title: Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury.
abstract: Classical antimicrobial drugs target proliferation and therefore place microbes under extreme selective pressure to evolve resistance. Alternative drugs that target bacterial virulence without impacting survival directly offer an attractive solution to this problem, but to date few such molecules have been discovered. We previously discovered a widespread group of bacterial adhesins, termed Multivalent Adhesion Molecules (MAMs) that are essential for initial binding of bacteria to host tissues and virulence. Thus, targeting MAM-based adherence is a promising strategy for displacing pathogens from host tissues and inhibiting infection. Here, we show that topical application of polymeric microbeads functionalized with the adhesin MAM7 to a burn infected with multidrug-resistant Pseudomonas aeruginosa substantially decreased bacterial loads in the wound and prevented the spread of the infection into adjacent tissues. As a consequence, the application of this adhesion inhibitor allowed for vascularization and wound healing, and maintained local and systemic inflammatory responses to the burn. We propose that MAM7-functionalized microbeads can be used as a topical treatment, to reduce bacterial attachment and hence prevent bacterial colonization and infection of wounds. As adhesion is not required for microbial survival, this anti-infective strategy has the potential to treat multidrug-resistant infections and limit the emergence of drug-resistant pathogens.
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Huebinger
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Stones
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Marcela
authors.initials: M
authors.lastname: de Souza Santos
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Carlson
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Juquan
authors.initials: J
authors.lastname: Song
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Diana Pereira
authors.initials: DP
authors.lastname: Vaz
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Keen
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wolf
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Orth
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School at Houston, Houston, TX, 77030, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Krachler
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects*; D058491:Bacterial Load / Q000187:drug effects; D002056:Burns / Q000382:microbiology*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008297:Male; D008863:Microspheres; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects; D014946:Wound Infection / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents