BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: antibiotics

CRISPRi Antibiotics: Will Pathogens Cease to Exist?

Recently, a researcher at the University of Wisconsin-Madison and his collaborators at the University of California, San Francisco have discovered a way to repurpose CRISPR, a gene-editing tool, to develop new antibiotics.

What does this mean?

It is known that many disease-causing pathogens are resistant to current antibiotics. This new technique, Mobile-CRISPRi, is helping to change that. Mobile-CRISPRi allows scientists to “screen for antibiotic function in a wide range of pathogenic bacteria.” Scientists used of bacterial sex to transfer Mobile-CRISPRi from laboratory strains into any diverse bacteria. This easily transferred technique will now allow scientists to to study any bacteria that cause disease or help one’s health.

To break it down, Mobile-CRISPRi “reduces the production of protein, from targeted genes, allowing researchers to identify how antibiotics inhibit the growth of pathogens.” This will allow researchers to more thoroughly understand different bacterias’ resistance to current antibiotics.

Unlike CRISPR, which can split DNA into two halves, CRISPRi is a defanged form that is unable to cut DNA. Instead, it stays on top of the DNA, blocking other proteins from being able to turn on a specific gene.

Genes (DNA)

Why is this important?

It has been proved that a decrease in the amount of protein targeted by an antibiotic will make bacteria become more sensitive to lower amounts of that same antibiotic. This evidence association between “gene and drug” has allowed scientists to “screen thousands of genes at a time,” as they try to gain more knowledge about the mechanisms of how antibiotics work in organisms to improve those on the market now.

In order to study how antibiotics directly work in pathogens, researchers needed to make this CRISPRi mobile, or easily transferred onto different bacterias. There were two tests done to test CRISPRi’s mobility using conjugation. One involving a transfer of CRISPRi to the pathogens Pseudomonas, Salmonella, Staphylococcus, Listeria, and others, and another involving the bacteria that grows on cheese.

Science Daily describes the “landscapes of microbes cheese creates as it ages.” A bacteria called “Vibrio casei” was found on a French cheese in a lab back in 2010. With bacteria that have been taken out of their environment, it is hard to manipulate and study said pathogen’s genes, like “Vibrio casei.”

However, the mobile-CRISPRi was able to easily transfer onto the strain of  Vibrio casei that was discovered back in 2010. This has given scientists a new way of understanding how bacteria colonizes and ages cheese.

Peters, the head researcher of mobile-CRISPRi is generous enough to offer this system to other scientists who would like to study other germs. With this technology being available to others, scientists could potentially see first-hand how antibiotics work in pathogens, and use that information to improve those that currently exist, hopefully getting rid of these bacterias like pseudomonas, or listeria before they kill the human they are inside of.

How Non-Antibiotic Drugs May Affect the Human Microbiome

Scientists at the European Molecular Biology Laboratory (EMBL) in Germany tested 1200 medications on 38 types of gut bacteria to see if some non-antibiotic medications still affect bacteria. 835 of these medications were human-cell-targeting, such as anti-inflammatory drugs and antipsychotic compounds. Testing showed that around one-quarter of the drugs tested affected the growth of gut bacteria. The scientists are still unsure if this means that the drugs are harmful. The inhibition of bacterial growth could contribute to the drugs’ side effects, or even be “part of the drugs’ beneficial action.”

The scientists also found a connection between bacteria that weren’t affected by the medications and antibiotic-resistant bacteria, possibly showing a connection between the use of non-antibiotic drugs and the increase in antibiotic resistance, which is a major issue.

Nevertheless, this study advances how we think about medications and their effects on our microbiome, and helps us to understand our own bodies better.

Image result for antibiotics

Antibiotics

Killer Cells Caught Red-Handed!

Antibiotics are most commonly used to treat bacterial infections, but bacteria are rapidly able to evolve and resist these drugs, contributing to superbugs. Immune killer cells or white blood cells, however, are seemingly more effective at destroying bacteria cells. How do our immune cells fight bacteria so efficiently? What exact mechanisms do killer cells use to track and destroy bacteria and can we replicate those mechanisms with drugs?

