Showing posts with label antibiotics. Show all posts
Showing posts with label antibiotics. Show all posts

Monday, November 7, 2016

READ THIS BEFORE VOTING -- Presidential Science (WORLD) Issues!

Of the many unanswered questions that exist around the current election cycle, very few are as important than questions surrounding current scientific research and the funding for the future.



Why should the public vote/influence an increase in science funding?


Why do I suggest the importance of such research is so high?  


The range of issues that are tied to science funding is enormous.  Most people do not realize what issues are encompassed by science funding.  If you (the reader) are one that ties research funding only to important issues like - space or defense - then I ask you to please read everything below.  The reason is that the range of issues affected by science include climate science (flooding from Hurricane Matthew) to research into better treatments for eradicating the Zika Virus or Ebola Virus.



Additionally, what about the homeless problem that plagues the United States which includes many victims to serious mental health issues and impact the veterans among others roaming the streets without help.  Before you go to the voting polls tomorrow, please read the information below which might or might not influence your vote.  Either way, after reading the blog post below, you will definitely be better informed.  Last but not least, I will provide direct evidence of the wonderful job that artists such as Beyonce, Jay Z, and Leonardo DiCaprio are doing to elevate science and the need to get out and vote -- which is super inspirational.



Note: various words or phrases are hyperlinked to earlier posts on the subject or other research articles.  Please read widely and inform yourself on Science Issues.



Pending Issues Which Need To Be Addressed




Just look at the current state of affairs around the nation and the world along with the issues raised in the blog post below.  Then we can talk about the importance of such issues.  Currently, the entire East Coast of the United States is recovering from the dramatic flooding and winds which struck when Hurricane Matthew swept through and wreaked havoc on the region.



Any discussion of the funding for the destruction and the recovery?  



Has the East Coast rebuilt all of the damaged structures?  



Not in the least.  Why not?  If the same lack of attention toward science research into the issues exist today, where will we be as a nation in 4 or 8 years?  This is why the issues of science are serious and need to be entertained before we head to the voting polls next week.  At this point, you might be wondering the following question:


What are the most critical issues at hand that are associated with science for the candidates to express their views toward?



In a recent post, I simply cut and pasted the "Top 20 Questions from Science Debate" with the answers from the candidates.  The purpose was to give you (the reader) a sense of what the critical issues were through questions offered up by millions of scientist.  Those questions raised commentary within the scientific commentary within the community.  Below I offer a few articles which highlight the commentary from those questions.



A recent article from the website "BioscienceTechnology" titled "Coalition Presses US Presidential Candidates to Address Science Issues" offered commentary on the "Top 20 Questions" from the nonprofit organization "ScienceDebate."  The author chose to offer up six of the 20 questions as necessary to provide an example.  The six sample questions are shown below:



1) Many scientific advances require long-term investment to fund research over a period of longer than the two, four, or six year terms that govern political cycles. In the current climate of budgetary constraints, what are your science and engineering research priorities and how will you balance short-term versus long-term funding?
2) Mental illness is among the most painful and stigmatized diseases, and the National Institute of Mental Health estimates it costs America more than $300 billion per year. What will you do to reduce the human and economic costs of mental illness?
3) Strategic management of the US energy portfolio can have powerful economic, environmental and foreign policy impacts. How do you see the energy landscape evolving over the next 4 to 8 years, and, as President, what will your energy strategy be?
4) Public health efforts like smoking cessation, drunk driving laws, vaccination, and water fluoridation have improved health and productivity and save millions of lives. How would you improve federal research and our public health system to better protect Americans from emerging diseases and other public health threats, such as antibiotic resistant superbugs?
5) Science is essential to many of the laws and policies that keep Americans safe and secure. How would science inform your administration’s decisions to add, modify, or remove federal regulations, and how would you encourage a thriving business sector while protecting Americans vulnerable to public health and environmental threats?
6) Evidence from science is the surest basis for fair and just public policy, but that is predicated on the integrity of the evidence and of the scientific process used to produce it, which must be both transparent and free from political bias and pressure. How will you foster a culture of scientific transparency and accountability in government, while protecting scientists and federal agencies from political interference in their work?



