Oscillatory dynamics in a bacterial cross-protection mutualism

Abstract

Cooperation between microbes can enable microbial communities to survive in harsh environments. Enzymatic deactivation of antibiotics, a common mechanism of antibiotic resistance in bacteria, is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. Understanding how bacterial populations survive antibiotic exposure is important both clinically and ecologically, yet the implications of cooperative antibiotic deactivation on the population and evolutionary dynamics remain poorly understood, particularly in the presence of more than one antibiotic. Here, we show that two Escherichia coli strains can form an effective crossprotection mutualism, protecting each other in the presence of two antibiotics (ampicillin and chloramphenicol) so that the coculture can survive in antibiotic concentrations that inhibit growth of either strain alone. Moreover, we find that daily dilutions of the coculture lead to large oscillations in the relative abundance of the two strains, with the ratio of abundances varying by nearly four orders of magnitude over the course of the 3-day period of the oscillation. At modest antibiotic concentrations, the mutualistic behavior enables long-term survival of the oscillating populations; however, at higher antibiotic concentrations, the oscillations destabilize the population, eventually leading to collapse. The two strains form a successful cross-protection mutualism without a period of coevolution, suggesting that similar mutualisms may arise during antibiotic treatment and in natural environments such as the soil.

Collective Resistance in Microbial Communities by Intracellular Antibiotic Deactivation

“…Our work with CAT and pneumococcus extends the known phenomenon of passive resistance via β-lactamase expression and expands on recent findings of collective resistance of bacterial communities [29,30]. Intracellular antibiotic deactivation requires a high drug permeability, and it is worth noting that this—in general desired—drug characteristic can also represent a risk factor for the effectiveness of an antibiotic therapy.…”

“…Our results expand recent findings on the basis of E . coli growth cultures and indicate a potential clinical relevance of passive Cm resistance [29,30]. …”

Phosphorylation-induced conformational dynamics in an intrinsically disordered protein and potential role in phenotypic heterogeneity

“…Furthermore, contrary to a "binary" model that assumes PCa cells to have an androgen-dependent or -independent phenotype, subpopulations of partially androgen-dependent and androgen-independent cells can also drive tumor progression synergistically through cell-to-cell communication as observed in some cases. For example, two E. coli strains can protect each other in the presence of two antibiotics (52). Similarly, a cluster of circulating tumor cells (CTCs) with "partial" phenotypes forms 50-fold more secondary tumors compared with the same number of individual CTCs (53).…”

Antibiotic efficacy — context matters

“…In support of this, several studies demonstrate how persister mechanisms can help pathogens survive inside host cells [94,95] and provide a reservoir for evolving antibiotic resistance [96-98]. Investigations have also shown how social behaviors such as quorum sensing [99], signaling [100] and cooperative mutualism [101] can confer protection against antibiotic lethality in mixed-species environments. Nascent studies on population-level responses to antibiotic treatment have revealed several intra- and inter-species mechanisms for collective protection [102,103], but such experiments are challenging due to scale.…”