Nongenetic Individuality in the Host–Phage Interaction

Abstract

Isogenic bacteria can exhibit a range of phenotypes, even in homogeneous environmental conditions. Such nongenetic individuality has been observed in a wide range of biological processes, including differentiation and stress response. A striking example is the heterogeneous response of bacteria to antibiotics, whereby a small fraction of drug-sensitive bacteria can persist under extensive antibiotic treatments. We have previously shown that persistent bacteria enter a phenotypic state, identified by slow growth or dormancy, which protects them from the lethal action of antibiotics. Here, we studied the effect of persistence on the interaction between Escherichia coli and phage lambda. We used long-term time-lapse microscopy to follow the expression of green fluorescent protein (GFP) under the phage lytic promoter, as well as cellular fate, in single infected bacteria. Intriguingly, we found that, whereas persistent bacteria are protected from prophage induction, they are not protected from lytic infection. Quantitative analysis of gene expression reveals that the expression of lytic genes is suppressed in persistent bacteria. However, when persistent bacteria switch to normal growth, the infecting phage resumes the process of gene expression, ultimately causing cell lysis. Using mathematical models for these two host–phage interactions, we found that the bacteria's nongenetic individuality can significantly affect the population dynamics, and might be relevant for understanding the coevolution of bacterial hosts and phages.

The Frequency of Persisters in Escherichia coli Reflects the Kinetics of Awakening from Dormancy

“…While normal cells are believed to resume growth and become susceptible to antibiotics immediately after transfer into fresh medium, persisters remain dormant longer (28). Here we demonstrate that heterogeneous growth resumption is an intrinsic property of the whole E. coli population.…”

HipA-Triggered Growth Arrest and -Lactam Tolerance in Escherichia coli Are Mediated by RelA-Dependent ppGpp Synthesis

“…Having found that HipA-arrested cells are fully metabolically active, we next sought to exploit the active carbon flux within HipAarrested cells to produce useful compounds via synthetic pathways. One advantage of using growth-arrested bacteria as a platform for the production of chemicals might be their higher resistance to phage-induced lysis compared with that of growing cells (38). Industrial-scale fermentations are extremely vulnerable to contamination by phage, which often causes considerable production losses.…”

Polyfunctional responses by human T cells result from sequential release of cytokines

“…The capability of T cells to access multiple programs for cytokine release allows diverse and dynamically evolvable contributions to the sustained accumulation of cytokines in the global milieu, and such behavior represents an intriguing manifestation of modularity, cell-to-cell communication, and feedback. The adaptability of multicellular systems to temporal and environmental fluctuations is yet another quality that improves when the collective population comprises phenotypically diverse individuals (34)(35)(36). Dynamically evolving functional responses by T cells, therefore, suggest an alternate form of functional plasticity (37) and may provide yet another means for the immune system to adaptively respond to perturbations.…”