IBM's Nano Approach to Killing Drug Resistant Bacteria

Chemists at IBM Research have been working to create "ninja polymers" that can target MRSA-infected cells in the human body and destroy their harmful payload.

Bacteria such as methicillin-resistant staphylococcus aureus (MRSA) are resistant to commonly-used antibiotics. IBM has drawing upon its experiences with semiconductor technology to create antibiotic-free bacteria killers. While they were researching ways to etch silicon wafers at a smaller scale than currently possible, they found some materials that could produce an electrostatic charge when chained together to form a polymer.

When these "ninja polymers" are introduced to the bloodstream, they self-assemble into biocompatible nanostructures that are electrostatically drawn to infected cells while not affecting healthy ones. When the reach those cells, they destroy the bacteria and then biodegrade with no side effects or accumulation within the body. Because the attack is physical, rather than chemical, the bacteria are les likely to be able to build up resistance to it.

These sticky nanostructures work in a very different way to antibiotics, according topolymer chemist Jim Hedrick. "They try to mimic what the immune system does: the polymer attaches to the bacteria's membrane and then facilitates destabilisation of the membrane. It falls apart, everything falls out and there's little opportunity for it to develop resistance to these polymers."

In addition to being useful vehicles for the delivery of drugs, these polymers could also be added to every day cleaning solutions. The research team believes that they could be used to replace the widespread distribution of antimicrobial agents found in hand gels, antibacterial wipes, toothpaste and even socks. _Wired

An earlier description of this research

There are a number of physical approaches to attacking drug-resistant bacteria, which are less likely to induce bacterial resistance -- including metal ions such as silver and titanium.

Nanotechnological materials research is likely to discover large numbers of other physical approaches to destroying drug resistant bacteria before they can spread.

WHO Says Super-Clap Wants You!

The World Health Organisation (WHO) recently sounded an alert on the spread of drug resistant gonorrhea in Japan, Australia, and Europe. More on the spread of the superbug across Europe:

"Superbug" strains of gonorrhea which are becoming untreatable accounted for almost one in 10 cases of the sexually transmitted disease in Europe in 2010, more than double the rate of the year before, health officials said on Monday.

The drug-resistant strains are also spreading fast across the continent, officials warned. They were found in 17 European countries in 2010, seven more than in the previous year. _ChiTrib

The US CDC recently held a Grand Rounds on the topic of the growing threat of multi-drug resistant gonorrhea (see video below).



Lost in all the PC-tainted publicity, are the details of where the drug resistant strains are coming from, and the nature of the populations which are affected.

If multi-drug resistant have started popping up in the past few years in Japan, Australia, and Europe, where were these microbes found before that? In Sub-Saharan Africa.

This study illustrates the high frequency of resistant gonococci in Africa and shows that tetracycline-resistant N. gonorrhoeae have become highly endemic in different geographic areas of the continent. The use of effective drugs is essential to reduce gonorrhea transmission. Surveillance of temporal changes in antimicrobial resistance in gonococcal strain populations should be part of sexually transmitted diseases control programs. _STD Jan 1997

Over the years, the microbes developed resistance to more and more antibiotics, so that now some strains of super-clap are resistant to virtually all commonly available antibiotics.

We know that STDs (including HIV) are running particularly rampant in African American populations, in Sub-Saharan (SS) Africa, and in all populations of the SS African diaspora. It only took a few years for HIV to spread from Africa to Haiti and to gay communities across the developed world.

We are told that super-gonorrhea is spreading rapidly throughout Europe. But so are African immigrants. Perhaps the news stories should divulge the nature of the populations in Europe which are particularly affected? That would be much more helpful to the public than current news stories, which neglect to inform the public of such crucial information.

People of SS African descent suffer from a wide variety of problems, including low average intelligence, high rates of violence, high rates of poverty, high rates of illegitimacy, and high rates of a wide range of infectious and degenerative diseases. The last thing that this community needs is to be "protected and shielded" by PC journalists and politicians, to the point of not understanding the serious threats its people are facing.

Gonorrhea is often asymptomatic, and often the symptoms are ignored without seeking treatment. When the disease is treated, it is often undertreated -- either due to medical error, lack of adequate drug supply, or due to the patient's own neglect in skipping doses or discontinuing the treatment too soon.

Complications of inadequately treated gonorrhea include neonatal blindness, often fatal ruptured tubal pregnancy, long term painful pelvic inflammation, scarring of pelvic tissues leading to infertility, and more.

The problem of bacterial drug resistance is not limited to STDs such as gonorrhea. Multi-drug resistant TB is an even greater threat than gonorrhea, in terms of potential loss of life.