The author seem to want to suggest that the above issues just did not impact science funding, but were of significance to the public at large.  I found the paragraph below fascinating:



“Some politicians think science issues are limited to simply things like the budget for NASA or NIH, and they fail to realize that a President’s attitude toward and decisions about science and research affect the public wellbeing, from the growth of our economy, to education, to public health,” Rush Hold, CEO of the American Association for the Advancement of Science, said in a prepared statement. He said that Americans should have the opportunity to know where Presidential candidates stand on these issues. 



All issues that are researched from a scientific standpoint are important.  Just because the public does not see the ramifications of such research does not disqualify funding.  Of course, there are certain areas that are of immediate importance than others.



Science Lessons For Next President




According to a recent article in the Journal "Science" titled "Science lessons for the next president" there are certain issues that need definite support.  Here is a short video of the issues stated succinctly (less than 4 minutes in length):







Below are the critical science lessons that are of upmost importance for the next President:



1) "Pathogens Change Faster Than Our Defenses"


Our ability to stay ahead of deadly pathogens relies on our ability to understand how to dismantle a virus or deadly bacteria.  I wrote a blog about new research that recently was uncovered in which scientists discovered a site (a part of the molecule) that is responsible for disabling the effectiveness of the antibiotic.  Meaning, if a target molecule hits this site, then the antibiotic is rendered ineffective (useless) and will not work.



More money should be devoted toward understanding and developing ways to counter that pathway toward disabling the antibiotic -- which is commonly termed as "Antibiotic Resistance."  Additionally, this relies on funding to develop drugs that will be effective and can be tuned to treat evolving pathogens.  In a blog post that I wrote recently, there was a short video outlining with an explanation the drug development process which is worth looking at and reading.  If you are still not convinced after reading the blogs, then read below the excerpt from the Journal 'Science' on critical issues which offers an alternative explanation of the importance of such research:



Importance:



Why it matters: Evolving pathogens can threaten our food and water supplies, natural resources, and health. In the United States, 2 million people develop antibiotic-resistant infections each year, and 23,000 die. Globally, the World Health Organization estimates that in 2015 there were 580,000 new cases of tuberculosis resistant to the two most powerful drugs used against this disease. Increasing drug resistance in malaria, HIV, and other major diseases threatens to undermine control efforts. And recently emerged threats, such as the Zika and Ebola viruses, are certain to evolve in ways that can be hard to predict. To develop treatments, scientists often must work with the most dangerous pathogens in laboratories, and sometimes even engineer new strains; this creates the possibility of accidental or intentional releases that could have dire consequences.


With the emergence of stories surrounding the spread of diseases throughout the world, research into these diseases is critical.  The issues above are due to evolving chemical systems that are natural and are constantly challenging us to keep ahead of the game to fight new pathogens.  If we switch gears and look at issues that are brought on by our own actions, we find challenges that definitely need to be addressed immediately.  One such issue is 'genetic engineering.'  The question is raised below:



What about potential problems brought by our own actions?



2)  "CRISPR Raises Tough Ethical Issues"



Recently, the field of 'genetic modification' has been getting alot of attention and rightly so.  The prospect of changing an organisms "genetic code" seems strange and straight out of a science fiction book.  Although, if I were to tell you that certain foods you eat have been genetically modified and you still love them -- what would you do?  Furthermore, if the so called 'genetic modification' was to help the crop avoid destruction -- i.e., preserve a given crop in order to provide you food, would your opinion change?  The current benchmark (among other methods) is the rising CRISPR-Cas9 method.  You can read more about the method on the 'Wikipedia' page if you wish.  In order to understand the importance of funding such research along with the potential implications, lets turn to the same article from the Journal 'Science' with the following explanation shown below:



Importance:


Why it matters: A powerful tool for basic research, CRISPR could also lead to new treatments for genetic disease in humans, pest-resistant crops with higher yields, and disease-resistant livestock. But uses of CRISPR could also raise profound ethical and regulatory concerns. It could allow the creation of human embryos with modified genes in their germ line—eggs and sperm—meaning the changes would be passed on to future generations. And, in an approach known as gene drive, CRISPR could be used to permanently alter the genome of an entire species in ways that could shift its evolutionary path and ecological role, or even wipe it off Earth. In principle, gene drive could give an endangered species a boost, wreck the genetic defenses that allow some weeds to resist herbicides, or drive a disease-carrying mosquito to extinction.