Image result for white blood cells

White Blood Cell (farthest to right)

A common way immune cells can the trigger death of bacteria is by oxidizing the bacterial cells. However, immune cells are still able to destroy bacteria in environments without oxygen leading scientists to believe other methods are also used in attacking bacteria.

Scientists have recently discovered that immune cells methodically kill cells without the use of oxygen. The immune cells do this by shooting enzymes into bacteria to program the bacteria to self-destruct. Scientists have discovered this by observing immune killer cells as they destroy E. coli and the bacteria responsible for Listeria and tuberculosis. They measured the protein levels of each different bacteria before, during, and after the immune cells killed the bacteria. Each bacterial strain started with about 3000 proteins and ended up losing around 10% of their proteins due to the immune cells injected enzyme called granzyme B. Those 10% of proteins destroyed, however, were necessary to the survival of each bacteria. Granzyme B also shuts down ribosomes preventing the bacteria from making new proteins.

This discovery is significant at a time where antibiotics are becoming less efficient and superbugs are becoming prevalent.  Scientists hope to design a new drug that will treat bacterial infections in a similar way to our own immune killer cells.

The 450 Million Year Old Superbug

The first superbug may have occurred 450 million years ago when animals decided to leave the water and begin to live on land.  The scientists at the Broad Institute found evidence displaying a group of antibiotic-resistant bacteria which are as old as the first land animals. Like us humans, the animals possessed these superbugs in their guts. Since the bacteria has been around for so long it has given it time to adapt and develop necessary traits to make it resistant to antibiotics like penicillin. The specific superbug which has lasted since the first land animal is Enterococci.

Photo by Eric Erbe

They can be considered the “godfather” of superbugs. Enterococci were found during the 80’s and were one of the first pathogens to be known to resist antibiotics. Enterococci bacteria today is a major cause of hospital infections in the United States and infects up to 70,000 Americans and kills up to 1,000 each year. Enterococci is so special because it possesses a number of genes which are focused on “hardening and fortifying” the cell wall. The reinforced cell wall allows for the bacteria to fight off disinfectants and not dry out. Research also shows that the fortification was added around the same time that animals began to come ashore. Since the two events happened around the same time it is assumed that the new fortification was to assist the survival of the bacteria in the new environment.

Enterococci had to create new fortification against new elements on land which was not present in the water. Since Enterococci is located in the gut some are excreted through feces. In water, the excreted Enterococci would end up at the bottom of the ocean floor which was moist and filled with nutrients, similar to the guts of a marine animal. When the Enterococci was released on land it would meet a harsher environment where they were exposed to Ultra-violent light from the sun. This caused the bacteria to dry up and die. Eventually, the bacteria developed and picked up the fortification needed which now helps them to thrive in hospitals. Their shell from 450 million years ago allows them to be resistant to the typical effects of cleaning measures in hospitals. The protection the bacteria has is what causes it to be considered a superbug. Even though superbugs are becoming more prominent the understanding of the so-called “godfather” of superbugs may help us to find ways to defeat Enterococci and hopefully other superbugs.

Could a new bacterial test reduce the chances of new superbugs emerging?

We’ve all suffered from a nasty bacterial infection of some sort, like strep or a sinus infection. Usually, we go to the doctor and are prescribed antibiotics, and are cured in a few days. The problem with this is that bacteria are becoming multi-drug resistant and skipping over weaker antibiotics and immediately using stronger ones to increase the effectiveness. This is because to test out if an infection is resistant to antibiotics, a doctor would have to send a sample to a lab and wait 2-3 days for the results (Fore more information on standard bacterial lab tests, click here). The more antibiotics that are overused and misused, the more super-bugs (multi-drug resistant bacteria) will emerge.

