Abstracts from the International Science Symposium on HIV and Infectious Diseases (ISSHID 2019): Infectious diseases
New Compound Found To Be Effective Against 'flesh-eating' Bacteria
Researchers at Washington University School of Medicine in St. Louis have developed a novel compound that effectively clears bacterial infections in mice, including those that can result in rare but potentially fatal "flesh-eating" illnesses. The compound could be the first of an entirely new class of antibiotics, and a gift to clinicians seeking more effective treatments against bacteria that can't be tamed easily with current antibiotics.
The research is published Aug. 2 in Science Advances.
The compound targets gram-positive bacteria, which can cause drug-resistant staph infections, toxic shock syndrome and other illnesses that can turn deadly. It was developed through a collaboration between the labs of Scott Hultgren, Ph.D., the Helen L. Stoever Professor of Molecular Microbiology, and Michael Caparon, Ph.D., a professor of molecular microbiology, and Fredrik Almqvist, a professor of chemistry at the University of Umeå in Sweden.
A new type of antimicrobial would be good news for clinicians seeking effective treatments against pathogens that are becoming more resistant to currently available drugs, and thus much more dangerous.
"All of the gram-positive bacteria that we've tested have been susceptible to that compound. That includes enterococci, staphylococci, streptococci, C. Difficile, which are the major pathogenic bacteria types," said Caparon, the co-senior author. "The compounds have broad-spectrum activity against numerous bacteria."
It's based on a type of molecule called ring-fused 2-pyridone. Initially, Caparon and Hultgren had asked Almqvist to develop a compound that might prevent bacterial films from attaching to the surface of urethral catheters, a common cause of hospital-associated urinary tract infections. Discovering that the resulting compound had infection-fighting properties against multiple types of bacteria was a happy accident.
The team named their new family of compounds GmPcides (for gram-positive-icide). In past work, the authors showed that GmPcides can wipe out bacteria strains in petri dish experiments. In this latest study, they decided to test it on necrotizing soft-tissue infections, which are fast-spreading infections usually involving multiple types of gram-positive bacteria, for which Caparon already had a working mouse model.
The best known of these, necrotizing fasciitis or "flesh-eating disease," can quickly damage tissue severely enough to require limb amputation to control its spread. About 20% of patients with flesh-eating disease die.
This study focused on one pathogen, Streptococcus pyogenes, which is responsible for 500,000 deaths every year globally, including flesh-eating disease. Mice infected with S. Pyogenes and treated with a GmPcide fared better than did untreated animals in almost every metric. They had less weight loss, the ulcers characteristic of the infection were smaller, and they fought off the infection faster.
The compound appeared to reduce the virulence of the bacteria and, remarkably, speed up post-infection healing of the damaged areas of the skin.
It is not clear how GmPcides accomplish all of this, but microscopic examination revealed that the treatment appears to have a significant effect on bacterial cell membranes, which are the outer wrapping of the microbes.
"One of the jobs of a membrane is to exclude material from the outside," Caparon said. "We know that within five to ten minutes of treatment with GmPcide, the membranes start to become permeable and allow things that normally should be excluded to enter into the bacteria, which suggests that those membranes have been damaged."
This can disrupt the bacteria's own functions, including those that cause damage to their host, and make the bacteria less effective at combating the host's immune response to infections.
In addition to their antibacterial effectiveness, GmPcides appear to be less likely to lead to drug-resistant strains. Experiments designed to create resistant bacteria found very few cells able to withstand treatment and thus pass on their advantages to the next generation of bacteria.
Caparon explained that there is a long way to go before GmPcides are likely to find their way into local pharmacies.
Caparon, Hultgren and Almqvist have patented the compound used in the study and licensed it to a company, QureTech Bio, in which they have an ownership stake, with the expectation that they will be able to collaborate with a company that has the capacity to manage the pharmaceutical development and clinical trials to potentially bring GmPcides to market.
Hultgren said that the kind of collaborative science that created GmPcides is what is needed to treat intractable problems like antimicrobial resistance.
"Bacterial infections of every type are an important health problem, and they are increasingly becoming multi-drug resistant and thus harder to treat," he said.
"Interdisciplinary science facilitates the integration of different fields of study that can lead to synergistic new ideas that have the potential to help patients."
More information: Zongsen Zou et al, Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds treat Streptococcus pyogenes skin and soft tissue infection, Science Advances (2024). DOI: 10.1126/sciadv.Adn7979. Www.Science.Org/doi/10.1126/sciadv.Adn7979 .
