Links of note/Science

Bacterial genomics: A new source of antimicrobial targets : Nature Reviews Microbiology

Posted on by charlie

“Bacterial clone-based genome sequencing frequently results in gaps, which harbour hypothetical genes of unknown function. Sorek and colleagues show that these gaps contain a vast array of genes encoding proteins that are toxic to the sequencing host (Escherichia coli), including previously uncharacterized restriction enzymes, toxin–antitoxin systems and non-coding RNAs.”

Of course, to me, this is very clever, having never thought about this. Yes, we always knew that some sequences were unclonable because of incompatibility with the cloning vector. But the cleverness is to actually look for those gaps as potential anti micribials. That’s one of those amazing “Duh”s that sometimes happen when things are right under our nose.

Only sucky thing is that the article is CLOSED ACCESS. Fail.

via Access : Bacterial genomics: A new source of antimicrobial targets : Nature Reviews Microbiology (subscription required).

Links of note/Science/Strategy

A Method for Generation Phage Cocktail with Great Therapeutic Potential – PLoS ONE

Posted on by charlie

“Bacteriophage could be an alternative to conventional antibiotic therapy against multidrug-resistant bacteria. However, the emergence of resistant variants after phage treatment limited its therapeutic application. Our data showed that the phage cocktail was more effective in reducing bacterial mutation frequency and in the rescue of murine bacteremia than monophage suggesting that phage cocktail established by SBS method has great therapeutic potential for multidrug-resistant bacteria infection.”

Biologic warfare at the bacterial level. In some developed countries antibiotic misuse has caused the rapid development of antibiotic-resistant bacteria. Bacteriophage therapy has therefore taken a more important role. Except, it has its issues. In this paper, they work to avoid phage resistance with a multi-phage approach.

Read this article…

Links of note/Science/The Narrative

Macro and Micro Diversity of Clostridium difficile Isolates from Diverse Sources and Geographical Locations – PLoS ONE

Posted on by charlie

“Clostridium difficile has emerged rapidly as the leading cause of antibiotic-associated diarrheal disease, with the temporal and geographical appearance of dominant PCR ribotypes. We have undertaken a breadth genotyping study using multilocus sequence typing (MLST) analysis of 385 C. difficile strains from diverse sources by host (human, animal and food), geographical locations (North America, Europe and Australia) and PCR ribotypes. Results identified 18 novel sequence types (STs) and 3 new allele sequences and confirmed the presence of five distinct clonal lineages generally associated with outbreaks of C. difficile infection in humans.”

A broad survey to understand the nature of this pesky and increasingly common pathogen.

Read this article…

Innovation/Links of note/Science/Strategy

Broad Institute Gets $32.5 Million to Map Cell Circuits – ScienceInsider

Posted on by charlie

“The Broad isn’t alone: Mount Sinai School of Medicine in New York City, the Allen Institute for Brain Science in Seattle, the Salk Institute in San Diego, and University of California, San Diego, are also launching major efforts to study cell circuitry, says UCSD computational biologist Trey Ideker. He suggests that eventually these groups should form a “big, coordinated science project” so that they can divide up the task of mapping circuits in different cell types. “This is a very big goal and in a sense the logical successor to the Human Genome Project,” Ideker says.”

Mapping cellular circuits – very interesting.

Read this article…

Links of note/Science/Strategy

Two-Drug Antimicrobial Chemotherapy: A Mathematical Model and Experiments with Mycobacterium marinum – PLoS Pathogens

Posted on by charlie

This paper is trying to measure and model the effectiveness of multi-drug antimicrobial chemotherapy.

Antibiotics are notorious for losing effectiveness as the target microbe gains resistance to that single antibiotic. Being able to treat microorganism with multiple drugs is sometimes the only way to manage the disease – as in HIV or TB.

But to be able to create better multi-drug cocktails, we’ll need to better model the contributions of each component.

This paper seeks to show how to measure and prove the effectiveness of the component sin a two-drug system. But I am wondering how we’ll do the same for more than two drugs (HIV anti-viral therapy has at least three components).

Read this article…

Links of note/Science/Strategy/The Narrative

Patterns of Gene Flow Define Species of Thermophilic Archaea: PLoS Biology

Posted on by charlie

“Patterns of homologous gene flow among genomes of 12 strains from a single hot spring in Kamchatka, Russia, demonstrate higher levels of gene flow within than between two persistent, coexisting groups, demonstrating that these microorganisms fit the biological species concept. Furthermore, rates of gene flow between two species are decreasing over time in a manner consistent with incipient speciation.”

This is a really cool paper analyzing speciation in action. It shows how microbes slowly become less likely to swap genetic information as they differentiate. A key concept, too, is that each species has its own genetic island.

Great stuff.

Read this article…

Links of note/Science/The Narrative

Influence of Milk-Feeding Type and Genetic Risk of Developing Coeliac Disease on Intestinal Microbiota of Infants: The PROFICEL Study

Posted on by charlie

“This study demonstrates that the milk-feeding type and the HLA-DQ genotype differently influence the bacterial colonization pattern of the newborn intestine during the first 4 months of life and, therefore, could also influence the risk of developing CD in later life. Breast-feeding reduced the genotype-related differences in microbiota composition, which could partly explain the protective role attributed to breast milk in this disorder.”

Interesting study doing two things: 1) showing an effect of genotype on bacterial populations in the gut – and that they are different for those at risk for celiac disease; and, 2) showing a difference between the bacterial populations of breast-fed and formula-fed children, and a possible microbial reason why breast-feeding protects against celiac disease.

Very cool. And scary how it makes such good sense.

Read this article in PLoS ONE.

Links of note/Science/Strategy/The Narrative

Crowd-Sourcing Drug Discovery

Posted on by charlie

“The first challenge that OSDD’s cyber-community assigned itself was to glean more information from the M. tuberculosis genome. It was sequenced in 1998, but researchers had clues to the functions of only a quarter of its 4000 genes. In December 2009, OSDD set out to reannotate all possible genes. Some 500 volunteers got the job done in a mere 4 months. Now OSDD is trying to exploit these data. “The more people you put to work on the problem, the more chances you will have to identify the set of compounds that will likely make it through compound optimization, animal models, preclinical, and, eventually, clinical trials. If you increase your success chances, then your overall costs decrease,” says Marc Marti-Renom of the National Center for Genomic Analysis in Barcelona, Spain.”

FoldIt, GalaxyZoo, now this. Is the next phase of computing networked human computing?

Read this article…

Links of note/Science/Strategy/The Narrative

Biodiversity of Indigenous Saccharomyces Populations from Old Wineries of South-Eastern Sicily: Preservation and Economic Potential

Posted on by charlie

“We report on the remarkable degree of biodiversity in the wine yeast populations naturally present in a small area of Sicily where traditional (non-industrial) winery practices are still in place. Out of more than 900 yeast isolates recovered from late spontaneous fermentations, we detected at least 209 strains. Given that the characteristics of the wines produced were found to be industrially appealing, the study demonstrated the economic potential of preserving the patrimony of Sicilian yeast biodiversity and highlighted the importance of maintaining traditional wine making practices.”

This is a great paper – studying the biodiversity of yeast obtained from traditional wineries; analyzing their genetic and metabolic qualities; and even using a few to make wines.

How fun. How inspiring.

Read this article in PLoS ONE

UPDATE 15mar12: Science wrote a nice review on this article. Ironic though that a publication with closed access articles is writing about an open access article.