Scale-dependent tipping points of bacterial colonization resistance

Abstract

Bacteria are efficient colonizers of a wide range of secluded micro-habitats, such as soil pores, skin follicles, dental cavities or crypts in gut-like environments. Although numerous factors promoting or obstructing stable colonization have been identified, we currently lack systematic approaches to explore how population stability and resilience depend on the scale of the micro-habitat. Using a microfluidic device to grow bacteria in crypt-like incubation chambers of systematically varied lengths, we found that the incubation scale can sensitively tune bacterial colonization success and resistance against invaders. Small crypts are un-colonizable, intermediately sized crypts can stably support dilute populations, while beyond a second critical lengthscale, populations phase-separate into a dilute and a jammed region. We demonstrate that the jammed state confers extreme colonization resistance, even if the resident strain is suppressed by an antibiotic. Combined with a flexible biophysical model, we show that scale acts as an environmental filter that can be tuned via the competition between growth and collective cell motion. More broadly, our observations underscore that scale can profoundly bias experimental outcomes in microbial ecology. Systematic, flow-adjustable lengthscale variations may serve as a promising strategy to elucidate further scale-sensitive tipping points and to rationally modulate the stability and resilience of microbial colonizers.

Anatomy promotes neutral coexistence of strains in the human skin microbiome

“…In addition, genetic drift may be favored because the number of cells that are actually growing might be substantially smaller than the census population (e.g., if bacterial replication were restricted to the very bottom of the follicle) (Hartl and Clark, 2006). In the case of a narrow growth region, physical crowding of cells inside a pore (Jahns and Alexeyev, 2014;Plewig et al, 2019) may exclude beneficial mutants from the growth layer (Schreck et al, 2019;Karita et al, 2021). These proposed mechanisms emphasize how host anatomy has the potential to suppress selective forces and tip the balance toward more neutral outcomes.…”

Ecological Stability Emerges at the Level of Strains in the Human Gut Microbiome

“…How and why closely related strains coexist in the human gut is one of the central biological questions raised by our results. Spatial segregation between strains, perhaps occupying different colonic crypts, or partitioning luminal and mucosal niches, could contribute to the observed pattern of strain coexistence [33, 42, 82], much as it does among Cutibacterium acnes strains inhabiting different pores on the facial microbiome [57]. However, spatial structure is far from the only mechanism that can foster coexistence between strains.…”

Propagation of Recombinant Genes through Complex Microbiomes with Synthetic Mini-RP4 Plasmid Vectors

“…Alas, rational modification of a standing microbial network is often limited by the well-known phenomenon of colonization resistance (CR), i.e., the ability of well-balanced communities to prevent or inhibit the establishment of foreign members [5]. This can be due to a variety of factors, including physical barriers, production of inhibitory compounds, injection of toxins, metabolic incompatibility, and others [6][7][8]. An alternative to adding new partners to an existing group is the delivery and spreading of the DNA encoding the functions of interest through the standing assembly, in such a way that the whole may acquire novel traits without necessarily changing the earlier structure or composition [6,9].…”