The promises are huge as well as the payoffs if the CRISPR method is perfected.  And I say "perfected" -- why?  Because, according to a certain part of the science community, the method does not work "perfectly."  Professor Karmella Haynes at Arizona State University is performing research that investigates which environments where the CRISPR method works well.  The method does not work well in human embryo cells.  The DNA is coiled differently (slightly as a defense mechanism) which presents a large challenge.  Of course, in the popular science news, positive results are published rather than discouraging results.  Nonetheless, the method is still a strong method.



As an example, here is a short video of a reporter trying to perform the CRISPR method and failing shown below:







The above video shows the extent to which science is a profession of tireless effort.  Time is put into get results and verify the methodology of a given experiment.  Often, people think that scientists have an easy job -- but in fact, the development of research that is reproducible and clear to the public is a difficult task which takes time and money.



Certain areas require more time than others to delve into a given research inquiry.  How about the atmosphere?  The time scale of global warming is seemingly long.  Although, according to current reports, action is needed immediately.  The danger associated with the lack of immediate action is catastrophic.  I find the fact that certain politicians are in denial a terrible observation and can only exacerbate the problem and solution.



3)  "Sea Levels Rising"



As a nation, the United States public has been engulfed by the current chatter on the television along with the myriad devices that each of us carry around.  Not too long ago, their were three presidential debates.  Did you watch the debates?  Were you able to watch the debates?  Why do I ask such questions?



Because, while some were watching the debates, other East Coast residents were in the midst of cleaning up their lives which were ripped apart by Hurricane Matthew.  The depth of the destruction along with the cost of the damage to the U.S. has not yet been realized.  What is realized is that there have been some crazy weather patterns lately.  Further, the seas have been rising.  Both situations are not good indicators for the future.   The amount of rain that dropped during Hurricane Matthew was insane compared to other large storms around the globe.  You can read about the comparison here.



In order to fully understand the importance of such rising sea levels, lets turn to the article (series) we have been citing about the six lessons for the next president.  Here is the "importance" stated below:



Importance:



Why it matters: Nearly 40% of the U.S. population lives near the coast, and shorelines host extensive infrastructure—including roads, rail lines, ports, military bases, and energy, water, and sewer plants—that will cost billions of dollars to protect or replace. Already, shorefront communities in hot spots of sea level rise, such as Hampton Roads, Virginia, and Miami Beach, Florida, are seeing tidal floods—even on sunny days—that clog traffic, poison lawns, and corrode utilities. Key ecosystems are also at risk of inundation, such as wetlands and aquatic grass beds that help protect coastlines from storms and provide important nursery grounds for economically important fish. This rising stage also allows stormwaters to surge deeper and higher inland, exacerbating their damage.



Based on the destruction that we have seen this year in the United States as a result of a rising sea level (flooding rain), there is no question that the above research is vitally important.  One candidate (Donald Trump) would like to take funds away from research concerning global warming and fight ISIS.  Ask yourself if this is a good idea?  Is that where you want your money spent?  Money is already available for the Department of Defense for such adventures.  If any money should be diverted toward research in defense, then how about toward mental health for veterans returning from war with invisible wounds?



4)  "Brain Health Should Be Top Of Mind"



Dr. James Watson once posed the following question regarding the human brain:



Can the brain understand itself?



The above question at first sight appears to be quite simple.  Yet, over the decades that have past coupled with the advancing digital age, science still appears to be in the dark age to an extent.  At the other end of this logic, the computational power needed to understand the brain is said to not yet exist.  If the second statement is correct, then we need not stop funding research just yet.



