Scientists identify a mechanism of epidemic bacterial disease

Group A Streptococcus
A scanning electron microscope image of Group A Streptococcus (orange) during phagocytic interaction with a human neutrophil (blue). Credit: NIAID

Through identification of increased toxin production by epidemic forms of group A streptococcus (the "flesh-eating" bacterium), for the first time scientists are able to pinpoint the molecular events that contribute to large intercontinental epidemics of disease. The study was based on sequencing almost 5,000 group A streptococcus genomes collected over decades.

Researchers from Houston Methodist Research Institute, Houston Methodist Hospital, institutions in Finland and Iceland, and the U.S. National Institute of Allergy and Infectious Diseases report their discoveries and implications for future studies of epidemic diseases in an upcoming Journal of Clinical Investigation (early online).

According to James M. Musser, M.D., Ph.D., principal investigator of the study and chair of the Department of Pathology and Genomic Medicine at the Houston Methodist Research Institute , the collaborative research showed, at the precise nucleotide level, genetic changes that contributed to large epidemics of group A streptococcus (GAS).

"These findings now give us the opportunity to begin to develop new translational medicine tools and strategies," said Musser. "We can use this information to develop novel therapeutics, advanced diagnostic techniques and new ways to prevent, or dampen, epidemics."

According to the World Health Organization, GAS causes more than 600 million cases of human disease every year. The majority of cases are group A streptococcus pharyngitis, more commonly known as strep throat. But group A strep is also the major cause of preventable childhood heart disease caused by rheumatic fever and . On the far end of the infection severity spectrum, group A streptococcus also causes necrotizing fasciitis ("flesh-eating" disease), an infection with a high mortality rate.

The collaborating team of international scientists found that group A streptococcus was an excellent model organism to study the molecular basis of epidemic bacterial infections. Researchers have known for more than a century that this pathogenic bacterium can cause epidemics, but no one has been able to fully address the cause. Now with next generation sequencing, scientists are able to sequence the entire genome of the bacteria, just as is done in humans. Group A streptococcus was selected as the model organism for study due to the availability of comprehensive strain samples collected over decades, and its relatively small genome, which allows the genome of thousands of strains to be completely sequenced relatively rapidly.

The researchers' original hypothesis, which turned out to be correct, was that changes in the genetic make-up of the GAS pathogen had underpinned new epidemics. To address this hypothesis, the collaborating international team sequenced the genome of thousands of disease-causing strains, precisely defining every base pair mutation in the strains.

"The surprise was that the changes involved alterations in the genes encoding two potent toxins that contribute to human infections," said Musser, who is director for the Center for Molecular and Translational Human Infectious Disease Research at Houston Methodist.

The researchers found that in the epidemic form of group A streptococcus, which can manifest as necrotizing fasciitis, or "flesh-eating" disease, there were two significant and crucial changes within the regulatory region of the epidemic strains. The regulatory region identified controls how two key toxin-encoding genes are transcribed and the toxic proteins made. These specific genetic changes result in the creation of single nucleotide polymorphisms, or SNPs.

Musser's team found that two of those SNPs result in significantly increased production of two important toxins that harm humans called streptolysin O and NAD-glycohydrolase. The third SNP creates a form of one of those toxins that becomes more active than the original form. All three of these SNPS contributed to building a pathogenic organism that is a more virulent machine capable of causing epidemics.

"Think about the thermostat in your house that controls temperature. If you want to make your house hotter, or if group A streptococcus wants to make itself 'hotter,' that is, more virulent, it turns up the heat by making more of these two toxins that harm human cells," said Musser.

Musser and team are hopeful findings from their model study will allow other infectious disease researchers to use analogous strategies that focus on other pathogens, like Staphylococcus aureus (the leading cause of skin and soft-tissue infections), and antibiotic-resistant bacteria such as Klebsiella pneumonia or Escherichia coli.

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Scientists pinpoint when harmless bacteria became flesh-eating monsters

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Citation: Scientists identify a mechanism of epidemic bacterial disease (2015, August 10) retrieved 18 January 2019 from
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Aug 10, 2015
All three of these SNPS contributed to building a pathogenic organism that is a more virulent machine capable of causing epidemics.

Not without a link from thermodynamic cycles of protein biosynthesis and degradation in the context of nutrient-dependent pheromone-controlled RNA-mediated amino acid substitutions in the organized genomes of all genera, they don't.

Did they miss the requirement for the fixation of the amino acid substitutions, or is it mentioned in their publication?

