Extracellular DNA-induced antimicrobial peptide resistance mechanisms in Pseudomonas aeruginosa.

• Main Author: Shawn eLewenza
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2013-02-01
• Series: Frontiers in Microbiology
• Subjects: Immune Evasion; Biofilm; antibiotic resistance; antimicrobial peptides; extracellular DNA; PhoPQ
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fmicb.2013.00021/full

Extracellular DNA (eDNA) is in the environment, bodily fluids, in the matrix of biofilms, and accumulates at infection sites. Extracellular DNA can function as a nutrient source, a universal biofilm matrix component and an innate immune effector in extracellular DNA traps. In biofilms, eDNA is required for attachment, aggregation and stabilization of microcolonies. We have recently shown that eDNA can sequester divalent metal cations, which has interesting implications on antibiotic resistance. Extracellular DNA binds metal cations and thus activates the Mg2+-responsive PhoPQ and PmrAB two-component systems. In Pseudomonas aeruginosa and many other Gram-negative bacteria, the PhoPQ/PmrAB systems control various genes required for virulence and resisting killing by antimicrobial peptides, including the pmr genes (PA3552-PA3559) that are responsible for the addition of aminoarabinose to lipid A. The PA4773-PA4775 genes are a second DNA-induced cluster and are required for the production of spermidine on the outer surface, which protects the outer membrane from antimicrobial peptide treatment. Both modifications mask the negative surface charges and limit membrane damage by antimicrobial peptides. DNA-enriched biofilms or planktonic cultures have increased antibiotic resistance phenotypes to antimicrobial peptides and aminoglycosides. These dual antibiotic resistance and immune evasion strategies may be expressed in DNA-rich environments and contribute to long-term survival.