AUTHOR=Lewenza Shawn 

TITLE=Extracellular DNA-induced antimicrobial peptide resistance mechanisms in Pseudomonas aeruginosa

JOURNAL=Frontiers in Microbiology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2013.00021

DOI=10.3389/fmicb.2013.00021

ISSN=1664-302X

ABSTRACT=<p>Extracellular DNA (eDNA) is in the environment, bodily fluids, in the matrix of biofilms, and accumulates at infection sites. eDNA can function as a nutrient source, a universal biofilm matrix component, and an innate immune effector in eDNA 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. eDNA binds metal cations and thus activates the Mg<sup>2+</sup>-responsive PhoPQ and PmrAB two-component systems. In <italic>Pseudomonas aeruginosa</italic> and many other Gram-negative bacteria, the PhoPQ/PmrAB systems control various genes required for virulence and resisting killing by antimicrobial peptides (APs), including the <italic>pmr</italic> genes (<italic>PA3552</italic>–<italic>PA3559</italic>) that are responsible for the addition of aminoarabinose to lipid A. The <italic>PA4773</italic>–<italic>PA4775</italic> 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 AP treatment. Both modifications mask the negative surface charges and limit membrane damage by APs. DNA-enriched biofilms or planktonic cultures have increased antibiotic resistance phenotypes to APs and aminoglycosides. These dual antibiotic resistance and immune evasion strategies may be expressed in DNA-rich environments and contribute to long-term survival.</p>