On BioRxiv: DOI: 10.1101/2024.01.02.573960
Citation: New compound found to be effective against 'flesh-eating' bacteria (2024, August 2) retrieved 29 August 2024 from https://phys.Org/news/2024-08-compound-effective-flesh-bacteria.Html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
A Breakthrough In Fighting Bacteria That Causes 'flesh-eating' Illness
An international team of scientists has developed a new family of compounds that can clear bacterial infections in mice. Some of these infections can result in serious "flesh-eating" illnesses. There are about 700 to 1,100 cases of flesh-eating illnesses every year in the United States. The new family of compounds could also represent the beginning of a new class of antibiotics and are described in a study published August 2 in the journal Science Advances.
Growing resistanceFor decades, clinicians have been sounding the alarm about pathogens that are increasingly becoming more resistant to drugs currently available. This makes them more dangerous and according to the Centers for Disease Control and Prevention (CDC), over 2.8 million antimicrobial-resistant infections occur in the US every year. More than 35,000 people die from these infections. To combat this, newer antimicrobial compounds will be needed to replace the ones that bacteria have become resistant to.
Molecular microbiologists Scott Hultgren and Michael Caparon from Washington University School of Medicine in St. Louis and chemist Fredrik Almqvist from the University of Umeå in Sweden collaborated on this new family of compounds called GmPcides.
[Related: These flesh-eating bacteria are finding new beaches to call home.]
GmPcides work by targeting gram-positive bacteria. These types of bacteria can cause various drug-resistant staph infections, toxic shock syndrome, and other bacterial illnesses that can turn deadly.
"All of the gram-positive bacteria that we've tested have been susceptible to that compound. That includes enterococci, staphylococci, streptococci, C. Difficile, which are the major pathogenic bacteria types," Caparon said in a statement. "The compounds have broad-spectrum activity against numerous bacteria."
A 'happy accident'The new GmPcide compounds are based on a type of molecule called ring-fused 2-pyridone that was developed by what the team calls a happy accident. Caparon and Hultgren had asked Almqvist to develop a chemical compound that can prevent bacterial films from latching onto the surface of urethral catheters. These are a common cause of urinary tract infections in hospital settings.
The resulting compound also had infection-fighting properties against multiple types of bacteria. Some of their earlier research showed that GmPcides can kill bacteria strains in petri dish experiments.
In this new study, they took those petri dish experiments one step further by testing how compounds work on necrotizing soft-tissue infections. These fast-spreading infections usually involve multiple types of gram-positive bacteria. Necrotizing fasciitis–or flesh-eating disease–is the best known of these infections. It can rapidly damage tissue so severely that limb amputation is often necessary to control its spread. Roughly 20 percent of patients with flesh-eating disease die.
The team focused on one pathogen that is responsible for about 500,000 deaths every year–Streptococcus pyogenes. A group of mice was infected with S. Pyogenes. One group was treated with GmPcide, while the other wasn't. Those that received the GmPcide treatment fared better than the untreated mice in almost every metric. They lost less weight, had smaller ulcers, and fought off the infection faster. Damaged areas of skin also appeared to heal quicker post-infection.
While it is still not fully clear how GmPcides did all of this, a microscopic examination showed that the treatment has a significant effect on bacterial cell membranes. These are the outer wrapping of the microbes.
[Related: 'Bacterial glitter' shimmers without pigments.]
"One of the jobs of a membrane is to exclude material from the outside," Caparon said. "We know that within five to ten minutes of treatment with GmPcide, the membranes start to become permeable and allow things that normally should be excluded to enter into the bacteria, which suggests that those membranes have been damaged."
This can alter the bacteria's own functions, including actions that damage the host and make the bacteria less effective at taking down the host's immune response to infections.
GmPcides also may be less likely to lead to drug-resistant strains. The experiments designed to create resistant bacteria found that very few cells can withstand treatment. This means they are less likely to pass on their advantages to the next generation of bacteria.
The road aheadAccording to Caparon, there are still numerous steps before GmPcides will be available at your local pharmacy. The team has patented the compound used and licensed it to QureTech Bio, a company that Caparon, Hultgren and Almqvist have an ownership stake in. The license was contingent on the expectation that they will collaborate with a separate company that can manage the pharmaceutical development and clinical trials to bring it to market.
According to the team, the kind of collaborative science that created GmPcides will be needed to treat the problems like antimicrobial resistance."Bacterial infections of every type are an important health problem, and they are increasingly becoming multi-drug resistant and thus harder to treat," Hultgren said in a statement. "Interdisciplinary science facilitates the integration of different fields of study that can lead to synergistic new ideas that have the potential to help patients."
8 Surprising Things That Harm Your Gut Bacteria
Having a healthy gut flora is incredibly important for your overall health. Many diet, lifestyle and other environmental factors can negatively affect your gut bacteria.
