Streptococcus pyogenes and its Peculiar Relationship with Glucose

By: May Igani ‘22

Streptococcus pyogenes, a bacteria commonly found to be the culprit of a wide range of healthcare problems has recently been discovered to have an interesting relationship with glucose. This bacteria thrives in two familiar environments, low and high glucose environments. This bacteria is very common as it easily spreads and grows, you may have seen it in illnesses like strep throat, rheumatic fever, toxic shock syndrome, and many others. The U.S. sees about 11 million cases of strep throat a year, 500,000 cases of rheumatic fever, and almost 3/100,000 people in the U.S get diagnosed with toxic shock syndrome annually. It is also the cause of many different kinds of skin infections and lesions.

Figure 1: A gram-stain image of S. pyogenes. The picture shows what S. pyogenes bacteria looks like under a microscope!

Figure 2: A simplified diagram of gram-positive and gram-negative bacteria, showing the difference between the two.

An important aspect of S. pyogenes is that it is a gram-positive microbe which means it is not resistant to antibiotics making any infection easily corrected with antibiotics. As shown in Figure 2, gram-positive bacteria have a thick outer layer while gram-negative bacteria have multiple thin layers. Intuitively, we might think that the thin layers in gram-negative bacteria make these kinds of bacteria easier to destroy. However, that is not the case. Gram-negative bacteria have more complex membranes than gram-positive. They hold different kinds of proteins in the thin layers that give the bacteria additional support. Gram-positive bacteria lack these extra defenses which make them easier to kill.

Figure 3: An image showing the difference between gram-positive and gram-negative bacteria membranes.

In 2021, a paper was published looking at how S. pyogenes becomes highly pathogenic on the surface of the skin. The study “Streptococcus pyogenes upregulates arginine catabolism to exert its pathogenesis on the skin surface” specifically looked at arginine catabolism. Arginine is an important amino acid in the Arginine Deiminase (ADI) Pathway. This pathway supplements various bacteria’s energy and resources which in turn helps the bacteria grow and spread.

Typically bacteria need nutrients like sugar and other carbohydrates to grow and divide. This study shows that S. pyogenes has found a way to be virulent when sufficient or high amounts of glucose are not present. When glucose is not at sufficient levels the bacteria uses the ADI pathway to gain more energy and resources to help the infection spread.

Figure 4: These images show us how S. pyogenes has affected the mice's surface skin layer. The photographs show us lesions and infections on the Wt and Wr mice. The microscopy images show us the Wt and Wr mice lost their topmost outer skin layer (the dark purple layer). Their skin should have the dark purple layer we see with the PBS and arcA mice.

In addition to the beautiful microscopy we see in these pictures, this study also tells us a lot about S. pyogenes’ involvement with the skin’s surface layer. The study had 4 categories of mice with different genetic makeups that were put under a low glucose condition. The control group was mice given a phosphate-buffered saline solution (PBS), which does not alter any genes. The experimental mice were a wild type (Wt), revertant type (Wr), and a mutant type where ArcA, an enzyme that catalyzes the ADI pathway was removed (arcA). 3 out of the 4 mice groups had functioning ADI pathways, the arcA mice being the group without. In the figures, we see the surface skin layer of the mice. For the Wt and Wr mice, the skin surface layer is no longer present. The PBS and arcA mice’s surface skin layer stayed intact. The images in the top row of the mice's backs show lesions and infections on the Wt and Wr mice while the PBS and arcA mice are unharmed.

Arginine catabolism is present in the Wt and Wr mice but they are not in the PBS and arcA mice. These images tell us that when arginine catabolism, and therefore the ADI pathway, is functioning properly, S. pyogenes is able to infect the skin layer. The growth of S. pyogenes caused the surface skin to be damaged and no longer intact. When the ADI pathway is not working properly like in the PBS and arcA mice, the skin layer is not affected.

In contrast to these results, the study did an experiment showing what happens to mice in high glucose conditions when S. pyogenes causes an infection. They examined mice with lab-induced diabetes. This experiment had two conditions- one where the mice were non-diabetic (low glucose on their skin surface), and the other where the mice were diabetic (high glucose on their skin surface). We see S. pyogenes cause an infection when glucose is excessively present and arginine deiminase is inhibited. That is because S. pyogenes has enough glucose to aid its virulent efforts so using or needing the ADI pathway is not necessary.

Figure 5: This is a graph used to show the spread of S. pyogenes on non-diabetic (wt mice) and diabetic mice. The y axis is telling us how much the bacteria spread in “colony forming units” (a unit of measurement for organisms in microbiology). Focusing on the pink squares which are showing arcA mice, we see that for both non-diabetic mice and diabetic mice, there was S. pyogenes growth.

This study is a step forward in understanding why and how S. pyogenes are able to cause infections on the skin even when it does not have enough glucose. Knowing that the ADI pathway is a crucial tool used by the bacteria means that there could be new treatment strategies targeting arginine catabolism and blocking it. By doing this, S. pyogenes could potentially be less virulent on the skin and not create as much harm or decrease the length of time the infection lasts.

​​No matter the glucose condition S. pyogenes is under, it finds a way to induce its pathogenicity on the skin. This tells us that S. pyogenes is a nifty and resourceful bacteria which is more than likely why it is responsible for the many numbers of infections. How glucose and the ADI pathway play into the negative actions of S. pyogenes could help scientists and microbiologists come up with different ways to treat, limit or prevent the spread of S. pyogenes on the skin.