Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury

Ryan M. Huebinger, Daniel H. Stones, Marcela De Souza Santos, Deborah L. Carlson, Juquan Song, Diana Pereira Vaz, Emma Keen, Steven E. Wolf, Kim Orth, Anne Marie Krachler

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article number39341
JournalScientific Reports
Volume6
DOIs
StatePublished - Dec 20 2016

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Pseudomonas Infections
Pseudomonas aeruginosa
Microspheres
Virulence
Wounds and Injuries
Infection
Bacterial Adhesins
Pharmaceutical Preparations
Bacterial Load
Bacterial Infections
Wound Healing
Bacteria

ASJC Scopus subject areas

  • General

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Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury. / Huebinger, Ryan M.; Stones, Daniel H.; De Souza Santos, Marcela; Carlson, Deborah L.; Song, Juquan; Vaz, Diana Pereira; Keen, Emma; Wolf, Steven E.; Orth, Kim; Krachler, Anne Marie.

In: Scientific Reports, Vol. 6, 39341, 20.12.2016.

Research output: Contribution to journalArticle

Huebinger, Ryan M. ; Stones, Daniel H. ; De Souza Santos, Marcela ; Carlson, Deborah L. ; Song, Juquan ; Vaz, Diana Pereira ; Keen, Emma ; Wolf, Steven E. ; Orth, Kim ; Krachler, Anne Marie. / Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury. In: Scientific Reports. 2016 ; Vol. 6.
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