title: A Mig-14-like protein (PA5003) affects antimicrobial peptide recognition in Pseudomonas aeruginosa.
abstract: The evolution of antibiotic resistance in pathogenic bacteria is a growing global health problem which is gradually making the treatment of infectious diseases less efficient. Antimicrobial peptides are small charged molecules found in organisms from the complete phylogenetic spectrum. The peptides are attractive candidates for novel drug development due to their activity against bacteria that are resistant to conventional antibiotics, and reports of peptide resistance are rare in the clinical setting. Paradoxically, many clinically relevant bacteria have mechanisms that can recognize and respond to the presence of cationic antimicrobial peptides (CAMPs) in the environment by changing the properties of the microbial surface thereby increasing the tolerance of the microbes towards the peptides. In Pseudomonas aeruginosa an essential component of this inducible tolerance mechanism is the lipopolysaccharide modification operon arnBCADTEF-PA3559 which encodes enzymes required for LPS alterations leading to increased antimicrobial peptide tolerance. The expression of the operon is induced by the presence of CAMPs in the environment but the molecular mechanisms underlying the cellular recognition of the peptides are poorly elucidated. In this work, we investigate the factors influencing arnB expression by transposon mutagenesis and arnB promoter green fluorescent protein reporters. We have identified a novel gene encoding a Mig-14-like protein that is required for recognition of the CAMPs colistin and Novispirin G10 by P. aeruginosa. Moreover, we show that this gene is also required for the formation of CAMP-tolerant subpopulations in P. aeruginosa hydrodynamic flow chamber biofilms.
authors.affiliation: Center for Systems Microbiology, DTU-Systems Biology, Building 301, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Jochumsen
authors.affiliation: Center for Systems Microbiology, DTU-Systems Biology, Building 301, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Systems Microbiology, DTU-Systems Biology, Building 301, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Molin
authors.affiliation: Center for Systems Microbiology, DTU-Systems Biology, Building 301, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Folkesson
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D004251:DNA Transposable Elements; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D008070:Lipopolysaccharides / Q000378:metabolism; D016254:Mutagenesis, Insertional; D009876:Operon / Q000187:drug effects / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D008070:Lipopolysaccharides; C466663:novispirin G10