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Archive for the ‘Drugs/Medicines’ Category

The sting in the tail of antibiotic use

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4535625164_f4090e1a8e_zResearchBlogging.orgRecently, I found a paper published in mBIO that describes how antibiotic use in farming is involved in the spread of resistance genes. In this case the work focuses on the humble honeybee (Apis mellifera). Since the 1950s, beekeepers in the USA have been using the antibiotic oxytetracycline – a ‘broad-spectrum’ antibiotic that kills most species of bacteria – to prevent infections that can cause ‘foul brood’, a disease that kills bee larvae.  As you can imagine, using a single antibiotic for more than 50 years has led to some selective pressure. In this work, researchers from Yale University were investigating the prevalence of disease resistance in bee gut bacteria.

This might seem like a strange place to look, but it actually has its advantages. Unlike the supremely complex ecosystem of the human gut microbiome, the bee’s is pretty simple, with eight species making up over 95% of the gut bacteria in adult worker bees. The small number of species and the knowledge of how hives have been treated allowed the researchers to monitor the impact of decades of antibiotic use.

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Written by Benjamin Thompson

22/01/2013 at 10:00 am

Drug resistance and persistence in Mycobacterium tuberculosis

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ResearchBlogging.orgAs we’ve discussed before, Mycobacterium tuberculosis is the major cause of tuberculosis, a disease that has plagued humans for millennia. The oldest recorded case of TB is in a 500 000-year-old fossil of Homo erectus. Despite the best efforts of modern medicine, we have so far failed in our fight against this disease, which kills up to two million people every year.

The problem is that M. tuberculosis infections are both hard to detect and hard to treat. Mycobacteria have a waxy coating of fats called mycolic acids that make them naturally resistant to many antibiotics and helps them hide inside human immune cells. Because the immune system can’t attack itself, this is a pretty ingenious hiding place. It typically takes six months of multidrug therapy to cure an active TB infection and nine months to kill a latent infection (that is, the TB cells that are hiding). Some of the cells that are hiding are known as ‘persisters’, and it’s these cells that take longer to kill in a latent infection.

In a recent study, scientists developed a new way to study persister cells in the lab. They found that in a large collection (or population) of TB cells, a small number form a distinct subgroup of persisters. Weirdly, despite all the cells being genetically identical, the persisters are more resistant to antibiotics than all the other normal TB cells.

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Written by microbelog

21/08/2012 at 10:00 am

Guest post: New ammunition in the fight against infection

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False coloured light micrograph of MRSA colonies.

ResearchBlogging.orgMost of us have at some point in our life received a course of antibiotics to treat a bacterial infection. However,  treatment options are becoming limited for many infections, as some bacteria have developed resistance to multiple antibiotics, such as the ‘superbug’ methicillin-resistant Staphylococcus aureus (MRSA), or the recently emerged totally drug-resistant (TDR) TB.

With drug resistance making bacterial infections increasingly difficult to treat, the search for new antibiotics has become more urgent than ever. This makes the discovery of acyldepsipeptides, a new class of antibiotics, very welcome indeed. Acyldepsipeptides are effective against some of the most prominent human-disease causing bacteria, including MRSA, and have attracted a great deal of attention as potential new drugs. They are distinct from all of the antibiotics currently used in the clinic as they have a novel target in the bacterial cell, as described in a paper published in PNAS.

Most antibiotics target one of four essential bacterial processes: cell wall biosynthesis; nucleic acid biosynthesis; protein synthesis; or folic acid biosynthesis (required for making DNA, RNA and proteins). Acyldepsipeptides work differently, blocking cell division – vital for bacterial survival.

Normally, bacteria multiply by dividing in two, producing identical copies of themselves. Acyldepsipeptides stop this process by binding to a bacterial enzyme called ClpP:  a protease that destroys unwanted or damaged proteins. Acyldepsipeptides change the action of ClpP so that it specifically targets and destroys FtsZ, a protein that marks the site at which bacterial cell division should occur.

Destruction of FtsZ leads to the formation of long, filamentous bacteria that continue to grow but cannot divide. Crucially, this means that the bacteria cannot multiply and spread to cause infection.

The discovery of a new class of antibiotics, with a new cellular target, provides us not only with potentially lifesaving drugs, but also a glimmer of hope of unearthing yet more novel antibiotics and targets for the treatment of multi-drug resistant bacteria.

Claire Bushell

Claire is an undergraduate student at the University of East Anglia

Sass, P., Josten, M., Famulla, K., Schiffer, G., Sahl, H., Hamoen, L., & Brotz-Oesterhelt, H. (2011). Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ Proceedings of the National Academy of Sciences, 108 (42), 17474-17479 DOI: 10.1073/pnas.1110385108

Image Credit: Wellcome Images on Flickr

Written by microbelog

02/05/2012 at 9:57 am

Mixing your drugs kills superbugs!

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Pseudomonas aeruginosa

We hear a lot in the news about multidrug-resistant (MDR) bacteria but not very much about the efforts made to tackle these so-called ‘superbugs’.

At the recent ‘Antibiotics 2011’ meeting hosted by the Royal Society of Chemistry, I heard some interesting talks from senior scientists working for the pharmaceutical giants GlaxoSmithKline and Bayer.

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Written by microbelog

11/08/2011 at 10:35 am