Culturing the Unculturable

Culturing bacteria is't always this easy.

Culturing bacteria is’t always this easy.

It is estimated that all the bacterial species so far described represent only a tiny fraction of the total. The rest remain unknown to science because they are “unculturable” in standard (or known) laboratory media. Given that many antibiotics were first isolated from environmental bacteria, it seems likely that these as yet unknown organisms could also be a rich source of potential new drug candidates. The desperate need for new strategies to combat multi-drug resistant infections gives impetus to studies investigating how we can culture some of these “unculturable” bacteria and uncover their potential as a source of much-needed new treatments.  Continue reading

Mining Genomes for Antimicrobials

searching for new antibioticsWhile looking through some “Top Ten” lists of the various science stories and discoveries of 2014, I came across a paper, published in Cell in September, describing a new approach to the search for antimicrobials. The paper’s authors screened the vast amount of genomic data from the human microbiome project against known sequences to find genes with homology to existing small molecule drug candidates.

The authors reasoned that any genes that were common across many species would be more likely to affect conserved microbe:host or microbe:microbe interactions. Having identified a large group of these gene clusters, they then homed in on a subset that was commonly found in the microbiome of healthy individuals. As a proof-of-concept, they then identified and characterized a thiopeptide molecule produced by the bacterium Lactobacillus gasseri  and showed that it had the expected antimicrobial activity. The Cell paper was the first report of the characterization of any small molecule drug candidate isolated from the human microbiome. Continue reading

Hope for Treatment of Carbapenem-Resistant Bacteria

Structure of the antibiotic meropenem

Structure of the antibiotic meropenem

Last month brought some hopeful news on the subject of antibiotic resistance. A paper published in Nature on June 26 described the isolation of a fungal compound that restored the antibiotic sensitivity of carbapenem-resistant enterobacteria. An editorial accompanying the paper took encouragement from the article–considering it a sign that the well of potential sources of new antimicrobial agents, and agents that inhibit resistance mechanisms, is not yet dry:

But the reservoir of natural products with the potential to act as antibacterial drugs has not yet been exhausted. In contrast to general thinking by drug companies, screening for such products may well still have a bright future” Nature News and Views: “Antibiotic resistance: To the rescue of old drugs” Meziane-Cherif & Courvalin, Nature 510, 477–478.

The emergence of bacteria that are resistant to antibiotics has been an object lesson in the relentlessness of natural selection; the moment a new antibiotic is developed and introduced, the countdown to the emergence of resistance begins. The race to keep the one step ahead of emerging resistance mechanisms has been going on since antibiotics were first introduced.

The history of the development of penicillin and related antibiotics is both an illustration of the ingenuity of scientists and of the never-ending nature of this battle with emerging resistance. The Nature paper is the latest installment in that story. Continue reading

Just a Spoonful of Honey is Medicine Enough

As we face more challenges when treating and healing humans, revisiting therapies that fell out of favor has become more common. For example, people with open wounds that are not healing receive judicious applications of maggots to remove necrotic tissue and promote healing. Leeches are used for patients after surgery to prevent blood clotting in swollen tissues and encourage healing. However, not all therapies involve direct application of squirmy creatures to skin; in fact, honey is one item people are willing to have in their homes. Honey has been used as a sweetener for food, for soothing sore throats and coughs and, more recently, for treating wounds unresponsive to traditional antibiotic therapy. In a recent PLoS ONE paper, the authors assessed the properties that are associated with honey’s antimicrobial activity against pathogenic and food-spoiling bacteria. Continue reading