Luckily, there is a new advancement in testing bacterias resistance to antibiotics. A new test has been developed at Caltech that can identify antibiotics resistant bacteria in as little as thirty minutes. The test was focused on UTI’s; they took a sample of infected urine and divided into two groups. One group was incubated, and the other was exposed to antibiotics for fifteen minutes. The bacteria were then lysed, or broken down, to release their cellular contents. The contents are then run through a process combining d-LAMP and Slip chips. This process replicates specific DNA markers which are imaged and counted as fluorescent spots on the chip.

This Photo is credited to Wikipedia

The logic behind this test is that antibiotics affects the DNA replication of bacteria, so there will be less fluorescent spots on the chip for bacteria that is not resistant to bacteria. If the DNA are resistant to bacteria, the DNA replication, fluorescent spots, will be the same in both groups. The tests had a 95% match with the standard two day test, (hyperlink info about standard test) and was tested on 54 subjects with UTI’s caused by the same bacteria, Escherischia Coli.

The creators of this test, Ismagilov, Schoepp, and Travis Schlappi, are continuing to test other bacterial infections, and hope to modify the test to be able to test blood infections. Blood infections are more difficult to test because the presence of bacteria in blood is significantly less than in urine. Having a test like this, for many types of different bacteria, which could be performed in one doctors visit would help reduce the overuse and misuse of bacteria, thus decreasing the chance of new superbugs emerging.

For more information and visuals click here.

 

Parents Take Warning: Antibiotics Can Be Harmful to Infants

Antibiotics are the marvel of modern medicine. They have brought about incredible medical advances, treating bacterial diseases and helping to prolong lifespans in modern times. But a new study conducted by researchers at the Massachusetts General Hospital and the Broad Institute has shined a light on the potential negative effects antibiotics can have on an infant’s health.

https://www.flickr.com/photos/herebedragons/2573487530

The study, conducted in partnership with a team of Finnish researchers, took monthly fecal samples from 39 children from birth until they were 36 months old and analyzed the sample using standard, RNA sequencing procedure to identify different microbes. During the study, 20 of the children had taken antibiotics for respiratory or ear infections ranging from 9 to 15 treatments over the course of the study. From this data, the researchers could analyze the diversity of the gut microbiome of these participants with respect to their antibiotic usage.

The researchers had chosen to analyze the effect antibiotics have on the gut microbiome in young children because of the pivotal role antibiotics appear to play in human health during early development. Low diversity in the early years of life of this collection of bacteria residing in the intestines has been linked to allergies and autoimmune diseases.

The results of this study show a decrease in the diversity of the microbial gut populations in infants who took antibiotics. This was even more pronounced when the infants were marked with a specific signature low in a bacteria known as Bacteriodes (this decrease in Bacteriodes has been speculated to be linked to Caesarean section births in the past but the researchers found this rationale to be inconclusive as well as another rationale that prolonged breastfeeding led to a stronger gut microbiome with higher levels of Bifidobacteria).

When the infants had taken antibiotics, a single strain of bacteria tended to rule their gut with only a few species surviving. On the whole, the gut microbiomes of these participants were less stable and had higher levels of antibiotic resistant genes.

Don’t get me wrong: antibiotics are an incredible innovation that has saved millions of lives. But, be careful in thinking they are a cure all. They’re side-effects might be more harmful than you think, especially in children.

How does this research change your perception of antibiotics?

 

Infants’ Feces Says a Lot about the Gut Microbiome

Who knew studying babies’ poop can actually lead to amazing discoveries about childbirth, breastfeeding, antibiotics, allergies, and asthma?

That’s exactly what scientists Fredrik Bäckhed and Jovanna Dahlgren at the University of Gothenburg, Sweden, and Wang Jun at the Beijing Genomics Institute-Shenzhen, China recently learned when they conducted a study analyzing feces from 98 Swedish infants.

But before we get into the details of the study, let’s get down the basics first. What exactly is the gut microbiome?

Gut microbiome is the name given to the population of microbiota organisms that live in the human intestine. These microorganisms are unique, not only because there are trillions of them but also because they have milliions of genes, and can function as a person’s identity card (much like a fingerprint or a strand of hair).

