Research in Brief: The What, Why, and How


In Research In Brief: The What, Why, and How, we explore new research from the UW–Madison Department of Biochemistry to learn more about the world around us — and inside us. In this edition: Diversity is the key to survival for the beneficial bacteria living in your gut microbiome. Now, scientists have new ways to explore the wide genetic diversity within a species of bacteria essential to human gut health.

WHAT you need to know

Your gut is a constantly shifting ecosystem. Everything you do — what you eat, how much you exercise, the air you breathe, the medications you take — can impact the environment of the trillions of microbes that call you their home. An illness, change in diet, or antibiotics can all affect beneficial bacteria living in your gut microbiome.

Diversity is key to survival for these single-celled organisms. Within a single species of bacteria, some individuals may be very good at finding food when resources are scarce, while others may be more likely to survive an attack by bacteriophages (viruses that attack bacteria). Through diversity, bacteria can hedge against environmental stressors and increase the chances that the population will survive.

Bacteria have evolved with mechanisms to increase diversity across a species. Some species of bacteria maintain genetic diversity by employing reversible changes which alter the architecture of their cell surface, or shell. One of the ways these changes are controlled is through a series of on/off switches called “promoters.” If a promoter is turned on, the bacterium can produce a protein that will impact the cell surface; if the promoter is turned off, it cannot produce the protein. Bacteria have multiple promoters that can be turned on and off in different combinations.

WHY it matters

This kind of diversity determines how the bacteria interact with each other and with their environment. Thanks to variability in cell surfaces, some bacteria may be impermeable to antibiotics, immune to bacteriophages, unresponsive to host immune system responses, or more inclined to interact with their neighbors. Cell surface diversity allows bacteria to diversify their arsenal, enabling populations of bacteria to survive in changing environments. It also impacts fitness — the ability of individuals to survive adverse environmental conditions and pass on their genes to the next generation.

Until recently, it has not been possible to study promoter orientation in large numbers of individual bacteria. Researchers have only been able to study populations of bacteria and estimate the ratios of promoters turned on or off. This has limited their ability to explore whether specific combinations of promoters hold key opportunities for therapeutic treatments by enabling more targeted uses of antibiotics and bacteriophages.

HOW our scientists made progress

Researchers in the Landick and Venturelli labs have, for the first time, been able to explore the genetic diversity by examining promoter orientation among individuals within a population of Bacteroides fragilis, a species of bacteria essential to human gut health. Their findings have been published in Science Advances.

Diversity in cell surface structure increases over time in populations of Bacteroides fragilis
This time lapse depicts a population of B. fragilis which begins at time 0 as a population with a single cell surface architecture. Over a 24-hour period, the diversity of cell surface architecture in the population increases.

By developing new techniques that allow researchers to isolate and examine a large number of individual cells, the scientists were able to sequence parts of the genome of tens of thousands of B. fragilis cells and identify which promoters were on and which were off in each cell. They also tracked changes in which promoters were on and off in individual cells over time. The composition of promoter orientations within a population at any given moment is, in part, a reflection of environmental pressures.

This method is now starting to give scientists a glimpse into the biochemical mechanisms responsible for turning promoters on and off, and opens the door to new avenues of research. Researchers will also be able to track how a population responds to environmental stressors and can ask specific questions about how bacteria in the gut microbiome respond to everyday health concerns such as inflammation, competition with pathogenic bacteria, and exposure to antibiotics.

This information plays an essential role in identifying how to support and maintain the bacteria crucial to our health. By learning more about the diversity that sustains the gut microbiome, we learn more about how and why the human gut responds to normal fluctuations in our daily lives — such as an increase in stress or a course of antibiotics — as well as larger environmental shifts, such as air and water quality.

Written by Renata Solan.


This edition of Research in Brief: The What, Why, and How is based on the following publication:

Freeman, L., Saba, J., Qian, Y., Ross, T., Landick, R., Venturelli, O. Single-cell analysis of multiple invertible promoters reveals differential inversion rates as a strong determinant of bacterial population heterogeneity, Sci. Adv., 2023 Aug 4, 9(31).

Financial support for this work was provided by the National Institutes of Health (T32 GM135066, T32 GM008349, F31 GM142153, R35 GM124774, R35 GM12477409, R21 AI156438), the Army Research Office (W911NF-19-1-0269), the Burroughs Wellcome Fund, WARF, and UW–Madison.