Bacterial antibiotic resistance (Introduction)
by David Turell 
, Thursday, September 01, 2011, 17:43 (4613 days ago)
It is at least 30,000 years old. Most of it comes from lateral gene transfer. and this finding is a very logical discovery. After all, most early antibiotics came from natural fungi living side by side with bacteria. It may be that so-called rapid evolution of resistance is simply reaching back to what is already present for use.-http://the-scientist.com/2011/08/31/the-age-old-fight-against-antibiotics/
Bacterial antibiotic resistance: mechanism explained
by David Turell , Saturday, June 17, 2017, 22:32 (2496 days ago) @ David Turell
Bacteria that produce antibiotics carry naturally protective genes:
https://www.sciencedaily.com/releases/2017/06/170616102117.htm
"Now, research conducted at The Novo Nordisk Foundation Center for Biosustainability -- DTU Biosustain -- at Technical University of Denmark for the very first time shows that antibiotic resistance genes originate from the same place as the antibiotic compounds, i.e. from a group of soil bacteria called Actinobacteria.
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"More than three fourths of all current antibiotics used to treat human infections are produced by Actinobacteria, which at the same time carry antibiotic resistance genes.
"In these experiments, the researchers surprisingly found that many resistance genes in disease-causing microbes (gram negative pathogens) were very similar to resistance genes found in Actinobacteria. Especially in one case, the genes were 100% identical.
"It has been suspected that pathogens can obtain resistance genes from Actinobacteria for half a century. So now with the 100 % identical genes we find the smoking gun," says Postdoc Xinglin Jiang from DTU Biosustain.
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"But by investigating the DNA sequence around the resistance genes, the team figured out how the resistance genes transfer occurred through a new mechanism named "carry back," where the pathogen basically has a primitive form of "sex" with the Actinobacterium and takes up its resistance genes after it dies.
"This gene transfer by carry back could in principle happen where pathogens come into contact with Actinobacteria, like in an animal farm or in soil polluted with untreated hospital waste. In this way, the pathogen can become resistant and endanger human lives in the next round of infection.
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"By following the DNA-transfer, scientists for the very first time showed an unknown mechanism called carry back in which pathogens were able to snatch genes from far-related bacteria via the carry back mechanism. Here is how, in short, the carry back process works:
"1. The Gram negative pathogen injects its DNA into the Actinobacteria. Gram negative bacteria naturally have an ability called conjugation by which bacterial cells can inject their own DNA into other bacterial cells. It is called the bacterial equivalent of sex, because it is usually used to exchange gene information between Gram negative bacteria. But sometimes Gram negative bacteria can also use this mechanism to inject DNA into far-related Gram positive bacteria like Actinobacteria.
"2. Inside the Actinobacteria, the injected DNA recombines with the host's DNA containing resistance genes. After the Actinobacterium dies, the recombinant DNA is released into the environment.
"3. Lastly, the injected DNA can act as "gluing DNA" and mediate the uptake of resistance gene back to the pathogens through a phenomenon called natural transformation."
Comment: this is an expected finding. Bacterial wars go on and they carry defense mechanisms which they can use automatically. Survival doesn't take intelligence. Just pick up the protective genes. Bacteria have been around since the start of life 3.8 billion years ago. This is one reason why.
Bacterial antibiotic resistance: mechanism explained
by David Turell , Monday, February 11, 2019, 17:03 (1893 days ago) @ David Turell
Studies have shown that when antibiotics fail, it is due to a one percent resistant strain in the bacteria. I've explained it before, In nature antibiotics are present and part of wars between bacteria and bacteria and bacteria and fungi. We use naturally produced antibiotics so some bacteria are prepared to recognize them and resist:
https://phys.org/news/2019-02-hard-to-detect-antibiotic-resistance-underestimated-clini...
"When a bacterial infection is suspected, samples are taken for analysis to assess whether the bacterium can be treated with (i.e. is susceptible to) antibiotics or not (i.e. is resistant), and what kind of antibiotic works. Heteroresistance means that while the majority of bacteria in the sample are susceptible to antibiotics, there is also a minor (less than 1 percent) antibiotic-resistant subpopulation that can grow despite treatment with antibiotics.
