Endolysin-A new tool to overwhelm Super Bugs

The so called super bugs which have emerged during the last few years which are resistant to most known antibiotics may imperil the lives of millions of people infected by them if suitable alternative therapy is not developed fast. Though many scientists are working to evolve satisfactory antidotes to them success has been far and few. One of the reasons is lack of investment in developing new classes of antibiotics that can destroy them. Reckless use of antibiotics for even those afflictions not caused by pathogenic bacteria and for non-medical purpose like incorporating in animal feed for fattening the animals or lacing the growing medium by aqua culture industry have greatly contributed to emergence of super bugs not responsive to normal antibiotics. It has been shown clearly that many bacteria can create biofilms around them which are unimpregnable and therefore inaccessible to the antibiotic molecule making it ineffective. If this film can be breached, the bacterial cells are highly vulnerable to destruction. Such an approach seems to have succeeded with a group of scientists in the Netherlands coming out with a biological agent (endolysins) that can be effective in exploiting the chink in the armor of these pathogens offering alternative therapy for killing drug resistant organisms. Here is a take on this new exciting development.

"In a breakthrough, scientists have developed the first effective alternative to antibiotics that may aid the fight against drug-resistant infections.  In a small patient trial, the drug was shown to be effective at eradicating the superbug Methicillin-resistant Staphylococcus aureus (MRSA). Researchers said it is unlikely that the infection could develop resistance against the new treatment, which is already available as a cream for skin infections. They hope to develop a pill or an injectable version of the drug within five years. The treatment marks "a new era in the fight against antibiotic-resistant bacteria," according to Mark Offerhaus, chief executive of the biotechnology company Micreos, which is behind the advance. The treatment attacks infections in an entirely different way from conventional drugs and, unlike them, exclusively targets the Staphylococcus bacteria responsible for MRSA, and leaves other microbes unaffected. The approach is inspired by naturally occurring viruses that attack bacteria using enzymes called endolysins. It uses a 'designer' endolysin, Staphefekt, which the scientists engineered to latch on to the surface of bacteria cells and tear them apart, 'The Times' reported. "Endolysins exist in nature, but we've made a modified version that combines the bit that is best at binding to the bacteria with another bit that is best at killing it," said Bjorn Herpers, a clinical microbiologist, who tested the drug at the Public Health Laboratory in Kennemerland, the Netherlands. Conventional antibiotics need to reach the inside of the cell to work, and part of the reason they are becoming less effective is that certain strains of bacteria, such as MRSA, have evolved impenetrable membranes. By contrast, endolysins target basic building blocks on the outside of bacterial cells that are unlikely to change as infections genetically mutate over time. Scientists believe that the results could mark the first of a wave of endolysin-based therapies for infections that conventional drugs are no longer able to treat. About 80 per cent of gonorrhoea infections are resistant to frontline drugs, and multidrug-resistant salmonella, tuberculosis and E coli are regarded as significant threats. Naturally occurring endolysins can attack all of these diseases, and the challenge is to create stable versions that can be packaged as drugs, researchers said." 

It is encouraging to note that new endolysins are being evolved to attack and kill the organisms concerned containing both the cell membrane busting molecule and the killing molecule. Formulations like skin creams, tablets and injections may be in the offing soon and the specter of epidemics caused by these hitherto indestructible vectors may not be that daunting if these developments are taken to their logical conclusion. Interestingly endolysins do not seem to be affecting normal bacteria unlike antibiotics which when taken orally cause considerable havoc in the intestine harming many beneficial bacteria, part of human microbiome, considered critical to the well being of man. Those afflicted by deadly diseases like gonorrhoea, salmonella, tuberculosis, virulent E.coli, etc can heave a sigh of relief if the new therapy is brought to main the stream medical practices.

V.H.POTTY
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NEW "TB" DANGERS-INDIA AND CHINA IN THE SAME BOAT?

Tuberculosis more commonly known as TB or MTB  is a scourge affecting millions of people in poor countries, caused mainly by the bacterium, Mycobacterium tuberculi. Though it is estimated that almost one third of the world population carry this infection with those in poor countries accounting for 80% of the cases but only about 13 million people are chronically affected by TB and the death toll due to this disease is estimated to be about 1.5 million per year. The bacteria affect the lungs and its manifestation is through coughing with bloody sputum, fever, night sweats and weight loss during the active progress of the disease. One of out of every latent carriers of TB progress to chronic stage. TB spreads through air and those who are active carriers can infect others through sneezing, coughing and saliva. As the bacterium has strong outer cell wall, drugs often prove to be ineffective in treating this disease. Though during initial stages single antibiotic may work, multi drug treatment is the only option at later stages. drugs like Rifampicin, Isoniazid, Pyrazinamide, Ethambutol are the choices administered singly or in combinations. Recent reports that TB variants resistant to all known drugs are emerging in China and India are indeed alarming. Here are two such reports which illustrate the dangers posed by such drug resistant TB in these countries.    

