Cation Catcher

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Science  05 Dec 2008:
Vol. 322, Issue 5907, pp. 1437-1439
DOI: 10.1126/science.322.5907.1437d

The lungs of cystic fibrosis (CF) sufferers always become colonized with antibiotic-resistant bacteria and are traumatized by inflammatory responses as they become blocked with mucus, alginate, and DNA. The DNA may originate from bacteriophage- or host-mediated disruption of bacteria but may also come from the host as infiltrated immune cells lyse. Mulcahy et al. noted that DNA is highly anionic and went on to show that, whatever its source, it can act as a chelator of Mg2+ and Ca2+. At high concentrations, presumably in areas adjacent to the epithelium of the lung, DNA soaks up cations to cause gross membrane disruption and thus has a strong antimicrobial effect. It's not all good news, though, as physicochemical gradients form deeper within the clots of mucus and the bacterial biofilm within the airways. At lower concentrations, the DNA soaks up just enough cations to trigger signalling cascades that culminate in the addition of aminoarabinose to the surface lipopolysaccharide molecules of the major pathogen in CF, Pseudomonas aeruginosa. This change renders the bacterium resistant to small defensive peptide molecules produced by the host as well as to aminoglycoside antibiotics. — CA

PLoS Pathogens 4, e1000213 (2008).

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