#FEMSmicroBlog: Pathogenic streptococci exploiting human sugars

09-04-2022

Group A Streptococcus (also known as GAS) is a bacterium that is responsible for hundreds of thousands of deaths each year. Like many organisms on Earth, GAS requires carbohydrates to survive. However, human carbohydrates aren’t just a nutrition source for this species – they are targets of many bacterial pathways important in causing disease. The article “The exploitation of human glycans by Group A Streptococcus”, published in FEMS Microbiology Reviews, outlines the roles of host glycans in GAS disease. Anuk Indraratna explains for #FEMSmicroBlog how GAS targets sugars during the infection process. #FascinatingMicrobes

 

What is Group A Streptococcal disease?

Group A Streptococcus (GAS) causes millions of infections each year around the world. Most of the time, GAS disease presents superficially as a throat or skin infection. Sometimes, however, it is more severe, causing flesh-eating skin infections or severe and potentially fatal auto-immune diseases like rheumatic heart disease.

A growing body of evidence suggests that human carbohydrates (also known as glycans) are involved in several different aspects of GAS infection. For example, GAS targets human glycans when neutralising immune proteins, bursting red blood cells and attaching to the human throat.

The review “The exploitation of human glycans by Group A Streptococcus” in FEMS Microbiology Reviews examines the diverse ways in which GAS exploits host glycans to survive, thrive and cause disease within the human body. Specifially, it outlines the roles of host glycans on bacterial adherence, carbohydrate metabolism, evasion of immunity, biofilm adaptations and toxin-mediated haemolysis.

 

Are glycans important in immunity to infection?

Glycans – also referred to as carbohydrates or sugars – aren’t just in our diet; they exist in thousands of forms throughout the human body and have many important roles. One example is the tiny sugar on the surface of blood cells that determines blood type, with devastating consequences if not accounted for during transfusions.

At least half of all human proteins contain glycans which modify their structure, cellular location or function in some crucial manner. For example, immunoglobulin G (IgG), a circulating, pathogen-fighting antibody is a protein with several small glycans attached.

Streptococci cleaves human IgG to overcome the immune system.
GAS modifies IgG.

Interestingly, GAS has a glycan-degrading enzyme that strips glycans off the antibody leaving the protein structure intact. However, without its glycans this critical weapon of the anti-infection arsenal is far less potent. This is just one known example of GAS targeting human glycans and many more are yet to be fully understood.

 

Cell-killing toxins target human glycans

As mentioned earlier, glycans cover the surface of red blood cells. During severe GAS disease, when the infection has reached the bloodstream, these sugars are targeted by a GAS toxin, Streptolysin O.

Streptolysin O plays many roles in GAS infection Yet, it is best known for its ability to form deadly pores in target cells. This attack forces the content to leak out followed by bacterial molecules infiltrating.

When Streptolysin O comes into contact with a blood cell, it first attaches to a galactose sugar. Additional Streptolysin O molecules attach to the same galactose forming a much larger complex or polymer. The fully formed Streptolysin O polymer then attaches to cholesterol on the cell membrane and embeds itself into the cell.

Streptococci produces streptolysin to bind to human glycans and sugars on the cell surface.
Streptolysin produces pores in cell membranes. From Indraratna et al. (2022).

However, in some instances, where there’s no galactose, some other (yet to be identified) glycan is targeted during Streptolysin O assembly. Here, Streptolysin O recruits another toxin, SPN, which binds to this non-galactose glycan. This recruitment then allows Streptolysin O to assemble into its cell-killing polymeric form.

 

Glycans in the throat

The human throat (or pharynx), where GAS mainly causes infections, is rich in glycans. While many of these have anti-microbial properties, other glycans are instead targeted by pathogens.

GAS possesses many proteins at its surface that recognise and bind to these glycans, strengthening the bacterium’s ability to attach to the epithelial layer of the throat. Some studies have shown that blocking these glycan-protein interactions can reduce bacterial attachment to human cells.

Like many bacterial and viral pathogens, GAS interacts with and exploits host carbohydrates to survive and cause disease within the human body. Ongoing research will continue to uncover just how crucial these interactions are and may even lead to novel, glycan-based therapies.

 

About the authors of this blog

Professor Danielle Skropeta leads a research group at the University of Wollongong in chemical glycobiology, which holds the key to better treatments in cancer and microbial infections. Originally from Melbourne, Danielle completed her PhD in chemistry at the Australian National University (1999), followed by fellowships in Italy and Germany. Currently Associate Dean (Higher Degree Research), Danielle is a Fellow and Board Member of the Royal Australian Chemical Institute (RACI, 2019), Senior Fellow of Advance HE (Higher Education UK, 2019) and recipient of the RACI Margaret Sheil Leadership Award (2021). Danielle is passionate about sharing science from podcasts, radio interviews and TV documentaries, to science shows and museum exhibits. Danielle works in collaboration with industry, community and government and strives to create a more welcoming and inclusive STEM environment for all. In 2021, she joined Homeward Bound’s leadership program to increase the impact and influence of women in STEM to help shape the future of our planet.

Anuk Indraratna is a PhD candidate at the University of Wollongong in the Molecular Microbiology Research Group, led by A/Prof. Martina Sanderson-Smith. He is interested in improving the understanding, diagnosis, and treatment of infectious disease, and is currently researching the involvement of human glycans in Group A Streptococcal infection. Anuk is a keen science communicator and is passionate about scientific literacy in the community. He is involved in a number of initiatives to engage and educate public audiences with the impactful research that local scientists are undertaking.

Associate Professor Martina Sanderson-Smith is a molecular bacteriologist leading a research team at the University of Wollongong (UOW). Martina leads a research team investigating virulence mechanisms of the human pathogen Streptococcus pyogenes, with specific interests in interactions between S. pyogenes and the host fibrinolytic system, the role of host glycans in bacterial infection, mechanisms of innate immune resistance, host susceptibility to infection and biofilm formation. Martina also teaches Microbiology, Molecular Biology, Biochemistry and Immunology at UOW and supervises undergraduate and postgraduate research students. Martina is a strong advocate for the embedding of principles of Equity, Diversity and Inclusion in teaching, research practice and training.

About this blog section

The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.

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