Hundreds of species of bacteria reside in your gut. Some of them are friendly, while others are not.
Most bacteria in the gut belong to one of four groups: Firmicutes, Bacteroidetes, Actinobacteria or Proteobacteria (1, 2).
Each group plays a role in your health and requires different nutrients for growth (3).
The friendly gut bacteria are important for digestion. They destroy harmful bacteria and other microorganisms and produce vitamin K, folate and short-chain fatty acids (4, 5).
When the gut flora contains too many harmful bacteria and not enough friendly bacteria, an imbalance can occur. This is known as dysbiosis (6, 7).
Both dysbiosis and a reduction in gut flora diversity have been linked to insulin resistance, weight gain, inflammation, obesity, inflammatory bowel disease and colorectal cancer (8, 9, 10, 11).
Therefore, it's important to keep your gut bacteria as friendly and abundant as possible.
Without further ado, here are 8 surprising things that can cause harm to your gut bacteria.
1. Not eating a diverse range of foodsGenerally, a rich and diverse gut flora is considered to be a healthy one (12).
A lack of diversity within the gut bacteria limits recovery from harmful influences, such as infection or antibiotics (13, 14).
A diet consisting of a wide variety of whole foods, such as fruits, vegetables and whole grains, can lead to a more diverse gut flora. In fact, changing up your diet can alter your gut flora profile after only a few days (12, 15, 16).
This is because the food you eat provides nutrients that help bacteria grow. A diet rich in whole foods provides your gut with a variety of nutrients that help promote the growth of different types of bacteria, resulting in a more diverse gut flora.
Unfortunately, over the past 50 years, much of the diversity in the Western diet has been lost. Today, 75% of the world's food supply comes from only 12 plants and five animal species (12).
Interestingly, studies show that those living in rural regions of Africa and South America have a more diverse gut flora than those living in the US and Europe (17, 18).
Their diets are generally unaffected by the Western world and are rich in fiber and a variety of plant protein sources.
2. Lack of prebiotics in the dietPrebiotics are a type of fiber that passes through the body undigested and promotes the growth and activity of friendly gut bacteria (19).
Many foods, including fruits, vegetables and whole grains, naturally contain prebiotic fiber.
A lack of them in the diet may be harmful to your overall digestive health (20).
Foods high in prebiotics include:
One study in 30 obese women found that taking a daily prebiotic supplement for three months promoted the growth of the healthy bacteria Bifidobacterium and Faecalibacterium (21).
Prebiotic fiber supplements also promote the production of short-chain fatty acids (22).
These fatty acids are the main nutrient source for the cells in your colon. They can be absorbed into your blood, where they promote metabolic and digestive health, reduce inflammation and can reduce the risk of colorectal cancer (23, 24).
Moreover, foods rich in prebiotic fiber may play a role in reducing insulin and cholesterol levels (25, 26).
3. Drinking too much alcoholAlcohol is addictive, highly toxic and can have harmful physical and mental effects when consumed in large amounts (27, 28).
In terms of gut health, chronic alcohol consumption can cause serious problems, including dysbiosis.
One study examined the gut flora of 41 alcoholics and compared them to 10 healthy individuals who consumed little-to-no alcohol. Dysbiosis was present in 27% of the alcoholic population, but it was not present in any of the healthy individuals (29).
Another study compared the effects of three different types of alcohol on gut health.
For 20 days, each individual consumed 9.2 ounces (272 ml) of red wine, the same amount of de-alcoholized red wine or 3.4 ounces (100 ml) of gin each day (30).
Gin decreased the number of beneficial gut bacteria, whereas red wine actually increased the abundance of bacteria known to promote gut health and decreased the number of harmful gut bacteria like Clostridium.
The beneficial effect of moderate red wine consumption on gut bacteria appears to be due to its polyphenol content.
Polyphenols are plant compounds that escape digestion and are broken down by gut bacteria. They may also help reduce blood pressure and improve cholesterol (31, 32).
Antibiotics are important medicines used to treat infections and diseases caused by bacteria, such as urinary tract infections and strep throat. They work by either killing bacteria or preventing them from multiplying and have saved millions of lives over the past 80 years.
However, one of their drawbacks is that they affect both good and bad bacteria. In fact, even a single antibiotic treatment can lead to harmful changes in the composition and diversity of the gut flora (33, 34, 35).
Antibiotics usually cause a short-term decline in beneficial bacteria, such as Bifidobacteria and Lactobacilli, and can temporarily increase harmful bacteria like Clostridium (36).
