Who Moved My Genes, Horizontally, on My Cheese?

These are representative colonies of bacteria from cheese analyzed in the study growing on a petri dish. [Rachel Dutton/UCSD]

The fiercest rat races may be found in microbiomes, communities of microorganisms that are subject to brutal selective forces—environmental fluctuations, toxic chemicals, and nutrient-poor conditions. While it’s easy to imagine how rats might cope with desperate circumstances, such as dwindling cheese stores, micoorganisms are rather more mysterious. It is necessary for us to find some way to model microbiomes if we are to understand how they respond to changing circumstances and overcome adversity.

If we had better models, not only might we advance basic research, we might also achieve practical goals. For example, we might find ways to interfere with the community-level behaviors among microbes that give rise to antibiotic resistance.

Better models are being developed by scientists based at the University of California, San Diego. Conveniently enough, these models make use of artisanal cheeses. What’s more, by using these models, the scientists have found that microbial species living on cheese may transfer thousands of genes between each other. They also identified regional genomic hotspots where gene exchanges are especially marked, including several genomic “islands” that host exchanges across several species of bacteria.

Details of this work appeared July 25 in the journal eLife, in an article entitled “Extensive Horizontal Gene Transfer in Cheese-Associated Bacteria.” The article describes how cheese rinds offer a novel way to study how genes in microbial communities are passed from one organism to another.

“Comparing 31 newly sequenced and 134 previously sequenced bacterial isolates from cheese rinds, we identified over 200 putative horizontally transferred genomic regions containing 4733 protein coding genes,” wrote the article’s authors. “The largest of these regions are enriched for genes involved in siderophore acquisition, and are widely distributed in cheese rinds in both Europe and the US.”

Graphic depiction of horizontal gene transfer analyzed in sample cheese bacteria, with the level of connection depicted through thickness of lines. [Rachel Dutton/UCSD]

The article notes that horizontal gene transfer has been studied for almost 100 years, but added that examining this mechanism directly is still a challenge. Almost by definition, horizontal gene transfer requires studying a community of microbes rather than one microbe in isolation.

To meet this challenge, the UCSD team, which was led by Rachel Dutton, Ph.D., turned to the outer surface of cheese, also known as cheese rind. As a model system, the cheese rind microbiome is relatively simple to work with because cheese rind is easy to replicate in the laboratory and the microbes growing on cheese can be grown on their own or in combinations with other microbes.

The UCSD team observed that a large percentage of transferred genes were involved in functions dealing with acquiring nutrients, especially iron, which is known to be scarce on the surface of cheese. Competition for iron is an important theme for microbes in many environments, including during infections of humans by pathogenic microbes.

“Horizontal gene transfer could influence competition for iron and possibly enable 'cheating' within a mixed community,” commented Dr. Dutton.

Based on the new results, Dr. Dutton and her colleagues are now probing the intricate dynamics of horizontal gene transfer and how the process unfolds on cheese.

“Since horizontal gene transfer is prevalent in many microbial communities, including those important for human health,” insisted Dr. Dutton, “we're now trying to study how this process impacts microbial life and death in a community.”