and many of their temperate phages encode virulence factors[16]. Even if this has restricted the development of phage therapy to the use of virulent phages, the role of temperate phages in this process is important because virions arising from prophage induction can infect closely related competitor bacteria that are non-lysogenic for the phage, decreasing bacterial competition, increasing prophage frequency, and liberating resources for the growth of the remaining lysogens[17]
Outcomes of simultaneous antibiotic and phage therapy depend on environmental structure
Summary
Microbial organisms are pervasive across all natural environments, including the human body. These models become much more complex, or even intractable, when tackling multiple mechanisms, spatial heterogeneity, and intrinsically stochastic process (such as mutation-selection-drift and lysis-lysogeny decisions), as found in most natural communities[26,27,28,29,30] This may explain why these models sometimes fail to fully reproduce in vivo dynamics of phage infection[19], or the lack of theoretical studies regarding the effects of treatments using both virulent phages and antibiotic to curb bacterial infections in more realistic (structured) environments[19,31,32]. We find that structured environments, when compared to well-mixed environments, lead to a better fit of previous experimental results of the effects of lysogeny in vivo
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