However, antibiotics can also lead to long-term alterations in the gut flora. After completing a dose of antibiotics, most bacteria return after 1–4 weeks, but their numbers often don't return to previous levels (37, 38, 39).
In fact, one study found that a single dose of antibiotics reduced the diversity of Bacteroides, one of the most dominant bacterial groups, and increased the number of resistant strains. These effects remained for up to two years (40).
5. Lack of regular physical activityPhysical activity is simply defined as any movement of the body that burns energy.
Walking, gardening, swimming and cycling are all examples of physical activity.
Being physically active has a number of health benefits, including weight loss, lower stress levels and a reduced risk of chronic disease (41, 42, 43, 44).
What's more, recent studies suggest that physical activity may also alter the gut bacteria, improving gut health (45, 46, 47).
Higher fitness levels have been associated with a greater abundance of butyrate, a short-chain fatty acid that's important for overall health, and butyrate-producing bacteria (48, 49).
One study found that professional rugby players had a more diverse gut flora and twice the number of bacterial families, compared to the control groups matched for body size, age and gender (50).
Moreover, athletes had higher levels of Akkermansia, a bacteria shown to play an important role in metabolic health and the prevention of obesity (50, 51).
Similar results have been reported in women.
A study compared the gut flora of 19 physically active women to 21 non-active women (52).
Active women had a higher abundance of health-promoting bacteria, including Bifidobacterium and Akkermansia, suggesting that regular physical activity, even at low-to-moderate intensities, can be beneficial.
Tobacco smoke is made up of thousands of chemicals, 70 of which can cause cancer (53).
Smoking causes harm to nearly every organ in the body and raises the risk of heart disease, stroke and lung cancer (54).
Cigarette smoking is also one of the most important environmental risk factors for inflammatory bowel disease, a disease characterized by ongoing inflammation of the digestive tract (55).
Furthermore, smokers are twice as likely to have Crohn's disease, a common type of inflammatory bowel disease, compared to non-smokers (56).
In one study, smoking cessation increased gut flora diversity, which is a marker of a healthy gut (57).
7. Not getting enough sleepGetting good sleep is very important for overall health.
Studies show that sleep deprivation is linked to many diseases, including obesity and heart disease (58, 59, 60).
Sleep is so important that your body has its own time-keeping clock, known as your circadian rhythm (61).
It's a 24-hour internal clock that affects your brain, body and hormones. It can keep you alert and awake, but it can also tell your body when it's time to sleep (62, 63).
It appears that the gut also follows a daily circadian-like rhythm. Disrupting your body clock through a lack of sleep, shift work and eating late at night may have harmful effects on your gut bacteria (64, 65, 66).
A 2016 study was the first to explore the effects of short-term sleep deprivation on the composition of gut flora (67).
The study compared the effects of two nights of sleep deprivation (about 4 hours per night) versus two nights of normal sleep duration (8.5 hours) in nine men.
Two days of sleep deprivation caused subtle changes to the gut flora and increased the abundance of bacteria associated with weight gain, obesity, type 2 diabetes and fat metabolism (67, 68).
Nevertheless, sleep deprivation's effects on gut bacteria is a new area of research. Further studies are required to determine the impact of sleep loss and poor sleep quality on gut health.
Being healthy isn't only about diet, physical activity and adequate sleep.
High stress levels can also have harmful effects on the body. In the gut, stress can increase sensitivity, reduce blood flow and alter the gut bacteria (69).
Studies in mice have shown that different types of stress, such as isolation, crowding and heat stress, can reduce gut flora diversity and alter gut profiles (70, 71, 72).
Stress exposure in mice also affects bacterial populations, causing an increase in potentially harmful bacteria like Clostridium and reducing beneficial populations of bacteria like Lactobacillus (73, 74).
One study in humans looked at the effect of stress on the composition of gut bacteria in 23 college students (75).
The composition of gut bacteria was analyzed at the beginning of the semester and at the end of the semester during final examinations.
The high stress associated with final exams caused a reduction in friendly bacteria, including Lactobacilli.
While promising, research on the relationship between stress and gut flora is fairly new, and human studies are currently limited.
How to improve gut healthA healthy gut flora that's high in friendly bacteria is essential for overall health.
Here are some tips on how to improve your gut flora:
Your gut bacteria play an important role in your overall health, and disruption to the gut flora has been linked to a number of health problems.
Diet and lifestyle factors, including poor sleep quality, alcohol consumption and inactivity, can harm your gut bacteria.
Alternatively, living a healthy lifestyle characterized by regular physical activity, low stress and a variety of whole foods is the best way to ensure a healthy gut flora.
In many cases, fermented foods and probiotic supplements may help as well.
Comments
Post a Comment