"No research to date has explained the underlying mechanisms of heteroresistance. As previous studies on humans and animals alike have shown, heteroresistance can make antibiotic treatment ineffective because the resistant subpopulation grows instead of being destroyed.
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"They surveyed the scale on which it was present in four bacteria species that cause infections in humans by exposing them to 28 different kinds of antibiotic. Surprisingly, the results showed that more than a quarter of the combinations of bacteria and antibiotics exhibited heteroresistance.
"This indicates that the frequency of heteroresistance in clinically important bacteria has been greatly underestimated before," says Dr. Hervé Nicoloff, researcher at the Department of Medical Biochemistry and Microbiology, Uppsala University and lead author of the study.
"A range of genetic investigations also enabled the researchers to show that the underlying mechanism of heteroresistance was often spontaneous occurrence of gene amplifications of various antibiotic resistance genes. The bacteria cells containing only one copy of these genes were susceptible to antibiotics, while the cells containing multiple gene copies were resistant.
"These gene amplifications are unstable, and as a result, antibiotic-resistant bacteria can rapidly revert to susceptibility again. This instability makes heteroresistance difficult to detect and study, which is a problem for hospital laboratories that need to determine whether a bacterium is susceptible or resistant to a particular antibiotic. Accordingly, bacteria can be classified as susceptible although they are actually resistant, and this may lead to use of the wrong antibiotic and failure of the treatment."
Comment: As I've previously noted, many bacterial populations have a variety of resistant and non-resistant individuals, so that group will survive on their own without gene transfer, which is another mechanism.
Bacterial antibiotic new resistance: mechanism found
by David Turell , Friday, May 24, 2019, 15:28 (1791 days ago) @ David Turell
A specialized naturally existing membrane pump:
https://www.the-scientist.com/news-opinion/how-bacteria-become-drug-resistant-while-exp...
"A membrane pump found in most bacteria helps E. coli acquire drug resistance from neighboring cells even while they’re exposed to antibiotics, a new study shows.
"E coli is capable of synthesizing drug-resistant proteins even in the presence of antibiotics designed to cripple cell growth. That’s the finding by a group of French researchers reporting today (May 23) in Science. They also discovered how the bacteria manage this feat: a well-conserved membrane pump shuttles antibiotics out of the cell—just long enough to buy the cells time to receive DNA from neighbor cells that codes for a drug-resistant protein.
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"The team made an educated guess as to why the cells were capable of this: many bacterial membranes are known to harbor a multidrug efflux pump known as AcrAB-TolC, which is capable of shuttling a wide range of antibiotics out of cells, and the scientists figured that it was getting tetracycline out of the cell before it could stop protein synthesis and cell growth.
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"When functional, the AcrAB-TolC pump buys the bacteria time by keeping antibiotic concentrations just low enough for the cells to synthesize the resistance proteins encoded in the plasmid DNA, according to the researchers. In this case, it allows for the production of the TetA protein, which then shunts more tetracycline out of the cell. Ultimately, bacteria can become resistant while still under the influence of antibiotics.
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"The findings are widely relevant, she says—for one, because AcrAB-TolC is so broadly conserved across bacteria, and also because the mechanism is not limited to tetracycline. Lesterlin and his colleagues demonstrated that the pump also allows bacteria to produce drug-resistant proteins in the presence of other antibiotics designed to stifle gene expression, such as the translation-inhibiting chloramphenicol, and the transcription-inhibiting rifampicin. This mechanism is relevant for so-called bacteriostatic antibiotics, which don’t kill but only stifle bacterial growth, Lesterlin adds. He doubts it will work for bacteriolytic antibiotics, which destroy bacteria outright before they can become resistant."
Comment: for me the key point is that Tetracycline is an antibiotic that was found originally in nature as a natural defense molecule made by a fungus. Therefore what bacteria can do when presented with tetracycline is a defense mechanism for them that many of them developed at the beginning of evolution, just as they developed horizontal gene transfer. But note the final paragraph: we can analyze every bacterial mechanism that can be attacked and should be able to defeat resistance. Our first approach of finding natural antibiotics in soil has run its course.