Out of the million Chinese who develop TB every year, researchers say at least 110,000 get a form that's resistant to the mainstay drugs isoniazid and rifampin. Patients with such multidrug-resistant or MDR tuberculosis have to be treated for up to two years with expensive second-line drugs that are toxic and less effective. Worse yet, the new survey shows that at least 8,200 Chinese are coming down with extensively resistant or XDR-TB. That means it's also resistant to at least two of the second-line drugs — and thus may be incurable in many cases. And still worse, most of these resistant cases are being passed from patient to patient. So drug-resistant forms of TB are circulating in the community, they're not just being created one patient at a time when an individual doesn't get a full course of the right drugs (although that's happening too). "The results of this nationwide survey in China confirm that the country has a serious epidemic of drug-resistant tuberculosis," write study authors, who mostly work at the Chinese Center for Disease Control and Prevention, a government agency. Writing in the New England Journal of Medicine, the researchers report that a third of new TB cases and half of patients with previously treated TB have drug-resistant forms. "China has the highest annual number of MDR tuberculosis in the world — a quarter of the cases worldwide," the Chinese experts note in a forthright statement that bears no trace of muting the problem for the sake of national pride.

Tuberculosis specialists in India have diagnosed infections in a dozen patients in Mumbai that are unfazed by the three first-choice TB drugs and all nine second-line drugs. The doctors are calling them "totally drug-resistant TB," and the infections are essentially incurable with all available medicines. It's a sobering development. Infectious disease specialists say there will surely be more such cases in India and other countries where cases of TB that resist some but not all drugs are being inadequately treated. Poor care is fueling the development of the super bugs. "The vast majority of these unfortunate patients seek care from private physicians in a desperate attempt to find a cure for their tuberculosis," the Indian specialists write in Clinical Infectious Diseases. "The majority of these prescriptions were inappropriate and would only have served to further amplify resistance." The team did a study that showed only five of 106 private practitioners "wrote the correct prescription for treating TB," Dr. Zarir F Udwadia, one of the study authors, told Daily News and Analysis, an Indian publication. "The other TB challenge is diagnosis, especially of resistant strains, and here again the news is not good," writes infectious disease blogger Maryn McKenna. "The World Health Organization said last spring that only two-thirds of countries with resistant TB epidemics have the lab capacity to detect the resistant strains." Johns Hopkins TB researcher Dr. Richard Chaisson tells Shots that "total resistance is a new phenomenon that is entirely predictable." It's predictable, he says, because hundreds of thousands of people in India have what's called multidrug-resistant TB, or MDR-TB. And a growing number have "extensively resistant TB," or XDR-TB. And very, very few of them are getting the expensive, hard-to-take drugs that might cure their infections. "If you don't provide supervised second-line drugs, this is what you're going to see," agrees Dr. Carol Dukes Hamilton of Duke University. "People go to practitioners who aren't TB experts. They don't give the right doses or make sure people take them." Still, the development of these cases of totally resistant TB doesn't necessarily mean epidemics will sweep through India, or anywhere else, right away. For one thing, there's no evidence so far that patients with these defiant TB strains are transmitting them to others. Most likely, Hamilton says, these patients didn't catch the maximally resistant TB strain from someone else. Rather each patient probably incubated his or her own totally resistant strain after being inadequately treated. That allows the TB bacterium to develop resistance to one drug after another. Technically, the Indian cases might not really be totally resistant. The Mumbai specialists didn't try some so-called third-line experimental drugs that U.S. doctors might use in such cases. At least one of the Mumbai patients did have surgery to remove diseased lung tissue, but she died anyway. But practically speaking, such treatments aren't usually available in India or many other places where totally drug-resistant cases may arise. The problem of evolving TB drug resistance has been brewing for years. In the early 1990s, multidrug-resistant TB began spreading in New York City, abetted by homelessness, prison outbreaks and HIV. Aggressive identification and treatment of these cases, including the direct observation of patients taking their pills, snuffed out that epidemic. In 2005, extensively drug-resistant TB — strains untreatable with the three first-line drugs and several second-choice medications — cropped up in the South African province of Kwazulu-Natal, again abetted by HIV, which devastates immune defenses. Chaisson says South Africa has since mounted an effective program of treatment with the few drugs that work against XDR-TB. "But they have more patients than they have treatment slots," he says. Two Italian women with HIV were the first recognized cases of "totally drug-resistant TB" back in 2003. Another 15 patients with totally resistant infections were discovered in 2009 in Iran. So nobody expects the new Mumbai cases will be the end of this troubling new phenomenon.

BCG vaccination during early childhood was a standard procedure to protect children from TB infection but there is no unanimity regarding the effectiveness of the this preventive measure. Its performance has been erratic besides losing its potency after the age of 10 years. Another potent TB causing bacterium T. bovis has become almost extinct after the advent of milk pasteurization technology that is able to eliminate this species from milk. Other lesser known species like M. africanum, M.canetti and M.microti are not so virulent and wide spread, deserving much attention. How this bacterium has been able to evolve into multi drug resistant version is a matter of speculation. Many TB treatment specialists opine that Multi Drug resistant Tuberculosis develops because of sub-optimal treatment meted out by local physicians helping the bacterium to evolve into resistant versions over a period of time. Both China and India need to gear up their TB monitoring and treatment infrastructure to stop the spread of this scourge on its track immediately.  

V.H.POTTY
http://vhpotty.blogspot.com/
http://foodtechupdates.blogspot.com