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.