Bacterial antibiotic new resistance: mechanism found
DAVID: ...for me the key point is that Tetracycline is an antibiotic that was found originally in nature as a natural defense molecule made by a fungus. Therefore what bacteria can do when presented with tetracycline is a defense mechanism for them that many of them developed at the beginning of evolution, just as they developed horizontal gene transfer. But note the final paragraph: we can analyze every bacterial mechanism that can be attacked and should be able to defeat resistance. Our first approach of finding natural antibiotics in soil has run its course.
So far, bacteria have found means of resisting just about everything that humans and Nature can throw at them. They simply use whatever materials are available to ensure their survival. Isn’t it strange that our highly developed intelligence is still unable to get the better of what some people believe to be unthinking automatons? Maybe they have a different form of intelligence from ours?
Bacterial antibiotic new resistance: mechanism found
by David Turell , Saturday, May 25, 2019, 16:33 (1790 days ago) @ dhw
DAVID: ...for me the key point is that Tetracycline is an antibiotic that was found originally in nature as a natural defense molecule made by a fungus. Therefore what bacteria can do when presented with tetracycline is a defense mechanism for them that many of them developed at the beginning of evolution, just as they developed horizontal gene transfer. But note the final paragraph: we can analyze every bacterial mechanism that can be attacked and should be able to defeat resistance. Our first approach of finding natural antibiotics in soil has run its course.
dhw: So far, bacteria have found means of resisting just about everything that humans and Nature can throw at them. They simply use whatever materials are available to ensure their survival. Isn’t it strange that our highly developed intelligence is still unable to get the better of what some people believe to be unthinking automatons? Maybe they have a different form of intelligence from ours?
Just perhaps it is the grand intelligence who first created them and gave them these automatic abilities?
Bacterial antibiotic new resistance: mechanism found
by David Turell , Tuesday, December 10, 2019, 00:36 (1591 days ago) @ David Turell
This is in a very dangerous enterococcus in immune depleted patients but lives in us normally without problem. It has automatic responses to drugs and our immune system:
https://phys.org/news/2019-12-achilles-heel-drug-resistant-superbug.html
"The research, published in the December issue of the Proceedings of the National Academy of Sciences of the United States of America, revealed that a protein called LiaX is released by bacteria into the environment to sense the presence of antibiotics, causing restructuring of the bacterial cell that prevents the drug from destroying it. VRE is on the Centers for Disease Control's latest threat report and is most commonly associated with health care settings. It can lead to serious complications, causing nearly 5,400 deaths in 2017 in the U.S.
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"Enterococci and other bacteria have a stress response system, called LiaFSR, which helps germs build drug resistance and adapt to many environmental stressors. LiaX, they discovered, is a major player in that system.
"'We call LiaX the master modulator of resistance, and it basically tells the bacteria to remodel their protective cell envelope, causing daptomycin to bind away from the septum and allowing the cell to survive," Khan said.
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"'We observed high levels of the protein outside of the cell that was binding to the antibiotic and signaling back to the cell to activate the stress response," Khan said.
In essence, the LiaX protein behaves like Paul Revere alerting the bacteria that the antibiotics are coming. However, the researchers discovered it's not just antibiotics that the protein can sense, it also signals when an immune response is happening.
"The immune system produces antimicrobial peptides, which are molecules that help fight infections caused by germs like bacteria or fungi. They work by destroying the cell envelope, much like daptomycin does.
"'What we revealed is that not only is LiaX acting as a sentinel protein that latches on to daptomycin, but it can sense the antimicrobial peptides created by our immune systems and elicit the same cell restructuring response," Khan said.
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"According to the researchers, a major takeaway from their study is not just that VRE produces a sentinel protein that can protect bacteria against antibiotics and the immune system, but that its protection inherently makes the bacteria more lethal during infection."