Each and every one of us has either experienced or been touched by a person with a mental health issue.  Even if we did not realize it at the time.  Mental health is an extremely complicated issue that plagues parts of the entire population from the homeless to the ultra rich.  Mental Illness is blind to income and wealth.  With the new initiative to study the brain put forth by President Obama, we are headed in the correct direction.  He has the BRAIN initiative - which can be understood in greater detail by reading more about here.  Why is the health of the brain so important?  Here is an excerpt from the article in 'Science' below:



Importance:



Why it matters: Brain health touches us from cradle to grave, and when brain disease strikes, the costs—personal and budgetary—are staggering. By 2025, at least 7 million Americans are expected to suffer from Alzheimer's disease, which causes memory loss, personality changes, impaired reasoning, and, eventually, death. This year alone, treating and caring for Americans with Alzheimer's and other less common dementias cost $236 billion, with government health programs shouldering two-thirds of the cost. At the other end of life, the prevalence of autism, a disorder of language and social communication, rose by 123% between 2002 and 2012. That year, one in 68 U.S. children was affected; costs to each affected family are estimated at about $60,000 annually.

Other brain health issues abound. Learning disabilities are a big issue in classrooms; mental illness is common in the homeless, in addicts, and in prison inmates; and concussions have become a major concern in sports. The military faces the burden of treating traumatic brain injuries and the psychological aftereffects of combat. Effective diagnostics and treatments could make a huge difference.



As I mentioned above, the amount of computational power needed to fully understand the brain is just being realized.  Think about current research just published which shed light on the way proteins behave in their natural environment -- inside a human cell.  If research carried out at the current level sheds light on the onset of diseases, then imagine the requirement to understand diseases inside the entire brain (different parts of the brain acting together).  The point is that research into the disease causing aspects of the brain as well as our ability to comprehend the world around us is extremely important.



With the rise of the machine in understanding the world around us come other advances of the same technology.  Artificial intelligence has been speculated to be around and supposedly proposed to play a large role in our lives in the coming decades.  For now, what about simple machines -- drones? self driving cars, etc?



5) "Machines Are Getting Much, Much Smarter"



Elon Musk has been in the news lately for a variety of reasons.  His space initiative has cost the private sector of the space industry a pretty penny.  He has shown a complete lack of regard for the loss of life in his Tesla cars while operating on autopilot.  How?  He cannot admit that his technology is not nearly where technology needs to be at in order to let everyone have an autonomous car.  I write about this here.   In order to have completely autonomous cars, advancements in artificial intelligence will have to be taken toward a whole new level.  Currently, we are not there yet.  Science can shed light on potential issues that prevent us from proceeding to 'go' just yet -- which are shown below:



Importance:



Why it matters: Although experts say we are still decades away from machines that truly think like humans, narrower applications of AI are already having an impact on society. Products and services from self-driving cars to systems that guide medical care and treatment could bring major benefits, including increased labor productivity, lucrative new markets, and fewer deaths from traffic accidents and medical mistakes. But AI brings worries, too. It will enable employers to automate more tasks and displace workers, and economists predict that some low-wage jobs will be among the first to be eliminated, possibly increasing economic inequality. Letting machines make their own decisions also raises profound ethical, legal, and regulatory questions. Who is responsible if an autonomous car crashes, a piece of software wrecks an investment portfolio, or a sensor switches a stoplight to green at the wrong time? The stakes are even higher on the battlefield, where the military is exploring the possibility of fielding autonomous lethal weapons that would make their own decisions about when to fire.



Advancing forward, a fair amount of research needs to be conducted.  From the machine programming and execution standpoint, current research is quite advanced.  Just this week, research about a world record was set for NASA surrounding the precision of a satellite with GPS technology.  A satellite traveling at a distance of 43,500 miles travels the slowest, whereas at a distance of just under 5 miles from Planet Earth -- the satellite can travel at speeds of 22,000 miles per hour.  The precision offered in orbit has allowed very precise 3-dimensional images of different aspects of Earth.  This is just one of many reasons why space funding is extremely important.  Better precision, better time, new technologies.



Although, with space research comes risk.  Over the decades, risk has been studied and worked on by scientists over various scales within various problems.  From the small scale - quantum error correction to the enormous scale of space flight - risk remains a crucial area of need to study in greater detail.



