Cell Differentiation and Starvation

Activation of Starvation by Survival Genes

Stringent response is a stress response that occurs in bacteria and plant chloroplasts in reaction to stress conditions.

Learning Objectives

Discuss how starvation activates survival genes

Key Takeaways

Key Points

  • The stringent response is signaled by the alarmone (p)ppGpp.
  • In Escherichia coli (p)ppGpp, production is mediated by the ribosomal protein L11 and the ribosome-associated protein RelA with the A-site bound deacylated tRNA being the ultimate inducer.
  • In other bacteria, stringent response is mediated by a variety of RelA/SpoT Homologue (RSH) proteins, some of which activate synthetically, hydrolytically, or both (Rel).

Key Terms

  • stringent response: a stress response in bacteria in reaction to amino-acid starvation, fatty acid limitation, and other stress conditions.

Stringent Response, also called stringent control, is a stress response that occurs in bacteria and plant chloroplasts in reaction to amino-acid starvation, fatty acid limitation, iron limitation, heat shock, and other stress conditions. The stringent response is signaled by the alarmone (p)ppGpp and modulating transcription of up to 1/3 of all genes in the cell. This in turn causes the cell to divert resources away from growth and division and toward amino acid synthesis in order to promote survival until nutrient conditions improve.

In Escherichia coli, (p)ppGpp production is mediated by the ribosomal protein L11 and the ribosome-associated protein RelA with the A-site bound deacylated tRNA being the ultimate inducer. RelA converts GTP and ATP into pppGpp by adding the pyrophosphate from ATP onto the 3′ carbon of the ribose in GTP, releasing AMP. pppGpp is converted to ppGpp by the gpp gene product, releasing Pi. ppGpp is converted to GDP by the spoT gene product, releasing pyrophosphate ( PPi ). GDP is converted to GTP by the ndk gene product. Nucleoside triphosphate (NTP) provides the Pi, and is converted to Nucleoside diphosphate (NDP).

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RelA/ SpoT protein homologue: In bacteria stringent response is mediated by a variety of RelA/SpoT Homologue (RSH) proteins.

In other bacteria, stringent response is mediated by a variety of RelA/SpoT Homologue (RSH) proteins. Some of these proteins activate synthetically, hydrolytically, or both (Rel). The disabling of the stringent response by distruption of relA and spoT in Pseudomonas aeruginosa, produced in infectious cells and biofilms characterized by nutrient limitation, causes greater susceptibility to antibiotics.

During the stringent response, (p)ppGpp accumulation affects the resource-consuming cell processes replication, transcription, and translation. (p)ppGpp is thought to bind RNA polymerase and alter the transcriptional profile, decreasing the synthesis of translational machinery (such as rRNA and tRNA), and increasing the transcription of biosynthetic genes. Additionally, the initiation of new rounds of replication is inhibited and the cell cycle arrests until nutrient conditions improve. Translational GTPases involved in protein biosynthesis are also affected by ppGpp, with Initiation Factor 2 (IF2) being the main target.

Oligotrophs

Oligotrophs are characterized by slow growth, low rates of metabolism, and generally low population density.

Learning Objectives

Examine oligotrophs and their adaptation to nutrient poor environments

Key Takeaways

Key Points

  • Oligotrophic environments are of special interest for alternative energy sources and survival strategies upon which life could rely.

Key Terms

  • oligotroph: An organism capable of living in an environment that offers very low levels of nutrients.

An oligotroph is an organism that thrives in an environment that offers very low levels of nutrients. They may be contrasted with copiotrophs, which prefer nutritionally rich environments. Oligotrophs are characterized by slow growth, low rates of metabolism, and generally low population density. Oligotrophic environments include deep oceanic sediments, caves, glacial and polar ice, deep subsurface soil, aquifers, ocean waters, and leached soils. An ecosystem or environment is said to be oligotrophic if it offers little to sustain life. The term is commonly utilized to describe environments of water, ice, air, rock or soil with very low nutrient levels. Oligotrophic environments are of special interest for alternative energy sources and survival strategies upon which life could rely. An example of oligotrophic bacterium are Caulobacter crescentus.

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Extremophiles: These hot springs are an example of harsh environments that some extremophiles can grow in.

