After taking a course of antibiotics, often the commensal gut microbiome is wiped out. This allows vancomycin-resistant Enterococci to proliferate in the human gastrointestinal tract. As these reach the blood, difficult and often deadly septicemia can follow. The study “The role of the universal sugar transport system components PtsI (EI) and PtsH (HPr) in Enterococcus faecium” aimed to identify novel targets to prevent blood infections, as explained by Michelle Hallenbeck in this #FEMSmicroBlog interview. #TheCulturePlate

 

Can you summarise the significance of your paper for microbiologists outside of your field?

Enterococcus faecium is responsible for the majority of blood infections. Due to its intrinsic and acquired multidrug resistance, we currently have only limited treatment options. That’s why we set out to identify alternative mechanisms to reduce enterococcal populations in the gut.

In many bacterial species, the phosphotransferase system does not only play a crucial role in sugar uptake but also in metabolism. As a start, we investigated PtsH and PtsI. In Enterococcus faecium, both these proteins are involved in phosphorylating the phosphotransferase system transporters as well as in competitive fitness and biofilm formation.

We showed that disrupting these processes reduces enterococcal growth and persistence in the gut. Since this reduces the likelihood of translocation into the bloodstream, inhibiting individual phosphotransferase system transporters with sugar analogs may be a promising strategy.

 

What can policy makers learn from your research results?

Vancomycin-resistant Enterococci have been declared a serious health threat by the Centers for Disease Control and Prevention (CDC), as tens of thousands of cases occur every year, incurring thousands of deaths and hundreds of millions of dollars in healthcare costs. Hospitalized patients, particularly those undergoing antibiotic treatment, are at high risk of being colonized by vancomycin-resistant Enterococci and developing invasive blood infections.

The rising sugar consumption in the Western diet is indeed linked to sugar transport and metabolism genes in Enterococcus faecium. We hypothesize that vancomycin-resistant Enterococci has evolved to take advantage of the increased sugar availability. Therefore, lower levels of sugar consumption would be highly recommended to alleviate the threat posed by vancomycin-resistant Enterococci.

Another goal would be to target specific sugar transporters or sugar metabolism pathways that give vancomycin-resistant Enterococci its competitive advantage. Further research into its sugar metabolism and how it affects survival and colonization is important to identify and develop additional therapeutic targets.

 

What was one of the main hurdles you encountered, and how did you solve it?

One challenge I faced during this study was to compensate for the different growth rates of our wild-type Enterococcus faecium and the ΔptsHI mutant during the in vitro competitive fitness assay. The mutant has an inherent growth defect due to its inability to take up and metabolize certain sugars.

Under normal shaking conditions, the wild-type strain grows quickly and starts to die off after reaching a certain point. However, the ΔptsHI mutant starts to grow much later and continues growing even when the wild-type starts dying off.

To ensure both strains have enough viable cells for the experiment, I adjusted the incubation method. I incubated both strains overnight in a larger volume of media without shaking. This slower growth environment allowed the wild-type strain to grow without entering the death phase prematurely. Yet, it gave the ΔptsHI mutant enough time to reach a sufficient growth level for the competitive fitness assay.

 

Why did you choose to dive into the topic of this paper?

The roles of PtsH and PtsI are well understood in many bacterial species. But there has been a knowledge gap regarding their roles in Enterococcus faecium.

Both PtsI and PtsH are involved in numerous processes including biofilm formation, virulence, and several stress responses. Hence, we wanted to know whether and how PtsI and PtsH affect these also in Enterococcus faecium.

I find it incredibly intriguing how one gene and thus protein can have multiple effects and roles in different pathways in addition to its primary role. By deleting or blocking the expression of one gene, several processes can be inhibited or de-repressed. I am fascinated by how this butterfly effect can ripple out in unexpected ways.

 

You decided to opt for the Transparent Peer Review route offered by FEMS Microbes. What motivated you to do so, and what are the benefits in your opinion?

Transparency and access to data are vital for science. Open peer review comes with some risks, especially to early career scientists, but overall the benefits outweigh those risks.

 

• Read the article “The role of the universal sugar transport system components PtsI (EI) and PtsH (HPr) in Enterococcus faecium” by Hallenbeck et al. in FEMS Microbes (2024).

 

About the author of this blog

Michelle Hallenbeck is a PhD candidate at the University of Louisville. She works in the lab of Dr. James Collins studying how sugar metabolism enhances the proliferation of vancomycin-resistant Enterococcus faecium. Her current research focuses on developing bioreactor and wax moth larvae models to characterize mutants in several key sugar metabolism genes. When not in the lab, she enjoys reading, writing, and spending time with her leopard gecko, Samantha.

 

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