Bacterial population dynamics during colonization of tumors
Bacterial colonization of solid cancer tumors can happen. Despite its clinical importance, little is known about the colonization process itself. We monitored tumor colonization in a mouse model by intravenous injection of genetically barcoded Escherichia coli cells and sequencing them from resected tumors. Our experiments showed that out of millions of infecting cells, only a few dozen successfully colonized the tumor and rapidly proliferated to saturate the niche within less than a day. Sequencing results further revealed that seeding bacteria generated progenies with highly uneven sizes. We further studied the forces dictating population structure by repeating the experiments with intratumor injections that circumvented infection bottlenecks. We observed that progenies sizes were still highly skewed and consistently followed a scale-free distribution matching Zipf's law. Mathematical modeling consistent with our experimental observations suggested that colonization follows a two-phase process: Initially, rare and independent infection events allow opportunistic bacteria to rapidly expand and take over the favorable niche. Once bacterial load saturates, progenies cycle through rapid growth and contraction cycles that give rise to a distinctive population structure that matches Zipf's law. Our work explains why the tumors are characterized by low-complexity microbiomes relative to the more complex microbiome typical to natural body sites.