While no populations are immune to such diseases, particular populations are in more danger than others. Prison populations, for example, can be more exposed to a wide range of infectious diseases, depending upon the conditions of the prisons. Infectious disease spread by sexual contact, airborne spread, and contact with fomites, can all be more common in many prison populations -- particularly in the third world.

There are many ingenious research plans for dealing with multi-drug resistant microbes. But it takes a long time for ideas to progress through the many stages of research into common clinical usage. The process of treatment research and development is also very expensive. When research pioneers are trying to break through one or more common paradigms of standard medical treatment, the delays can stretch even longer.

Be careful out there.

Antibiotic Booster Adjuvants: Allies in Fight Against Resistant Bacteria

As drug-resistant bacteria continue to challenge the existing armamentarium of antibiotics and scant new options emerge from the pipeline, scientists and clinicians are exploring a new strategy that may make existing drugs more effective and prevent new resistant strains from emerging.

They are seeking so-called antibiotic adjuvants. Just like adjuvants used for improving the immunogenicity of vaccines, these compounds enhance the action of antibiotics. They may do so through a variety of mechanisms, including by weakening the bacteria themselves, making them more vulnerable to antibiotics, or by interfering with bacterial mechanisms of antibiotic resistance. Teams working in this area have recently published or presented work highlighting promising antibiotic adjuvants—some found among drugs currently used for other applications, others derived from compounds in ocean environments. _JAMA

Anti-Diarrheal Drug Loperamide Boosts Minocycline Potency

Combining common antibiotics with additional compounds could make previously resistant bacteria more susceptible to the same antibiotics. ‘Resuscitation’ of existing antibiotics has the potential to make infections caused by multidrug-resistant bacteria easier to control, reducing antibiotic usage and levels of antimicrobial resistance, say scientists presenting their work at the Society for General Microbiology’s Spring Conference in Dublin this week.

Researchers from University College Dublin (UCD) studied a variety of bacteria that are frequently associated with hospital-acquired infections, including Pseudomonas, Klebsiella, Enterobacter and Staphylococcus. Bacterial samples were collected from hospital patients and from these, strains that showed resistance to a commonly prescribed antibiotic – ciprofloxacin - were selected for study.

The team tested ciprofloxacin in combination with one of five different ‘adjuvant’ compounds against these bacteria, to determine which combinations, if any, were more effective than treatment with ciprofloxacin alone. Results showed that all five adjuvant compounds increased the efficacy of ciprofloxacin; making it more active against the bacteria by up to six-fold. .

...The team believes that adjuvant therapy could revolutionize the way that antibiotics are used nowadays. “Hopefully this work will allow antibiotics to be incorporated into treatment regimes and administered in more effective ways,” said Dr Martins. “As well as extending the lifespan of current antibiotics, this approach could ultimately reduce levels of antimicrobial resistance in hospitals as well as in the community, allowing hard-to-treat bacterial infections to be successfully controlled,” she said. _SGMNews_via_SD

From the abstract of a Feb 2011 paper:

The absence of new antibiotics has led to a growing reliance on older, more toxic drugs such as colistin, but resistance to these is already arising. One approach to combat this growing problem is the use of combination drug antibiotic adjuvant therapy, which potentiates the activity of antibiotics....Adjuvant therapies include antibiotic combinations, synergy between antibiotics and nonantibiotics, inhibition of resistance and molecules that alter the physiology of antibiotic-insensitive cells, such as those in biofilms.... _NIHPubmed

The combination drug Augmentin can be consider as a forerunner of this new class of combination, anti-resistance antibiotics. The clavulinic acid in augmentin blocks a penicillinase enzyme that would otherwise inactivate the amoxicillin antibiotic.

As stated previously on Al Fin, bacteria are shifty, but humans have brains. Perhaps the global increase in antibiotic multi-resistance will spur more humans to use the brains they have to find solutions to the problem.

Humans vs. Bacteria: An Unfair Advantage?

There is an arms race between humans and bacteria. My opinion for decades now, has been that the human brain gives humans the long term advantage in this race. Here is more detail on an approach to fight bacterial resistance that I alluded to in an earlier post:

In 2005, biochemist Floyd Romesberg of the Scripps Research Institute, near San Diego, announced that his lab had discovered a gene called LexA that switches on the error-prone DNA, enabling the microbe to mutate rapidly.

Shortly before this announcement, Romesberg presented some startling findings during a meeting at the institute I cofounded, the BioAgenda Institute. Romesberg, a short, intense man with a graying beard and an ability to explain complex ideas to nonscientists, told us that his lab had learned how to turn off LexA. Several major biotechnology figures at the meeting said to me, "This is huge." At the time, several top-tier venture-capital firms were vying for Romesberg's attention in hopes of starting a company. Ned David was one of the lucky cofounders who later named the company Achaogen--"achao" means "against chaos" in Latin.