6) "We Aren't So Great At Assessing Risk"



Communicating risk to the public without posing great fear is extremely complicated.  In many areas of research, communication of results is equated with great fear surrounding the research which leads to reductions in funding and possible cancellations of investigations all together.  This highlights the demand to understand how to greater understand risk and the ability to convey risk to the greater public.  Two areas seem to be polarized with regard to risk: 'genetic engineering' and 'climate change'.  These two areas stand at opposite ends of the spectrum, but are equally important.  In the area of 'genetic engineering' - the scare lies in the unknown product and effect toward civilization.  Whereas in the other area -- climate science, the scare lies in the incomprehensible.  Thinking on the global scale couple with temperatures rising to the point of civilization not being able to occupy the Earth is unfathomable and science fiction -- as far as some are concerned.



Therefore, understanding how to communicate and assess risk is crucial.  Science says:



Importance:



Why it matters: Misperception of risk can push a president to overreact to lesser threats and underreact to greater problems, or to embrace policies that may make people feel good but end up being costly and ineffective—or even counterproductive. And how a president communicates with the public about risk can mean the difference between sowing panic and maintaining calm. Talking realistically about risks in advance—as opposed to promising absolute protection—may help prepare people for the inevitable disasters and minimize calls for a policy response that's out of proportion to the actual threat. To do this effectively, the president will have to maintain the public's trust, which is much harder to earn than it is to lose. Understanding the basic psychology of risk can help avoid missteps.


Again, transmitting the unfathomable to the public is complicated.  The best hope is that the communicator is a good communicator (patient, humble, and intelligent) with a great audience (patient, humble, and intelligent).  Yes, each of us need to do our part to achieve transmission of information (i.e. communication) between one another.  Hollywood does this quite well.  Science is a work in progress.



Celebrities Elevate STEM and Voting!




Beyonce (the singer) recently promoted the presidential candidate Hillary Clinton along with her husband Jay Z.  With good reason.  It has taken over a hundred years to achieve equality (and we are still fighting for it) - a work in progress.  Having the first female president would be a major step in the right direction.  Furthermore, this would reinforce the idea that any woman can go as far as she is willing to work to go.  My wife is a scientist and I encourage her to be the best she can be -- break all barriers.



Although, the fields -- Science Technology, Engineering, and Mathematics (STEM) still need more women and minorities engaging in them for careers.  Each of us is smart in our own unique way.  There are plenty of women and minorities out there to help take science and society to the next advanced level.  Having celebrities elevate science is critical.  Science usually gets a bad rap.  Why?  Movie portrayals (such as "The Accountant") portray scientists as strange with disorders but super smart.  Not all are strange.  I promise.



Recently, the actor Leonardo DiCaprio became the 'Messenger of Peace' for the United Nations -- an honor he holds dearly and sincerely.  He speaks about the role in a documentary he recently released investigating the state of global warming and explored all possible solutions.  We need more people like him with the unparalleled ability to communicate to a large audience the importance of research and world problems.  Here is the video below (just over an hour and a half in length) - but worth watching before or after the election:








I think that I have provided you (the reader) with an eyeball full of information to think about before you hit the voting polls. Get out and vote. Listen to the stars, listen to your family, just be sure to vote. Exercise your place in our democratic society. Yes, your vote does count.



Conclusion ...



Science funding impacts all areas of our lives.  If you do not believe me, just try to think of an area which has nothing to do with science.  Leave the answer in the comments below and I will try to provide a rebuttal to your answer.  There is no rebuttal for the issues that can be solved with science but lack funding.  We need all of the help that is possible to educate the public about the importance of science.  How do you help?



The most important learning begins at home.  What about science do you not understand?  Why don't you care?  What kind of world are you leaving to your children?  These questions do have answers.  The unknown is centered around how those answers will surface in the days and years to come.  Whether we find out the answers through your vote, your children, your family, the answers will become apparent.  Why not educate yourself and others on critical issues for a better society?



I hope that each of you go out and vote tomorrow. Further, I hope that each of you are inspired to educate yourself more after reading this post.  Until next time, Have a great day!!!












