Lag Phase Is a Dynamic, Organized, Adaptive, and Evolvable Period That Prepares Bacteria for Cell Division

Abstract

Lag is a temporary period of nonreplication seen in bacteria that are introduced to new media. Despite latency being described by Müller in 1895, only recently have we gained insights into the cellular processes characterizing lag phase. This review covers literature to date on the transcriptomic, proteomic, metabolomic, physiological, biochemical, and evolutionary features of prokaryotic lag. Though lag is commonly described as a preparative phase that allows bacteria to harvest nutrients and adapt to new environments, the implications of recent studies indicate that a refinement of this view is well deserved. As shown, lag is a dynamic, organized, adaptive, and evolvable process that protects bacteria from threats, promotes reproductive fitness, and is broadly relevant to the study of bacterial evolution, host-pathogen interactions, antibiotic tolerance, environmental biology, molecular microbiology, and food safety.

Keywords: antibiotic tolerance; bet-hedging; cell division; food safety; gene expression; host-pathogen interactions; oxidative stress; persister cells; phenotype switching; primary metabolism.

FIG 1

A representative growth plot of a bacterial culture. Where the dotted lines cross is the commonly defined endpoint of the lag period for a bacterial culture. For individual cells, lag is defined as the time required to reach first cell division.

FIG 2

Total number and commonality genes in the lag phase of “young” (1-day-old) and “old” (16-day-old) E. coli cells that were differentially expressed compared to the preceding stationary phase. Diagram produced from data reported by Pin and coworkers (89).

FIG 3

Metabolic and growth trends of bacterial cultures from lag to early stationary phase. Adapted from the work of Yamamotoya and coworkers (90). Exp., exponential phase; OD, optical density; OD(600), OD at 600 nm; Conc., concentration.

FIG 4

An abstraction of the physiological trends in the lag and exponential phases of B. cereus. Adapted from the work of Biesta-Peters and coworkers (91).

FIG 5

Physiological trends in protein synthesis (A) and respiration (B) in soil-dwelling bacteria. Soil was dried for 4 days or 1 year. The soil was then rewetted and monitored for 125 h. The control culture was incubated in moist soil. Adapted from the work of Meisner and coworkers (93).

FIG 6

Quantification of the intracellular iron concentration (A) and sensitivity to H₂O₂ treatment (represented as fold decrease in viability) (B) during and after a 2-h lag phase in S. enterica. Adapted from the work of Rolfe and coworkers (73). Inoc., inoculation.

FIG 7

(A) Activating and repressing elements determining the concentration of FtsZ and the triggering of first cell division at the end of lag phase. (B) Abstraction of the concentration of FtsZ during the stationary phase, lag phase, and first cell division. Adapted from the work of Sekar and coworkers (124).