Tag: Group A Streptococcus

Categories : Diseases, Syndromes and ConditionsTags :

Research Shines a Light on Emerging Virulent Streptococcus Subspecies

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This illustration depicts a 3D computer-generated image of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Credit: CDC on Unsplash

A concerning increase in global rates of severe invasive infections becoming resistant to key antibiotics has a team of infectious disease researchers at the Houston Methodist Research Institute studying a recently emerged strain of bacteria, Streptococcus dysgalactiae subspecies equisimilis (SDSE). SDSE infects humans via the skin, throat, gastrointestinal tract and female genital tract to cause infections ranging in severity from pharyngitis to necrotising fasciitis. The findings of this study are described in a paper appearing in the journal mBio. 

Though closely related to group A streptococcus (also commonly known as Streptococcus pyogenes), which has been very well studied, little is known about SDSE.

“Given its great emerging importance to human health, our limited understanding of SDSE molecular pathogenesis is remarkable,” said Jesus M. Eraso, PhD, an assistant research professor of pathology & genomic medicine with Houston Methodist and lead author on the study.

To close this knowledge gap, the Houston Methodist team used a sophisticated integrative approach to study 120 human isolates of a particular SDSE subtype, called stG62647. They analysed the subtype’s genome, where the information of its DNA is stored, its transcriptome, which provides a snapshot of the complete gene expression profile at the time the SDSE cells were collected, and its virulence, which refers to the degree of damage it causes to its host. The stG62647 SDSE strains are important to study because they have been reported to cause unusually severe infections, and understanding the relationships and interplay between these three entities gave the researchers a richer understanding of how it causes disease.

The data from this integrative analysis provided much new data about this important emerging human bacterial pathogen and are useful in vaccine research. It also raised many new questions and generated new hypotheses to be studied in this ongoing line of investigation.

Source: Houston Methodist Research Institute

Categories : Diseases, Syndromes and ConditionsTags :

Strep A Toxin Serves as Both Weapon and Shield

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Streptococcus pyrogenese bound to human neutrophil
Streptococcus pyogenese bound to a human neutrophil. Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

Griffith University researchers have unlocked one of the secrets as to why some forms of Streptococcus Group A (Strep A) are associated with severe invasive infection. The results, published in mBio, suggest that a toxin it secretes not only damages cells but helps Strep A resist host defence.

Around the world, invasive Strep A diseases are responsible for more than 163 000 deaths annually and a recent increase in cases of invasive Strep A disease has been observed internationally.

For the past 10 years, Institute for Glycomics Associate Professor Manisha Pandey and Professor Michael Good have been researching the pathways in which Strep A can spread through the body.

“The findings from this study will have far-reaching implications as Strep A is responsible for a significant number of invasive and non-invasive infections which cause significant morbidity and mortality globally,” Associate Professor Pandey said.

“The reason for this is that invasive organisms express significantly more of the toxin, streptolysin O (SLO), which was the main focus of this study.

“SLO exerts potent cell and tissue destructive activity and promotes Strep A resistance to clearance by white cells in the body which is the critical first element of host defence against invasive Strep A infection.”

Professor Good said: “We found SLO alters interactions with host cell populations and increases Strep A viability at sites in the body such as the blood and spleen, and that its absence results in significantly less virulence.”

“Essentially, the less SLO present, the less severe the case of Strep A.”

SLO is secreted by nearly all Strep A isolates, but those that secrete the most SLO are the most virulent.

This work underscores the importance of SLO in Strep A virulence while highlighting the complex nature of Strep A pathogenesis.

This improved insight into host-pathogen interactions will enable a better understanding of host immune evasion mechanisms and inform streptococcal vaccine development programs.

Dr Pandey said a key finding was the presence of SLO in invasive organisms did not impair the ability of the Strep A vaccine candidate developed by Griffith University’s Institute for Glycomics and which is now in a clinical trial.

The Strep A virulence study was part of a PhD project undertaken by Dr Emma Langshaw.

Source: Griffith University

Categories : VaccinesTags :

Antibody Discovery Suggests a Possible New Vaccine for Strep A

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Streptococcus pyrogenese bound to human neutrophil
Streptococcus pyogenese bound to a human neutrophil. Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

Researchers at Lund University in Sweden have discovered an antibody that could potentially protect against Strep A infection, as well as a rare form of antibody binding, that leads to an effective immune response against bacteria. The discovery could explain why so many Group A strep vaccines have failed.

The results are published in EMBO Molecular Medicine.

Group A streptococci have several ways in which they evade the body’s immune system and, when they infect us, can cause both common throat infections (strep throat), scarlet fever, sepsis, swine pox and skin infections. So far, antibiotics work against these bacteria, but should they become resistant, they will pose a major public health threat.

One strategy that the scientific community uses to find new ways of fighting bacterial infections is to create target-seeking antibodies. First, the antibodies that the body’s immune system produces in the event of an infection are mapped, and then their effect on the immune system is studied. In this way, antibodies can be identified that can be used both for preventive treatment and for treatment during an ongoing infection. It is a difficult process, though, with many attempts to develop antibody-based treatments against Strep A ending in failure.

The current study shows an unexpected way that antibodies interact with group A streptococci and, more specifically, how they hook onto the probably most important bacterial protein, the M protein, on the cell surface.

“We found that it happens in a way that has never been described before. Normally, an antibody binds via one of its two Y arms to its target protein at a single site, regardless of which of the two arms is used for binding. But what we have seen- and this is vital information – is that the two Y arms can recognise and hook on to two different places on the same target protein,” explains study author Pontus Nordenfelt.

This means that the two arms of the antibody – which are identical – can bind to two different sites on a target protein. It turns out that it is precisely this type of binding that is required for effective protection, and since it is probably rare, the researchers believe, it could explain why so many vaccine attempts have been unsuccessful. It could also be a reason why the bacteria manage to escape the immune system.

It has long been known that the streptococcal bacteria’s M protein is of great importance for how disease occurs and develops in the body. Finding an antibody that attaches to this protein, thereby flagging it up to the immune system, can prevent the bacteria from infecting the body’s cells. Since we know that the human body can fight the infection, such antibodies exist, but it is hard to locate them.

The researchers therefore focused on examining antibodies in patients who had recovered from group A streptococcal infection. They managed to identify three so-called monoclonal antibodies from a patient who recovered from a Strep A infection. Monoclonal antibodies are identical copies of each other, and in this case target a single protein (the M protein) of the group A streptococci. The researchers then investigated in animal studies whether it is possible to use the antibodies to strengthen the immune system in its fight against group A streptococcus. It turned out that the antibody with the newly discovered binding mechanism produced a strong immune response against the bacteria. The researchers have now applied for a patent based on the findings in the article, and will continue to study the antibody.

“This opens up possibilities where previous vaccine attempts have failed and means that the monoclonal antibody we used has the potential to protect against infection,” concludes study author Wael Bahnan.

Source: Lund University