Wednesday, October 12, 2016

Unraveling The Resistance Of Antibiotics!

Stories seem to emerge daily regarding the threat to the human race regarding the rise in resistance of antibiotics toward common diseases.  One side of the spectrum, the pro-antibiotic sector are dispersing antibiotics like candy to farm animals and patients without caution.  Whereas on the other side of the spectrum, there is a growing community of researchers, advocates, and concerned citizens -- yelling at the top of their voices to stop administering antibiotics needlessly.  With both sides of the spectrum known, the following question emerges naturally:



Where is scientific research at on the issue?



Are advancements in discovery being made to deal with the potential threat?



The short answer is that the discovery process takes time and is complicated.  Which is no answer at all.  Whereas the long term solution involves research being done.  As I explained in a previous post on drug discovery, research advances are arduous and take time.  Recently, though, progress has been reported in the scientific community and worth giving a "shout out" about.  Below is the short post regarding the advance.



Antibiotic Resistance?




Yes, whenever I hear about antibiotic resistance, I stop and pause for a moment of scare.  Then I think about the progress that is being made (hopefully).  I cannot have myself worry too much about the issue since I do not perform research directly toward a solution.  Although, I can support students who are biochemistry undergraduates and graduate students while educating them on the need and importance of such research.  Couple that with a proper training on the scientific instrument needed to perform the research and my job ends there.



Sounds scary right?



Well, not all is held in limbo with regard to antibiotic resistance.



First, what is antibiotic resistance?  In order to understand the issue, what is the problem?



Here is an excerpt taken from the 'Wikipedia' page for "Antibiotic Resistance" is shown below:



Antimicrobial resistance (AMR) is the ability of a microbe to resist the effects of medication previously used to treat them.[2][3][4] This broader term also covers antibiotic resistance, which applies to bacteria and antibiotics.[3] Resistance arises through one of three ways: natural resistance in certain types of bacteria; genetic mutation; or by one species acquiring resistance from another.[5] Resistance can appear spontaneously because of random mutations; or more commonly following gradual buildup over time, and because of misuse of antibiotics or antimicrobials.[6] Resistant microbes are increasingly difficult to treat, requiring alternative medications or higher doses—which may be more costly or more toxic. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR); or sometimes superbugs.[7] Antimicrobial resistance is on the rise with millions of deaths every year.[8] A few infections are now completely untreatable because of resistance. All classes of microbes develop resistance (fungi, antifungal resistance; viruses, antiviral resistance; protozoa, antiprotozoal resistance; bacteria, antibiotic resistance).
Antibiotics should only be used when needed as prescribed by health professionals.[9] The prescriber should closely adhere to the five rights of drug administration: the right patient, the right drug, the right dose, the right route, and the right time.[10] Narrow-spectrum antibiotics are preferred over broad-spectrum antibiotics when possible, as effectively and accurately targeting specific organisms is less likely to cause resistance.[11] Cultures should be taken before treatment when indicated and treatment potentially changed based on the susceptibility report.[12][13] For people who take these medications at home, education about proper use is essential. Health care providers can minimize spread of resistant infections by use of proper sanitation: including handwashing and disinfecting between patients; and should encourage the same of the patient, visitors, and family members.[12]
Rising drug resistance can be attributed to three causes use of antibiotics: in the human population; in the animal population; and spread of resistant strains between human or non-human sources.[6] Antibiotics increase selective pressure in bacterial populations, causing vulnerable bacteria to die—this increases the percentage of resistant bacteria which continue growing. With resistance to antibiotics becoming more common there is greater need for alternative treatments. Calls for new antibiotic therapies have been issued, but new drug-development is becoming rarer.[14] There are multiple national and international monitoring programs for drug-resistant threats. Examples of drug-resistant bacteria included in this program are: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), extended spectrum beta-lactamase (ESBL), vancomycin-resistant Enterococcus (VRE), multidrug-resistant A. baumannii (MRAB).[15]
A World Health Organization (WHO) report released April 2014 stated, "this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance—when bacteria change so antibiotics no longer work in people who need them to treat infections—is now a major threat to public health."[16] Increasing public calls for global collective action to address the threat include proposals for international treaties on antimicrobial resistance.[17] Worldwide antibiotic resistance is not fully mapped, but poorer countries with weak healthcare systems are more affected.[9] According to the Centers for Disease Control and Prevention: "Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections." [18]



Is that a comprehensive definition?



