Biomedicine Select

Antibiotic-resistant bacteria are a serious threat to human health. A recent study by D’Costa et al. reveals that multidrug-resistant microbes are far more prevalent than previously imagined. This group examined soil microbes for antibiotic resistance. First, they isolated sporeforming bacteria from different environments and then selected the actinomycetes (confirmed by sequencing 16S ribosomal DNA) for further study. They focused on 480 actinomycetes of the genus Streptomyces, because more than half of all antibiotics are derived from this species. Hence, members of this species are likely to encode resistance elements for the antibiotics they produce as a means of self-protection. These 480 strains were individually tested for their ability to grow in the presence of 21 antibiotics including natural (such as erythromycin), semisynthetic (such as cephalexin), and synthetic (ciprofloxacin) antibiotics. Strikingly, every strain was found to be resistant to seven or eight antibiotics, even newer antibiotics. In some cases, resistance was due to the production of inactivating enzymes that metabolized the drug. One such drug was rifampicin, a derivative of a natural product, which is used routinely to treat mycobacterial infections (which cause diseases such as tuberculosis). Forty percent of the bacteria resistant to rifampicin could inactivate the antibiotic. Interestingly, in a clinical setting, resistance to rifampicin is caused by mutations in the bacterial target of this drug, the b subunit of RNA polymerase. Other mechanisms of resistance include glycosylation (which inactivates telithromycin) and natural mutations in the gene encoding the cellular target (DNA gyrase in the case of ciprofloxacin). As this study is limited to Streptomyces and used high concentrations of antibiotics, the full spectrum of antibiotic resistance that may reside in other soil bacteria remains unknown. Another crucial question is whether this reservoir of antibiotic resistance is a source of the genetic elements that confer resistance to pathogens. V.M. D’Costa et al. (2006). Science 311(5759):374–7.