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(Source: https://en.wikipedia.org/wiki/Fecal_bacteriotherapy#/media/File:E_coli_at_10000x,_original.jpg)

Recently there’s been a lot of buzz in the science world about the gut microbiome because it seems as though it plays various crucial functions, and this study is just one of many. The Swedish and Chinese scientists discovered a few ways in how the gut microbiome affects childbirth, breastfeeding, and development.

There are two ways to give birth: vaginally or via a cesarean section, or C-section. Comparing the feces collected from babies born vaginally and from babies born via C-section, scientists discovered that the feces from the latter contains a significantly less similar microbiome to the microbiome of their mothers.

They also determined that nutrition during the early stages of an infant’s life is a core factor in the development of the gut microbiome.

Our findings surprisingly demonstrated that cessation of breastfeeding, rather than introduction of solid foods, is the major driver in the development of an adult-like microbiota

-Fredrik Bäckhed, lead study author

Bacteria rely on the mother’s milk to grow. Once the bacteria’s access to that milk stops, the bacteria stops growing. In its place, adult-like microorganisms emerge.

In addition, the gut microbiome acts as nutrients and vitamins to the infant’s growth and development, and gives aid to important processes such as making amino acids.

The study also critiques the amount of antibiotics given to babies when they’re born. There’s speculation that the baby’s gut microbiome is negatively impacted by the overabundance and overexposure of antibiotics. Besides the obvious risk of antibiotic resistance, one hypothesis is that when exposed to antibiotics early on, the gut microbiome loses important bacteria that helps immune cells mature. This is believed to be the reason why allergies and asthma are now widely prevalent.

Though this study is just a preliminary, it’s amazing just how big of an effect the gut microbiome has on us, and how much new research is coming out.

Want to learn more about the gut microbiome? Check out other sources about the microbiome, such as it’s relationship on the brain, and how it can change the brain’s function, how it can help reduce weight, and junk food’s negative impact on it, and make sure to comment below!

 

 

Original Article

Attention all penicillin-allergy victims, you might not actually be penicillin-allergic!

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Photo of antibiotics (licensing information here)

I am someone who is allergic to penicillin, amoxicillin, and a bunch of other “cillins”. So, when being prescribed with antibiotics, penicillin is always ruled out as an option for treatment. However, new findings at the American College of Allergy, Asthma, and Immunology (ACAAI) show that people, like me, who were told after a single allergic reaction to penicillin that they were penicillin-allergic, may not be penicillin-allergic after all!

At the Annual Scientific Meeting at the ACAAI, a study was presented where 15 students who were supposedly penicillin-allergic tested negative for a penicillin allergy and were in fact treated with intravenous penicillin medication multiple times. Dr. David Khan and Dr. Roland Solensky, both allergists, are both majorly involved in this research. They each stated that people who are found allergic to a medication such as penicillin are then prescribed with more expensive and dangerous medications to take the place of the medication they are allergic to. In fact, almost 10% of Americans are labeled penicillin-allergic and have no choice but to use more complex medications, when they might not even be allergic to a simpler medication, such as penicillin, in the first place!

To attempt to resolve this problem, Dr. Solensky is going to present “Drug allergy: options beyond avoidance” at the next Annual Meeting at the ACAAI. This presentation is designed to discuss different treatment options for patients suffering from allergies to certain medications, as well as patients who were told they are allergic to medications that they are in fact not allergic to. Dr. Khan encourages everyone who is penicillin-allergic to get tested and see if penicillin is a medication they should actually avoid or if the allergic reaction they once had to penicillin was a fluke. This study can help people avoid medications that are overly expensive or that can be dangerous, and just in general help people find more appropriate medications. I sure know that I’m interested to see if I’m actually penicillin-allergic, or if that allergic reaction I had in second grade was a one time thing!

Main article:

http://www.biologynews.net/archives/2015/11/05/consider_penicillin_even_if_you_have_had_a_prior_reaction.html

Animal Overdose and Its Effect on Humans

As we all know, antibiotics can be used to cure infections and kill bacteria, but the also often come with the many side effects that the infomercials so quickly warn us of. However, we often overlook aspects of antibiotics and rely on them to heal us in a variety of ways.