Instead, why not start with a simple pictorial representation of what antimicrobial resistance is.  In a previous post on the need for greater science communication, Dr. Tyler Dewitt gave a great explanation of the modes of how virus's and bacteria invade a host organism like the human body.  I suggest taking a look at the post.  Once the invader (virus or bacteria) enters the system, the invader takes hold (control) of your system.  The control allows the invader to make several copies of itself to proliferate and grow to become a problem (onset of disease).



What can be done about such a state?



One methodology that has become increasingly common if the invader is a microbe or bacteria is to administer antibiotics which wipe out the infection.  Shown below is a picture taken from the 'Wikipedia' page again for clarity to illustrate the point of action of antibiotics:




Source:By NIAID – NIH



The image above is very simple to understand the action of an antibiotic.




Advances In Antibiotic Resistance




Recently, there has been advances in research surrounding antibiotic resistance that may speed up the ability to deal with the looming threat.  In an article from the website 'Sciencedaily.com' titled "Mystery of bacteria's antibiotic resistance unravelled" new developments have been made in unraveling the mode of disabling the effect of antibiotics by researchers.  Here is an excerpt discussing the advancement:



One of the mechanisms leading to rifampicin's resistance is the action of the enzyme Rifampicin monooxygenase.

Pablo Sobrado, a professor of biochemistry in the College of Agriculture and Life Sciences, and his team used a special technique called X-ray crystallography to describe the structure of this enzyme. They also reported the biochemical studies that allow them to determine the mechanisms by which the enzyme deactivates this important antibiotic.

The results were published in the Journal of Biological Chemistry and PLOS One, respectively.

"In collaboration with Professor Jack Tanner at the University of Missouri and his postdoc, Dr. Li-Kai Liu, we have solved the structure of the enzyme bound to the antibiotic," said Sobrado, who is affiliated with the Fralin Life Science Institute and the Virginia Tech Center for Drug Discovery. "The work by Heba, a visiting graduate student from Egypt, has provided detailed information about the mechanism of action and about the family of enzymes that this enzyme belongs to. This is all-important for drug design."


 Before I make a few comments on the success of the discovery in the pipeline to a marketable drug or treatment, I would like to add another excerpt from the same article highlighting the importance of the antibiotic rifampicin is to an array of diseases:



Rifampicin, also known as Rifampin, has been used to treat bacterial infections for more than 40 years. It works by preventing the bacteria from making RNA, a step necessary for growth.

The enzyme, Rifampicin monooxygenase, is a flavoenzyme -- a family of enzymes that catalyze chemical reactions that are essential for microbial survival. These latest findings represent the first detailed biochemical characterization of a flavoenzyme involved in antibiotic resistance, according to the authors.

Tuberculosis, leprosy, and Legionnaire's disease are infections caused by different species of bacteria. While treatable, the diseases pose a threat to children, the elderly, people in developing countries without access to adequate health care, and people with compromised immune systems.



As you can see, the ability of the antibiotic rifampicin to knock out an array of important diseases cannot be overstated.  Therefore, any advancement in understanding modes of action or in this case 'inaction' are critical to drug designers for the future.  At this point, you might be wondering what the structure of rifampicin looks like?  Shown below is the chemical structure of rifampicin take from 'Wikipedia':




Rifampicin

Source of image: By Vaccinationist - Rifampicin on PubChem



With the discovery of the mechanism by which Rifampicin Monooxygenase deactivates rifampicin's ability to act as an antibiotic, should we all throw our hands up and celebrate?



The discovery of the deactivation mechanism of rifampicin is a major step for drug makers in producing new lines of antibiotics in the future.  As I mentioned in a previous blog on drug discovery, the flow of patentable drug includes discoveries made at the university level.  This discovery certainly qualifies as one -- certainly.  Although, more studies will have to be followed up in order to realize the discovery into a better antibiotic in the future.



