Lecture 14:

Microbial Rhythms and Circadian Interactions

Understanding the relationship between microbial activity and circadian rhythms is crucial in comprehending how organisms, from prokaryotes to mammals, adapt and function in a cyclic world. This article synthesizes various perspectives on microbial rhythms, circadian clocks in different organisms, and the intricate interactions between host and microbiome circadian rhythms.

Overview of Circadian Rhythms

Definitions and Purpose

• Biological Rhythms: Regularly recurring fluctuations in biological processes.

• Circadian Rhythms: Cycles that last approximately 24 hours and are endogenously generated (self-sustaining). Examples include body temperature, alertness, and hormone levels.

Circadian rhythms help organisms anticipate daily environmental changes, allowing them to allocate physiological processes proactively rather than reactively.

Core Concepts in Circadian Biology

• Entrainment: Synchronization of an organism's internal clock to external environmental cues, primarily light.

• Free-Running: The internal clock operating without external cues.

• Zeitgeber: External signals like light that synchronize the circadian clock.

• Period (Tau): Time for one complete cycle of a rhythm.

• Amplitude: Difference between peak and mean levels of a rhythmic output.

Historical Insights

The foundations of circadian biology were laid by researchers who identified and characterized the dependencies and cycles of rhythmic proteins, such as PER, in organisms like Drosophila (fruit flies).

Microbial Rhythms

Cyanobacteria: A Model for Microbial Clocks

Cyanobacteria, specifically Synechococcus elongatus, were the first prokaryotes where a circadian clock was identified. Their clock consists of three proteins (KaiA, KaiB, and KaiC) that undergo phosphorylation cycles, thus regulating gene expression in a rhythmic manner. Approximately 30% of their genome is under circadian control, and their clock can entrain to light and metabolic cues.

Rhythm in Non-Photosynthetic Bacteria

Research has shown that non-photosynthetic bacteria like E. coli and Klebsiella species exhibit rhythmic behaviors when subjected to cyclic environmental conditions. For instance:

• E. coli grown in a spiral tube under constant conditions exhibited a rhythm but lost it after a few days.

• Klebsiella pneumoniae and Klebsiella aerogenes displayed rhythmic patterns in bioreactors but lacked free-running rhythms under constant conditions.

These findings suggest that while some bacteria exhibit rhythms, their mechanisms and persistence differ from classic circadian rhythms.

Metabolic and Diurnal Adaptations of Vibrio fischeri

Vibrio fischeri, a bioluminescent bacterium, exhibits substrate-specific metabolic efficiency:

• Fermentative growth yields higher energy with GlcNAc under anaerobic conditions.

• Anaerobic respiration with glycerol yields more energy when electron acceptors are unavailable.

Host-Microbe Circadian Interactions

Symbiotic Relationships: The Hawaiian Bobtail Squid

The Hawaiian bobtail squid and Vibrio fischeri showcase a mutualistic relationship with tight circadian regulation characterized by:

• Light Organ Development: Initially arrhythmic, becomes nocturnal within four weeks as symbiosis matures.

• Diel Metabolism: V. fischeri switches between glycerol phosphate respiration by day and chitin fermentation by night, optimizing light production for the squid.

Microbiota and Host Circadian Clock

Gut microbiota also exhibit circadian rhythms influenced by the host's clock and external cues like feeding schedules. Research in mice models and other organisms indicates:

• Disruption in the host circadian clock (e.g., through shift work or jet lag) alters microbial composition and rhythmicity.

• Microbial rhythms impact metabolic processes, nutrient absorption, and immune responses.

Melatonin and Microbial Rhythms

Melatonin, primarily secreted by the pineal gland, regulates sleep and circadian rhythms:

• It influences bacterial behaviors, as seen in Klebsiella aerogenes, which exhibits cyclic patterns in response to melatonin in vitro.

• Robust melatonin rhythms correspond with microbial rhythms in ruminants, illustrating the systemic impact of hormonal cycles.

Conclusion

Microbial rhythms and their interaction with host circadian systems reveal the complexity and adaptability of life forms to cyclic environments. Further research is essential to explore how these intricate relationships impact health and disease, offering insights into the broader implications of circadian biology.