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Biology subjects

Newton, D. P.

Publications and source records attributed to Newton, D. P..

2 recordsLinked to original sources

Antibiotic effects on microbial communities are modulated by resource competition

Antibiotic treatment significantly impacts the human gut microbiota, but quantitative understanding of how antibiotics affect community diversity is lacking. Here, we build on classical ecological models of resource competition to investigate community responses to antibiotic-induced species-specific death rates. Our analyses highlight the complex dependence of species coexistence that can arise from the interplay of resource competition and antibiotic activity, independent of other biological mechanisms. We show that resource competition can cause richness to change non-monotonically as antibiotic concentrations are increased. We identified resource competition structures that cause richness to depend on the order of sequential application of antibiotics (non-transitivity), and the emergence of synergistic and antagonistic effects under simultaneous application of multiple antibiotics (non-additivity). These complex behaviors can be prevalent, especially when generalist consumers are targeted. Communities can be prone to either synergism or antagonism, but typically not both, and antagonism is more common. Furthermore, we identify a striking overlap in competition structures that lead to non-transitivity during antibiotic sequences and those that lead to non-additivity during antibiotic combination, suggesting that our analysis is broadly applicable across a wide range of clinically relevant antibiotic treatment schemes. In sum, our results will facilitate the engineering of community dynamics via deleterious agents.

ecology↗

Construction and characterization of a genome-scale ordered mutant collection of Bacteroides thetaiotaomicron

Genomic analyses have revealed how the gut microbiota impacts human health. However, knowledge about the physiology of most gut commensals is largely lacking. Here, we sorted cells from a pooled library to construct an ordered collection of transposon-insertion mutants in the model commensal Bacteroides thetaiotaomicron. We applied a pooling strategy with barcode sequencing to locate mutants and created a condensed collection with single insertions in 2,565 genes. This effort enabled the development of an accurate model for progenitor-collection assembly, which identified strain-abundance biases and multi-insertion strains as important factors that limit coverage. To demonstrate the potential for phenotypic screening, we analyzed growth dynamics and morphology of the condensed collection and identified growth defects and altered cell shape in the sphingolipid-synthesis gene BT0870 and the thiamine scavenging gene BT2397. Analyses of this collection and utilization of the platform described herein to construct future ordered libraries will increase understanding of gut commensal physiology and colonization strategies.

microbiology↗