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Single-cell analysis of multiple invertible promoters reveals differential inversion rates as a strong determinant of bacterial population heterogeneity

2023/08/04 by Freeman Lan, Jason Saba, Yili Qian +3 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Environmental Science · #Evolution and Genetic Dynamics #Gut microbiota and health #Microbial Community Ecology and Physiology

paper · pdf · doi:10.1126/sciadv.adg5476

openalex publication_date 2023/08/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Population heterogeneity can promote bacterial fitness in response to unpredictable environmental conditions. A major mechanism of phenotypic variability in the human gut symbiont Bacteroides spp. involves the inversion of promoters that drive the expression of capsular polysaccharides, which determine the architecture of the cell surface. High-throughput single-cell sequencing reveals substantial population heterogeneity generated through combinatorial promoter inversion regulated by a broadly conserved serine recombinase. Exploiting control over population diversification, we show that populations with different initial compositions converge to a similar composition over time. Combining our data with stochastic computational modeling, we demonstrate that the differential rates of promoter inversion are a major mechanism shaping population dynamics. More broadly, our approach could be used to interrogate single-cell combinatorial phase variable states of diverse microbes including bacterial pathogens.

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