This then causes too much reliance on antibiotics, and in fact, humans are becoming immune to these medicines and too much use takes from their ability to have positive results.

This displays the alignment of veal that has been modified and undergone treatment to fight possiblebacteria.

This displays the alignment of veal that has been modified and undergone treatment to fight possible bacteria.

Animals have been receiving harsh treatment and experience weight gain as a result of being given antibiotics for growth promotion in order to sell more meat without disease.  However, animals experience the same resistance over time. The Environmental Working Group is concerned about this, because most of the meat sold in grocery stores is made up of a large amount of antibiotic-resistant bacteria. This, too, can easily be passed on to humans by consumption, as the Food and Drug Administration states.

Due to this resistance to antibiotics and its misuse, many are concerned that the amount of antibiotics served to both humans and animals needs to be lowered, which is much easier said than done. The ultimate goal would be to continue to fight bacteria as opposed to promoting its resistance, as one would assume. However, it is interesting to know how large of an affect antibiotics have on both the human and animal reactions in their bodily systems, and how misuse can alter the bacteria as well as the reason for their need.

Article Link:

http://www.scientificamerican.com/article/what-are-the-consequences-of-antibiotic-overuse/

Additional Links:

http://www.cdc.gov/narms/animals.html

http://www.pbs.org/wgbh/pages/frontline/shows/meat/safe/overview.html

http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm378100.htm

Image Link:

http://en.wikipedia.org/wiki/Veal#mediaviewer/File:MIN_Rungis_viandes_de_boucherie_veau.jpg

 

Are Antibiotics Killing More Than Just Infections?

What are in your antibiotics?

We all take antibiotics. Staph infections, Strep throat, etc. and they get the job done. Within two or three days, sometimes a week, you’re cured and infection-free. But is that really best for us?

Microbiomes are what make us so unique and individual. In fact, we have more bacteria cells that human cells in a 10 to 1 ratio. We have different microbiomes for different parts of the body; our mouth has a different microbiome than our skin microbiome which has a different microbiome than our gut microbiome. We can influence our microbiomes by what we eat, or rather they influence us based on what we eat. As part of an evolutionary benefit, our microbiomes adapt to newly introduced food within days, which we previously thought took years to change. In other words, if you didn’t eat carrots for three years and sporadically ate carrots one day, your microbiome would activate bacteria that was previously dormant to digest the carrots within days. Think for a moment: a bacteria your body hadn’t made in three years is suddenly recolonized and active in helping you digest within a few days. It’s truly amazing! However, the rest depends on how you were born.

If you were vaginally born, your first encounter with bacteria (bacteria from the placenta is still controversial as to whether babies acquire some of their intestinal bacteria before birth) was in the birth canal, which is exactly where you get your microbiota colonies from. If you were Cesarean born, you might find that you have a higher chance of chronic conditions like asthma or Celiac’s disease simply because you received your mother’s skin microbiome instead of her vaginal microbiome. If you were not breast fed, you are more likely to contract similar conditions because breast milk contains nutrients that cannot be broken down by your digestive track. Rather, they surpass your digestive track and nourish microbiota. Formulas were unaware of this and therefore did not contain everything necessary for your microbiota health, but formulas have been making adaptions to fully mimic these qualities of breast milk.

Say you did all of the right things: you eat whole, unprocessed foods that can nourish your microbiome, you were vaginally born and you were breastfed. It’s completely possible that you have a wonderful, flourishing microbiome. However, you likely do not.  Processed foods do not contain enough prebiotic nutrients (food for microbes). Although one associates Western civilization with nutrition and health, we are actually considered “impoverished” in the world of microbiomes.