Aug 10, 2015
By the time non-subscribers to this journal see the latest report, my comments to MedicalXpress will be forgotten.

Meanwhile, see: http://www.jci.or...ew/38095

"...recent work has shown that transcript levels of genes encoding proteins involved in carbohydrate catabolism and genes encoding virulence factors change in concert in response to environmental stimuli (74, 75)"

My comment: Given that fact, if they have not yet linked the nutrient-dependent pheromone-controlled physiology of reproduction to organism-level thermoregulation in these organisms, they have probably not noticed that RNA-mediated amino acid substitutions stabilize the organized genomes in all genera.

Aug 10, 2015
"Researchers from Houston Methodist Research Institute, Houston Methodist Hospital, institutions in Finland and Iceland, and the U.S. National Institute of Allergy and Infectious Diseases report their discoveries and implications for future studies of epidemic diseases in an upcoming Journal of Clinical Investigation (early online)."


Retired lab tech
Promoter of young earth creationism
Seller of pseudoscience "perfume"
Master of deflection when challenged
Pathological misinterpreter of the research of real scientists
Has a messiah complex


The authors of the study

Aug 10, 2015
This isn't a game. People are dying of infections and some researchers don't understand the basics of biophysically constrained nutrient-dependent protein folding chemistry during thermodynamic cycles of protein biosynthesis and degradation.

Introduction: The epigenetic effects of nutrients on intracellular signaling and stochastic gene expression appear to enable adaptive evolution of tightly controlled organism-level thermoregulation in mammals. Nutrient-dependent single amino acid substitutions and de novo protein biosynthesis exemplify the involvement of the seemingly futile thermodynamic control of intracellular and intermolecular interactions in microbes that result in stochastic gene expression.

Thermodynamically "futile" cycles of RNA transcription and degradation...

5.5 minute video:

Aug 10, 2015
See also: Bacterial self-organization: co-enhancement of complexification and adaptability in a dynamic environment http://rsta.royal...abstract

Excerpt: "The notion of informative communication corresponds to my view of bacteria as `adaptable generators', that is, they alter themselves according to information received from the environment and send signals to bring about (generate) changes in other bacteria."

They must adapt to virus-perturbed protein folding via nutrient-dependent RNA-mediated DNA repair, which is perturbed by nutrient stress or social stress in species from microbes to man because the molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA are the same.

For example: http://www.ncbi.n...24693353 "The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance..."

Aug 10, 2015
See also: http://www.pnas.o...abstract
"The provisioning of insulators by MIRs across the human genome suggests a specific mechanism by which TE sequences can be used to modulate gene regulatory networks."

Vietvet is Steven Taylor, who has already verified the facts about viruses and cell type differentiation in Greg Bear's science fiction novels included links to my works on human pheromones.

See: http://www.gregbe...?id=8064

The facts support the views expressed by creationists who have followed the scientific progress that has been made by researchers who have linked microRNAs to messenger RNAs and ecological variation to ecological adaptation via the model we published in 1996.

See our section on molecular epigenetics and ask why the moderators at MedicalXpress do not eliminate biologically uninformed antagonists. http://www.hawaii...ion.html

Aug 10, 2015
Pathological misinterpreter of the research of real scientists

Excerpt from our 1996 review: "Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes."

It now appears that the MIRs /pre-mRNAs are linked from virus-driven entropic elasticity to genomic entropy when nutrient-dependent pre-mRNAs do not link their anti-entropic nutrient energy from RNA-mediated events to cell type differentiation in all cell types of all living genera.

Aug 10, 2015
Steven Taylor is a pathological influence on discussion here and may be contributing to forthcoming terrorist threats that could be prevented or effectively contained by what is currently known to serious scientists about viruses and RNA-mediated cell type differentiation.

Greg Bear joked about the threats on the Jon Stewart show several years ago, but the joking did not make the threats less real. People should ask what makes biologically uninformed science idiots like Steven Taylor into antagonists who contribute nothing to discussion except denigration of my works and the works of other serious scientists. What motivates Steven Taylor. Dissemination of accurate information motivates me.

See http://thedailysh...reg-bear
For comparison: Greg Bear - Doctors on the Front Lines: Adjusting Patient Care in an Age of Changing Paradigms https://www.youtu...0le52U20

Aug 10, 2015

" who has already verified the facts about viruses and cell type differentiation in Greg Bear's science fiction novels "

What a crock.

Aug 10, 2015
"Dissemination of accurate information motivates me."


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