I should mention one major point of contention about the discovery of the mechanism.  The spectroscopic technique that was used was x-ray crystallography.   X-ray crystallography as a technique just celebrated it't 100th year since the discovery of the technique.  Here is an excerpt from the 'Wikipedia' page describing the technique of 'x-ray crystallography':



X-ray crystallography is a tool used for identifying the atomic and molecular structure of a crystal, in which the crystalline atoms cause a beam of incident X-rays to diffract into many specific directions. By measuring the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture of the density of electrons within the crystal. From this electron density, the mean positions of the atoms in the crystal can be determined, as well as their chemical bonds, their disorder and various other information.
Since many materials can form crystals—such as salts, metals, minerals, semiconductors, as well as various inorganic, organic and biological molecules—X-ray crystallography has been fundamental in the development of many scientific fields. In its first decades of use, this method determined the size of atoms, the lengths and types of chemical bonds, and the atomic-scale differences among various materials, especially minerals and alloys. The method also revealed the structure and function of many biological molecules, including vitamins, drugs, proteins and nucleic acids such as DNA. X-ray crystallography is still the chief method for characterizing the atomic structure of new materials and in discerning materials that appear similar by other experiments. X-ray crystal structures can also account for unusual electronic or elastic properties of a material, shed light on chemical interactions and processes, or serve as the basis for designing pharmaceuticals against diseases.



The spectroscopic technique is very powerful and is commonly used in a wide range of areas of research for structural determination.  One drawback is the constraint of having to grow a crystal -- a rather large crystal to subject the x-rays to in order to obtain a diffraction pattern.



Why does this matter?



One commonly held belief among spectroscopists is that x-ray crystallography is extremely useful in a range of areas as a first step or a confirmation step.  The constraint of having to grow a crystal is also a large point of contention regarding the usefulness of the information obtained by the diffraction pattern.  Why?



The reason is centered around the fact that processes in the body (i.e., at physiological conditions) are performed in a 'liquid-state' rather than a 'crystalline-state' (i.e., solid state).  Scientists argue about the true degree of accuracy of a structure obtained by x-ray crystallography rather than say a structure obtained by nuclear magnetic resonance (NMR) in the liquid state.  The structure obtained by NMR is believed to be more representative of the actual conditions (liquid state, pH, temperature, etc.).



Nevertheless, the discovery above is extremely important.  The realization of a site of deactivation for rifampicin monooxygenase can now be further explored and compared to other antibiotics.  Scientists in industry and academia (university settings) will use incorporate this mechanism into their current understanding and models to produce a better antibiotic.



Further, understanding 'antimicrobial resistance' is a hot topic.  Just today, the 'Los Angeles Times' published an editorial discussing two bills that are hitting legislature for consideration.  Lets hope the combined efforts of all of these actions, leads to fewer cases of deaths in hospitals along with safer and better antibiotics.


Conclusion...




Should we be celebrating?


The advancement discussed above is cause to celebrate momentarily. Although, as I mentioned in the previous post regarding the drug discovery process, the path is long and arduous. Advancements such as these improve the ability of researchers to add another piece to the puzzle. Given more information, further advances can be pushed even further. Of course, that goes without being said (i.e., thank you captain obvious). Research is a long process and needs a lot of funding and time to test and retest procedures to make sure that scientists get the process right -- to eliminate the problem the first time around. Adjustments often have to be made due to inefficiencies of a given treatment or terrible side effects. Although, with a better understanding of the mode of action and inaction, drug manufacturers create more accurate drugs and research is one step further in understanding how nature operates to take control over our immune systems or subject us to terrible diseases.



Last but not least, the overall importance of writing a post like this is to convey the excitement and importance of such research. To demystify the meaning of "antibiotic resistance" or "antimicrobial resistance." Raising awareness of the magnitude of the issue will hopefully rally support on part of the public (your support) to elevate the need for funding and research into such issues. Do your part. Advocate for science and educate yourself on the successes and challenges (failures, obstacles). Give us some feedback.


Until next time, have a wonderful day!