The big problem with the Western diet is that it doesn’t feed the gut, only the upper G I. All the food has been processed to be readily absorbed, leaving nothing for the lower G I. But it turns out that one of the keys to health is fermentation in the large intestine. Stephen O’Keefe

Those with no contact to the Western world and its medicine, pesticides, sterility and processed foods have a rich and diverse microbiome. Not to mention the growth hormone in cows, which changes the microbiota for a hastened growth as well as the metabolism of the liver. They even stimulate an increase in body fat. Western medicine, however, affects us in less visible manner. Our antibiotics are too strong for our own good; they destroy the pathogenic bacteria, yes, but they also destroy the health-promoting ones. Therefore, some argue that we should improve our diagnostics to prescribe fewer and narrow-spectrum antibiotics to kill the harmful bacteria while reducing the collateral damage. (Dr. Blaser) These heavy duty antibiotics not only destroy the healthy, diverse microbiota, but have a permanent effect if used for a second course; the microbiome will bounce back but it will not be able to return to its original state. In addition to this, antibiotics have been trying to eliminate H. pylori since 1983 when they found it could lead to stomach cancer or peptic ulcers, when in fact its disappearance could be contributing to acid reflux and obesity. Due to our continual efforts to eliminate H. pylori from the microbiome, it is unlikely that we will see it in upcoming microbiomes due to antibiotics, and “each generation is [already] passing on fewer of this microbes.” Prevotella, for example, is a gut bacteria extremely difficult to find in Western society but relatively common in underdeveloped countries. One woman had unusually high levels of this bacteria in her microbiome, but after one course of antibiotics for oral surgery, her wonderful microbiome was reduced to the average American bacterial standards. 

One of the more striking results from the sequencing of my microbiome was the impact of a single course of antibiotics on my gut community. My dentist had put me on a course of Amoxicillin as a precaution before oral surgery. (Without prophylactic antibiotics, of course, surgery would be considerably more dangerous.) Within a week, my impressively non-Western “alpha diversity” — a measure of the microbial diversity in my gut — had plummeted and come to look very much like the American average. My (possibly) healthy levels of prevotella had also disappeared, to be replaced by a spike in bacteroides (much more common in the West) and an alarming bloom of proteobacteria, a phylum that includes a great many weedy and pathogenic characters, including E. coli and salmonella. What had appeared to be a pretty healthy, diversified gut was now raising expressions of concern among the microbiologists who looked at my data.

Her bacterial composition will return to something that somewhat resembles her original microbiome, but every course after that will decrease potential microbial recovery and also decrease invasion resistance (keeps pathogens from gaining a toehold by occupying potential niches or otherwise rendering the environment inhospitable to foreigners e.g. H. pylori regulates stomach acid to make the environment unfavorable to other bacteria that wants to colonize; vaginal pH is kept low so the environment is too acidic for foreign bacteria to colonize, etc.) So the next time you take an antibiotic, ask yourself: what am I doing to my microbiome?

The “Social” Bacteria

800px-M._xanthus_development        The Myxococcus xanthus is a bacterium found in soil that scientist identify as a “social” bacteria. Organized into multi-cellular and three-dimensional structures made of thousands of cells, the bacterium works together by hunting for food and surviving under difficult conditions. They form interesting structures and help each other survive, which are fascinating points of study for scientists who have been researching E. Coli (which has medical significance and influence) in test tubes. However scientists believe that this behavior in test tubes is obviously not as revealing as bacteria behavior in a social or spacial structure that they find in Myxococcus xanthus.

       Myxococcus xanthus eats other microbes and is therefore classified as “predatory”. The structural complex that the thousands of cells form interests scientists, because it is self-made and because it can hunt, kill, and digest various different microbes. By identifying the mechanisms that help the bacteria achieve their multi-cellular behaviors, scientists believe that this will answer questions about how individual cells break their symmetry to organize into these complicated many-celled compositions, teaching scientists about the evolution of multi-cellularity. “The most primitive form of life is single-cell life,” Igoshin, a scientific investigator, says. “The next step up would be going from single cells to multicellular organisms. These bacteria are somewhat in the middle.”

      The bacterium is capable of adopting various forms (ripples, segments, fruiting bodies) in order to hunt for food successfully as a unit and live for a long time together. These capabilities give researchers insight into designing future antibiotics by understanding its functions and methods, especially in embryonic development and other manifestations of this kind. 

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