PLoS ONE Prokaryotic Genome Collection

PLoS ONE unveiled their new Prokaryotic Genome Collection today, along with an editorial by Section Editor Niyaz Ahmed. Well done, Niyaz! Everyone else: send us your best genome papers!

Our new PLoS ONE paper is out!

Our new paper about detection and inhibition of vaginolysin, the human-specific toxin from Gardnerella vaginalis, came out on line today! [Link] Please check it out and rate/comment if you can!

E. coli and your receptors

Ok. This is cool. I took a break from grant-writing to read this paper, and I’m glad that I did. Starting with an in silico screen, Cirl et al. showed that some pathogenic bacteria (they focused on uropathogenic E. coli) secrete proteins that are homologues of a domain of the mammalian toll-like receptors (TLR). TLR are the sentinel molecules of the innate immune system, detecting conserved pieces of pathogens (peptidoglycan, lipopolysaccharide, or good-old bacterial DNA) and initiating immune responses. They are present on all kinds of cells, including the epithelial cells that line the urinary tract. The E. coli proteins that this group found bind to the TIR domain, the part of TLR that are responsible for transducing signals, and interrupt the signaling cascade, effectively silencing the alarm. This blunts the immune response and, presumably, protects the bacteria from attack. The paper is a great piece of work, telling a coherent story and taking the idea from the initial screen to a mechanistic investigation that has real clinical implications. Well done!

Link to article. (Sadly, not open access.)


Cirl, C., Wieser, A., Yadav, M., Duerr, S., Schubert, S., Fischer, H., Stappert, D., Wantia, N., Rodriguez, N., Wagner, H., Svanborg, C., Miethke, T. (2008). Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain–containing proteins. Nature Medicine DOI: 10.1038/nm1734

Screening for new antibiotic resistance genes

A recent article in PLoS ONE takes a broad look at antibiotic resistance in Pseudomonas aeruginosa, an environmental organism and a cause of opportunistic infections. Pseudomonas infections are particularly difficult to treat, as it is frequently resistant to numerous classes of antibiotics. Children who are predisposed to chronic colonization or infection with Pseudomonas, such as those with cystic fibrosis, may eventually harbor bacteria that are resistant to all available antibiotics. Fajardo et al. (citation below) screened two transposon libraries of P. aeruginosa looking for genes that either increased or decreased susceptibility to a panel of antibiotics. Their results are of interest, as many of their hits (genes associated with a change in susceptibility) were in classes of genes not previously linked to resistance. A weakness of the study is that they do not go on to make defined mutations in these genes or to complement the phenotype by expressing the mutated gene on a plasmid, but it is an interesting screen that has the potential to provide targets for future antimicrobial development.

Here is the PubMed link so that you can reach the PubMed Central version of the article if the PLoS ONE site continues to be slow.

Fajardo, A., Martínez-Martín, N., Mercadillo, M., Galán, J.C., Ghysels, B., Matthijs, S., Cornelis, P., Wiehlmann, L., Tümmler, B., Baquero, F., Martínez, J.L., Falagas, M. (2008). The Neglected Intrinsic Resistome of Bacterial Pathogens. PLoS ONE, 3(2), e1619. DOI: 10.1371/journal.pone.0001619

Avery and the pneumococcus

I gave a lecture on Streptococcus pneumoniae (pneumococcus) in our global antimicrobial resistance course today. Despite more than a hundred years of work, the pneumococcus remains a major cause of morbidity and mortality worldwide. We have vaccines, we have effective antibiotics (fewer and fewer…), yet pneumococcal infection still kills about a million kids every year.

Here’s something that I do when I want to feel small: I look back at the papers that Oswald Avery published on the topic of the pneumococcus between 1915 and 1946 in the Journal of Experimental Medicine. (Thanks, JEM, for opening up your archive back to the very first issue!). Not only is the paper defining DNA as the transforming substance in there, but nearly everything that we understand about the pneumococcus was done or predicted by Avery. The carrier state, capsular polysaccharide (and the fact that one can diagnose pneumococcal infection by detecting it in the urine), autolysis, hydrogen peroxide production, discovery of C-reactive protein, and how to make a conjugate vaccine: it’s all there. Our best diagnostics and vaccines are still offshoots of his work.

As with any great scientist, he did not work alone, and many others have contributed to advancing the field, but I remain in awe of Avery.




Dochez, A.R., Avery, O.T. (1915). THE OCCURRENCE OF CARRIERS OF DISEASE-PRODUCING TYPES OF PNEUMOCOCCUS . Journal of Experimental Medicine, 22(1), 105-113.