Caulobacter crescentus is a Gram-negative, oligotrophic bacterium widely distributed in fresh water lakes and streams. The control circuitry that directs and paces Caulobacter cell cycle progression involves the entire cell operating as an integrated system. The control circuitry monitors the environment and the internal state of the cell, including the cell topology, as it orchestrates activation of cell cycle subsystems and Caulobacter crescentus asymmetric cell division. The proteins of the Caulobacter cell cycle control system and its internal organization are co-conserved across many alphaproteobacteria species, but there are great differences in the regulatory apparatus’ functionality and peripheral connectivity to other cellular subsystems from species to species. The Caulobacter cell cycle control system has been exquisitely optimized by evolutionary selection as a total system for robust operation in the face of internal stochastic noise and environmental uncertainty.

The bacterial cell’s control system has a hierarchical organization. The signaling and the control subsystem interfaces with the environment by means of sensory modules largely located on the cell surface. The genetic network logic responds to signals received from the environment and from internal cell status sensors to adapt the cell to current conditions.

Starvation-Induced Fruiting Bodies

Starvation-induced fruiting bodies can aggregate up to 500 micrometres long and contain approximately 100,000 bacterial cells.

Learning Objectives

Explain starvation induced fruit bodies

Key Takeaways

Key Points

  • In fruiting bodies, the bacteria perform separate tasks; this type of cooperation is a simple type of multicellular organisation.
  • Myxococcus xanthus colonies exist as a self-organized, predatory single- species biofilm called a swarm.
  • The fruiting process is thought to benefit myxobacteria by ensuring that cell growth is resumed with a group (swarm) of myxobacteria, rather than as isolated cells.

Key Terms

  • quorum sensing: A proposed method of communication between bacterial cells by the release and sensing of small diffusible signal molecules.
  • stigmergy: A mechanism of spontaneous, indirect coordination between agents or actions, where the trace left in the environment by an action stimulates the performance of a subsequent action.
  • saprotrophic: Extra-cellular digestion involved in the processing of dead or decayed organic matter

Starvation-Induced Fruiting Bodies

When starved of amino acids, myxobacteria, or slime bacteria, detect surrounding cells in a process known as quorum sensing . Migrating towards each other, they aggregate to form fruiting bodies up to 500 micrometers long containing approximately 100,000 bacterial cells. In these fruiting bodies, the bacteria perform separate tasks; this type of cooperation is a simple type of multicellular organisation. About one in 10 cells migrate to the top of these fruiting bodies and differentiate into a specialized dormant state called myxospore, which is more resistant to drying and other adverse environmental conditions than ordinary cells.

The myxobacteria are a group of bacteria that predominantly live in the soil and feed on insoluble organic substances. The myxobacteria have very large genomes, relative to other bacteria e.g., 9–10 million nucleotides. Sorangium cellulosum has the largest known (as of 2008) bacterial genome, at 13.0 million nucleotides.

Myxobacteria are included among the delta group of proteobacteria, a large taxon of Gram-negative forms. They can move actively by gliding and typically travel in swarms (also known as wolf packs), containing many cells kept together by intercellular molecular signals. Individuals benefit from aggregation as it allows accumulation of extracellular enzymes which are used to digest food that increases feeding efficiency.

Myxobacteria produce a number of biomedically and industrially-useful chemicals, such as antibiotics, and export those chemicals outside of the cell. When nutrients are scarce, myxobacterial cells aggregate into fruiting bodies, a process long-thought to be mediated by chemotaxis but now considered to be a function of a form of contact-mediated signaling. These fruiting bodies can take different shapes and colors, depending on the species.

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Bacteria use cell signaling to communicate: A swarm of M. xanthus is a distributed system: a population of millions of identical entities that communicate among themselves in a non-centralized fashion, thus behaving as a single entity.

Within the fruiting bodies, cells begin as rod-shaped vegetative cells and develop into rounded myxospores with thick cell walls. These myxospores, analogous to spores in other organisms, are more likely to survive until nutrients are more plentiful. The fruiting process is thought to benefit myxobacteria by ensuring that cell growth is resumed with a group (swarm) of myxobacteria, rather than as isolated cells. At a molecular level, initiation of fruiting body development is regulated by Pxr sRNA.

