Fat Bacteria? Skinny Bacteria? There’s a Reason Microbes Stay in Shape

Rice University theorists show how random processes cancel out to ensure microbial health.

Fat bacteria? Skinny bacteria? From our perspective on high, they all seem to be about the same size. In fact, they are.

Precisely why has been an open question, according to Rice University chemist Anatoly Kolomeisky, who now has a theory.

A primal mechanism in bacteria that keeps them in their personal Goldilocks zones — that is, just right — appears to depend on two random means of regulation, growth and division, that cancel each other out. The same mechanism may give researchers a new perspective on disease, including cancer.

The “minimal model” by Kolomeisky, Rice postdoctoral researcher and lead author Hamid Teimouri and Rupsha Mukherjee, a former research assistant at Rice now at the Indian Institute of Technology Gandhinagar, appears in the American Chemical Society’s Journal of Physical Chemistry Letters.

A simple theoretical model by Rice University scientists seeks to explain why bacteria remain roughly the same size and shape. The model shows the random processes of growth and division are linked, essentially canceling each other out. Credit: Kolomeisky Research Group/Rice University

“Everywhere we see bacteria, they more or less have the same sizes and shapes,” Kolomeisky said. “It’s the same for the cells in our tissues. This is a signature of homeostasis, where a system tries to have physiological parameters that are almost the same, like body temperature or our blood pressure or the sugar level in our blood.

“Nature likes to have these parameters in a very narrow range so that living systems can work the most efficiently,” he said. “Deviations from these parameters are a signature of disease.”

Bacteria are models of homeostasis, sticking to a narrow distribution of sizes and shape. “But the explanations we have so far are not good,” Kolomeisky said. “As we know, science does not like magic. But something like magic — thresholds — is proposed to explain it.”

For bacteria, he said, there is no threshold. “Essentially, there’s no need for one,” he said. “There are a lot of underlying biochemical processes, but they can be roughly divided into two stochastic chemical processes: growth and division. Both are random, so our problem was to explain why these random phenomenon lead to a very deterministic outcome.”

The Rice lab specializes in theoretical modeling that explains biological phenomena including genome editing, antibiotic resistance, and cancer proliferation. Teimouri said the highly efficient chemical coupling between growth and division in bacteria was far easier to model.

“We assumed that, at typical proliferation conditions, the number of division and growth protein precursors are always proportional to the cell size,” he said.

The model predicts when bacteria will divide, allowing them to optimize their function. The researchers said it agrees nicely with experimental observations and noted manipulating the formula to knock bacteria out of homeostasis proved their point. Increasing the theoretical length of post-division bacteria, they said, simply leads to faster rates of division, keeping their sizes in check.

“For short lengths, growth dominates, again keeping the bacteria to the right size,” Kolomeisky said.

The same theory doesn’t necessarily apply to larger organisms, he said. “We know that in humans, there are many other biochemical pathways that might regulate homeostasis, so the problem is more complex.”

However, the work may give researchers new perspective on the proliferation of diseased cells and the mechanism that forces, for instance, cancer cells to take on different shapes and sizes.

“One of the ways to determine cancer is to see a deviation from the norm,” Kolomeisky said. “Is there a mutation that leads to faster growth or faster division of cells? This mechanism that helps maintain the sizes and shapes of bacteria may help us understand what’s happening there as well.”

Reference: “Stochastic Mechanisms of Cell-Size Regulation in Bacteria” by Hamid Teimouri, Rupsha Mukherjee and Anatoly B. Kolomeisky, 1 October 2020, Journal of Physical Chemistry Letters.
DOI: 10.1021/acs.jpclett.0c02627

Kolomeisky is a professor of chemistry and of chemical and biomolecular engineering. The Welch Foundation, the National Science Foundation and Rice’s Center for Theoretical Biological Physics supported the research.

BacteriaBiochemistryCell BiologyMicrobiologyRice University
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  • Sekar Vedaraman

    Very Interesting.

    Read this interesting article earlier about the sex ratio in recent birhswhich have become skewed in liberal Nations like Canada whereas the ratio of males to female birth remains unskewed in the conservative heartlnd in USA

    Have been trying to figure out why the sex ratio gets disturbed in the current unceratin times where many more female births are taking place in Canada and other liberal Nations. Maybe, the above findings and theory being proposed can be extended to complex systems like humans and the start of the answer related to Nature responding to the perceived threats to humanity to increase female birth who can be less susceptible to Covid as comapred to the male.

    Big stretch , but maybe theory needs to come prior to the experimental findings based on real chemistry and biology. Statistical probabilities and corelations are interesting but needs to be tempered with outliers which are more important from a scientific persective.

    • Torbjörn Larsson

      Sex ratio is different than stochasticity and homeostasis, so [too] “big stretch”. It is decided by the genetics behind biological sex (which is observed in gametes, typically binary: a larger female and a smaller male cell type). Typically chromosome sorting decides the sex in mammals and comes out as a 50:50 ratio with little if any skew. The evolved system in humans is based on combinations of X and Y chromosomes (as well as random deactivation of an X chromosome in XX females to ensure correct gene product rates).

      I don’t know about any article showing a correlation with national politics across the ideological liberal-conservative scale (and you don’t give a link). If anything the expected outcome would be the converse of what you describe, with conservative societies trying to control sex practices and outcome. In the real world of statistics and outliers the result may confirm this (but diseases is not affecting it visibly):

      “The ratio between the number of males and females in a society is referred to as the gender ratio [they mean sex ratio]. This ratio is not stable but instead shaped by biological, social, technological, cultural, and economic forces. And in turn the gender ratio itself has an impact on society, demography, and the economy.”

      “The sex ratio at birth is not equal: in every country births are male-biased. There are biological reasons why there are slightly more boys born every year than girls. The ‘natural’ sex ratio at birth is around 105 boys per 100 girls (ranging from around 103 to 107 boys).

      In some countries, the sex ratio at birth is much more skewed than would occur naturally. Today and in the recent past this is particularly common across Asia and North Africa. Here there is clear evidence of gender selection through prenatal sex determination and selective abortion.”

      “The sex ratio tends to decrease over the life course (from becoming male-biased to female-biased). This is because women tend to live longer than men.”

      The map “Share of the population that is female, 2017” shows the global pattern of 50:50 ratio.

      “Most countries have a female share of the population between 49 and 51 percent (within one percentage point of parity).

      There are however a few notable outliers:
      -across several countries in South and East Asia – most notably India and China – there are significantly fewer females than males. These are countries where there are large differences in sex ratio at birth.
      – in several countries across the Middle East there are many more males than females: in Oman, women are outnumbered 3-to-1; in the United Arab Emirates (UAE) it’s almost 4-to-1. … The primary reason for this is a large male migrant stock …
      – there are significantly more females than males in Eastern Europe. Populations in Eastern Europe have some of the largest gaps in life expectancy between men and women: in Russia, for example, the average life expectancy at birth was only 65 years compared to 76 years for women.”

      [ https://ourworldindata.org/gender-ratio ]

      • Torbjörn Larsson

        I meant to note that inactivation of an X in XX females leaving an active X_a is stochastic at a rather late stage (gastrulation – so human females are X_a chimeric).

  • Torbjörn Larsson

    Mildly interesting that a stochastic balance translates to a homeostatic solution. They don’t discuss the homeostasis cell size factors.