Tale of a troubled microbe


Breaking down the microbiology world one bite at a time

Tale of a troubled microbe

What do you call a microbe that cannot synthesize all the necessary metabolites for its survival? Helpless! Troubled! You feel pity.

The microbe will not agree with you. It is far from being helpless. In fact, not only does the microbe succeed in stealing the required metabolites from its surrounding microbial community, but the microbe also increases its tolerance to antimicrobial drugs. How so? Scientists from UK and UAE found evidence that the presence of these dependent bacteria increases metabolic exchange in a microbial community. Active metabolic exchange increases the microbe’s capacity to transport compounds in and out of the cell, including the discharge of antimicrobial drugs. This, in turn, improves the overall drug tolerance of microbes. In other words, they might become antimicrobial resistant. Antimicrobial resistance is a microbe’s ability to tolerate the toxic effects of antimicrobial treatment. 

What is auxotrophy?

Remember the helpless microbe! Such microbes are called auxotrophs. Auxotrophic microbes cannot synthesize one or more necessary metabolites required for their survival. Examples of such metabolites include amino acids, nucleotides and vitamins. By contrast, prototrophic microbes can synthesize all necessary nutrients for their survival. Auxotrophs depend on prototrophs and external supplements for the missing nutrients. 

Microbial communities comprise of both auxotrophs and prototrophs. Such communities are often associated with a host. This means that microbes survive in a habitat provided by another non-microbial living organism such as the human skin or the human gut. But why do auxotrophs prefer host-associated microbial communities? Because the nutrient reservoir of such environments is continuously replenished. These host provided nutrients are, in turn, used by prototrophic microbes to create metabolites, including the ones that are not synthesized by the host-specific environment. This provides a high concentration of a variety of metabolites to auxotrophs for their continued survival.

How does auxotrophic bacteria affect its surroundings?

An auxotrophic bacteria changes the metabolite exchange of the microbial community. What is a metabolic exchange, you will ask now? All microbes depend on different metabolites for their survival. To use these metabolites, microbes have to transport them inside their cell membrane. Subsequently, the microbes also transport some metabolites that are in excess outside their cell membrane. This in-and-out cycle creates a phenomenon called flux; transporting metabolites in creates an influx and transporting metabolites out creates an efflux. This metabolic flux facilitates exchange of nutrients between different microbes. Scientists found that the addition of auxotrophic microbes changes the community metabolic flux by driving the surrounding microbes to transport more metabolites out of their cells. Overall, efflux from all microbes in a community is affected by the addition of an auxotrophic bacteria, but the auxotroph’s own efflux rate changes more than the efflux of prototrophs.

Relationship between auxotroph and prototroph. Image created by author.

How do microbes become tolerant to drugs through auxotrophy? 

Scientists wondered if, in addition to metabolites, can auxotrophy increase the efflux of antimicrobial drugs from cells? Indeed, they were right! Drugs like azole (an antifungal compound) inhibit the growth of fungal cells, by hindering the synthesis of ergosterol. Ergosterol maintains the fungal cell wall integrity. If fungal cells cannot synthesize ergosterol, they would lyse due to the absence of a robust cell wall. To avoid the toxic effects of azole, the microbes must quickly transport it out of their cell. Scientists monitored the drug efflux activity of auxotrophic and prototrophic strains of yeast. They treated individual cultures of auxotrophic or prototrophic yeast with azole and then measured the extracellular levels of the drug. They found that auxotrophs had more extracellular levels of azole than the prototrophs, suggesting that auxotrophs pumped the drug out more efficiently. They also found that auxotrophs grew better compared to prototrophs in presence of azole. Finally, scientists found that, when grown in co-culture, the auxotrophs also improved the overall drug tolerance of a microbial community of both auxotrophs and prototrophs.

What does this mean for the field of microbiology?

The increased tolerance of auxotrophic yeast to antimicrobial drugs indicates that auxotrophy may have a potential role in determining the drug tolerance levels of microbes beyond yeast (like bacteria). Does this mean that auxotrophy contributes to antimicrobial resistance? The answer to this question might be a bit complicated. 

Let’s take two microbes: A and B. A is auxotrophic, B is prototrophic. Having an auxotrophy means that the microbe A cannot survive without supplementation of metabolites provided by microbe B. This means that even if auxotrophic microbe A tolerates a drug, it would die anyway if the microbe B is more susceptible to the drug treatment! These complicated dynamics of the microbial community affect the collective antimicrobial resistance of a community, especially in the context of host-associated communities. For instance, the human gut is a reservoir for such microbial dynamics. It frequently becomes a victim of infection, and antimicrobial resistance is a major barrier to treating such infections. Therefore, it is important to understand the addition of a host factor in microbial dynamics. The study mentioned in this article is one of the many that helps to unravel the microbial mysteries, one step at a time! 

Link to the original post: Yu, J.S.L., Correia-Melo, C., Zorrilla, F. et al. Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance. Nat Microbiol 7, 542–555 (2022).

Featured image: Image created by the author.