Comment: No thinking on the part of the enterococcus. Just automatically deploy the protein molecules
Bacterial antibiotic microbiome resistance: mechanism found
by David Turell , Thursday, March 05, 2020, 21:53 (1504 days ago) @ David Turell
Our necessary microbiome can protect itself when antibiotics are give to fight infection:
https://phys.org/news/2020-03-microbiome-species-interactions-reveal-bacteria.html
"';We found that interactions between species in the gut microbiome ecosystem influence the effectiveness of antibiotics at killing off an individual species within this community, as well as the entire community's metabolism," said Huang.
"The researchers demonstrated that when a type of bacterium from the fruit fly microbiome, called Lactobacillus—which are also found in yogurt—is grown together with a vinegar-producing fly bacterium called Acetobacter, it is less susceptible to death by antibiotics.
"This is a newfound category of a phenomenon called antibiotic tolerance, meaning that cells die much more slowly when found together than they would on their own. Tolerance can be dangerous, because this delay increases the risk that full-on resistance to the antibiotic could evolve.
"'Normally, tolerance occurs when a cell slows its metabolism in response to antibiotic exposure," explained Ludington. "But in this case, the tolerance is actually associated with increased metabolism."
"It turns out that the Acetobacters consume the lactic acid that is excreted as a waste product by neighboring Lactobacillus, providing a fitness advantage to both species and triggering the tolerance the team discovered.
"'We don't know exactly how it happens yet, but we think the two bacterial species both 'know' when the other type of cell is there and respond appropriately," said Benjamin Obadia of UC Berkeley. "These mechanisms are probably evolved from living together, and we wouldn't have seen them if we studied the two species in isolation.'"
Comment: My view is God started life with bacteria and they have been kept around to help us live better in many ways. Protection designed by God.
Bacterial antibiotic resistance: new mechanism found
by David Turell , Saturday, December 03, 2022, 18:41 (502 days ago) @ David Turell
In Streptococcus:
https://www.sciencealert.com/scientists-just-caught-bacteria-using-a-never-before-seen-...
"'This new form of resistance is undetectable under conditions routinely used in pathology laboratories, making it very hard for clinicians to prescribe antibiotics that will effectively treat the infection, potentially leading to very poor outcomes and even premature death," explains Telethon Kids Institute infectious disease researcher Timothy Barnett.
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"'Bacteria need to make their own folates to grow and, in turn, cause disease. Some antibiotics work by blocking this folate production to stop bacteria growing and treat the infection," explains Barnett.
"'When looking at an antibiotic commonly prescribed to treat Group A Strep skin infections, we found a mechanism of resistance where, for the first time ever, the bacteria demonstrated the ability to take folates directly from its human host when blocked from producing their own."
"So Streptococcus has been acquiring already processed folate from outside its own cells; these molecules are abundant in our bodies.
"The process completely bypasses the action of sulfamethoxazole, an antibiotic that inhibits folate synthesis within the bacteria, thus rendering the drug ineffective.
"Rodrigo and the team identified at least one gene involved: thfT. It encodes part of the folate harvesting system, not unlike our own, as we also can't produce folate and must get it from our food.
"Streptococcus bacteria with this gene, therefore, have found a way to suck up folate and subvert sulfamethoxazole.
"In the lab, Group A Streptococcus does succumb to sulfamethoxazole antibiotics because it doesn't have another accessible source of folate.
"In this case, the bacteria are only resistant to the antibiotics when they're causing an actual infection inside our bodies. This means there's no easy way of detecting this antibiotic resistance in pathology labs yet.
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"'Unfortunately, we suspect this is just the tip of the iceberg – we have identified this mechanism in Group A Strep, but it's likely it will be a broader issue across other bacterial pathogens," says Barnett.
"Understanding these mechanisms is the first step towards being able to test for them and counter them by prescribing other classes of antibiotics instead.
"'It is vital we stay one step ahead of the challenges of antimicrobial resistance and, as researchers, we should continue to explore how resistance develops in pathogens and design rapid accurate diagnostic methods and therapeutics," urges Rodrigo."
Comment: The battle continues. Here is dhw's wished for free-for-all. I think we will eventually win, as shown by recent research into chemicals that attack bacterial walls directly.