Now Romesberg has announced the discovery of a molecule that inhibits LexA'sability to cause mutations; it was found after the lab screened more than 100,000 possible compounds. The molecule also slips easily into a bacterial cell, which is critical to creating an effective tool to zap the bugs.

This new mutation killer does not prevent bacterial infections. Taken in combination with antibiotics, it would prevent the bugs from mutating in response to the antibiotics, thereby preventing resistant strains from developing. The drug could also be used to restore the effectiveness of older antibiotics that have been rendered almost useless by bacterial resistance.

Source

I particularly like the idea of restoring efficacy to older antibiotics--since those tried and true drugs are much less expensive than the newer "uber-antibiotics."

Using bacterial cell signaling proteins as drug targets is logical, and much easier with modern lab techniques. It is the current explosion of discovery in the biological sciences--combined with bioinformatics software AND proper economic incentives--that will change the face of medical treatment. This revolution will happen in the developed world and in the third world, thanks to the generosity of the people of western nations.


Perhaps the idea of western aid to impoverished and underdeveloped nations originated in the protestand missionaries of the 18th, 19th, and 20th centuries. But now the concept is thoroughly secularized and mainstreamed in the west.

Contrast the many billions of dollars of private aid from western organisations with muslim "aid" from wealthy oil states that is oriented toward spreading violent islamism around the world. Russian and Chinese "aid" is oriented toward strategic alliances and natural resources of the third world. In contrast, the many private, non-state organisation of the western world generally try to address the most serious humanitarian problems. Often this effort is opposed by the dictatorships and other political entities that cause most of the hardship in the first place.

Bacteria are Shifty, But Humans have Brains and May Learn to Use Them Eventually

Drug resistant bacteria may kill over 100,000 North Americans each year. Particularly worrisome at this time are drug resistant staph and TB. The traditional pharmacological approach to the problem has been to develop new classes of antibiotic drugs, or to modify existing drugs to combat bacterial resistance. That approach is both expensive and not clever--more the brute force approach. Occasionally the rare innovative thinker comes up with an alternative, more lateral approach.

A new antimicrobial approach can kill bacteria in laboratory experiments and eliminate life-threatening infections in mice by interfering with a key bacterial nutrient, according to research led by a University of Washington scientist. The joint project, conducted at the UW, the University of Iowa, and the University of Cincinnati, will be featured in the April 2 issue of the Journal of Clinical Investigation.

Bacteria are increasingly resistant to antibiotics, and existing drugs work poorly against chronic infections like those that occur in wounds, on medical devices and in the lungs of people with cystic fibrosis. For these reasons, a great deal of research is focused on finding new antibiotic compounds.

In this study, researchers took a different approach. Rather than trying to find agents that best killed bacteria in test tubes, they sought to intensify the stress imposed on microbes by one of the body's own defense mechanisms.

"The competition for iron is critical in the struggle between bacteria and host," explained the study's senior author, Pradeep Singh, associate professor of medicine and microbiology at the UW. "The body has potent defense mechanisms to keep iron away from infecting organisms, and invaders must steal some if they are to survive."

Iron is critical for the growth of bacteria and for their ability to form biofilms, slime-encased colonies of microbes that cause many chronic infections. "Because iron is so important in infection, we thought infecting bacteria might be vulnerable to interventions that target iron," explained Yukihiro Kaneko, senior fellow in microbiology at the UW and the study's lead author.

To accomplish this, the researchers used gallium, a metal very similar to iron.

"Gallium acts as a Trojan horse to iron-seeking bacteria," said Singh. "Because gallium looks like iron, invading bacteria are tricked, in a way, into taking it up. Unfortunately for the bacteria, gallium can't function like iron once it's inside bacterial cells."

Source

Other approaches include locating bacterial signaling proteins that are vital to the normal development of bacterial resistance--and paralysing them. Weakening the bacteria in this way should make otherwise virulent organisms more vulnerable to the body's immune attack, and conventional antibiotics. As one researcher put it: "Evolution is not an unstoppable force," says [Floyd] Romesberg. "There is a biochemistry underlying it and it is subject to intervention."

Other innovative approaches may yet free medical practice from the treadmill of bacterial resistance. Using viruses to fight bacteria would be one way to get evolution to work for us.

Then again, we might get lucky from time to time. Common drugs used to fight fungal infections are being looked at as potentially powerful weapons against multiple drug resistant TB--a modern scourge. Finding drugs that have already passed through the grueling testing process, which are effective against one of the worst infections known, would be fortuitous.