Myxococcus xanthus colonies exist as a self-organized, predatory, saprotrophic, single-species biofilm called a swarm. Myxococcus xanthus, which can be found almost ubiquitously in soil, are thin rod-shaped, gram-negative cells that exhibit self-organizing behavior as a response to environmental cues. The swarm modifies its environment through stigmergy. This behavior facilitates predatory feeding, as the concentration of extracellular digestive enzymes secreted by the bacteria increases.

M. xanthus is a model organism for studying development, the behavior in which starving bacteria self-organize to form fruiting bodies: dome shaped structures of approximately 100,000 cells. These swarms differentiate into metabolically quiescent and environmentally resistant myxospores over the course of several days. During this process of self-organizing, dense ridges of cells move in traveling waves (ripples) that grow and shrink over several hours.

Bacterial Differentiation

Several bacteria alter their morphology in response to the types and concentrations of external compounds.

Learning Objectives

Explain bacterial differentiation to eukaryotic-like sturctures

Key Takeaways

Key Points

  • Bacterial morphology changes help to optimize interactions with cells and the surfaces to which they attach.
  • Oxidative stress, nutrient limitation, DNA damage and antibiotics exposure are some of stress conditions to which bacteria respond, altering their DNA replication and cell division.
  • The most frequent shape alteration may be filamentation triggered by a limitation in the availability of one or more nutrients.

Key Terms

  • cytoskeleton: A cellular structure like a skeleton, contained within the cytoplasm.
  • septum: a partition that separates the cells of a (septated) fungus
  • segrosomes: multiprotein complexes that partition chromosomes/plasmids in bacteria.
  • cell division: a process by which a cell divides into two cells.

Bacterial morphological plasticity refers to evolutionary changes in the shape and size of bacterial cells. As bacteria evolve, morphological changes occur to maintain the consistency of the cell. However, this consistency could be affected in some circumstances (such as environmental stress) and changes in bacterial shape and size. In bacteria, the transformation into filamentous organisms have been recently demonstrated. These are survival strategies that affect the normal physiology of the bacteria in response to factors such as innate immune response, predator sensing, quorum sensing and antimicrobial signs.

Normally, bacteria have different shapes and sizes which include coccus, rod and helical/spiral (among others less common). This forms the basis for their classification. For instance, rod shapes may allow bacteria to attach more readily in environments with shear stress (e.g., in flowing water). Cocci may have access to small pores, creating more attachment sites per cell and hiding themselves from external shear forces. Spiral bacteria combine some of the characteristics of cocci (small footprints) and of filaments (more surface area on which shear forces can act) and the ability to form an unbroken set of cells to build biofilms. Several bacteria alter their morphology in response to the types and concentrations of external compounds. Bacterial morphology changes help to optimize interactions with cells and the surfaces to which they attach. This mechanism has been described in bacteria such as Escherichia coli and Helicobacter pylori.

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Electron micrograph of H. pylori possessing multiple flagella (negative staining): Several bacteria alter their morphology in response to the types and concentrations of external compounds.This has been described in bacteria such as E. coli and H. pylori.

Oxidative stress, nutrient limitation, DNA damage and antibiotics exposure are some stress conditions to which bacteria respond, altering their DNA replication and cell division. Filamentous bacteria have been considered to be over-stressed, sick and dying members of the population. However, the filamentous members of some communities have vital roles in the population’s continued existence, since the filamentous phenotype can confer protection against lethal environments.Filamentous E. coli can be up to 70 µm in length and has been identified as playing an important role in pathogenesis in human cystitis. There are different mechanisms identified in some bacteria that are attributable to the development of filamentous forms.

Nutritional stress can change bacterial morphology. The most frequent shape alteration may be filamentation triggered by a limitation in the availability of one or more nutrients. Since the filament can increase a cell’s uptake–proficiency surface without changing its surface-to-volume ratio appreciably, this may be enough reason for cells to be filament. Moreover, the filamentation benefits bacterial cells attaching to a surface because it increases specific surface area in direct contact with the solid medium. In addition, the filamentation may allow bacterial cells to access nutrients by enhancing the possibility that the filament will be exposed to a nutrient-rich zone and pass compounds to the rest of the cell’s biomass. For example, Actinomyces israelii grows as filamentous rods or branched in the absence of phosphate, cysteine, or glutathione. However, it returns to a regular rod-like morphology when adding back these nutrients.