title: Modulating Acinetobacter baumannii biofilm development with molecules containing 3,4,5-trimethoxy-N,N',N'-trimethylbenzohydrazide moiety.
abstract: In recent years, Acinetobacter baumannii has emerged as a major cause of nosocomial infections, including infections of implanted medical devices. The treatment of infections caused by A. baumannii has been severely hampered due to their frequent resistance to currently available antibiotics, and most importantly the ability of A. baumannii to form biofilms, which plays a significant role in both persistence and antibiotic resistance. The inherent resistance of A. baumannii biofilms to host defenses and antimicrobial agents necessitates the search for novel approaches to deter biofilm formation. Here, we report our findings on nine compounds identified from structure-activity relationship (SAR) studies on an antibiofilm compound LP3134 that was reported earlier by Biofouling2014, 30, 17. Compounds were evaluated for antibiofilm and anti-adherence activities against A. baumannii. The ability of the compounds to prevent biofilm development on urinary catheters was studied. Growth curve experiments indicated that compounds did not affect the planktonic growth of A. baumannii. All compounds inhibited A. baumannii biofilm development as well as impacting early adhesion on abiotic surfaces. Seven compounds were able to deter biofilm development on silicone catheters. Due to the continued rise of emerging multidrug-resistant A. baumannii, results from this study provide foundation for further development of these molecules to treat A. baumannii infections in wounds and medical devices.
authors.affiliation: Wound Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Electronic address: skarthik78in@gmail.com.
authors.forename: Karthik
authors.initials: K
authors.lastname: Sambanthamoorthy
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hickman
authors.affiliation: Molbox, 8115 Fenton Street, Suite 304, Silver Spring, MD 20910, USA.
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Pattabiraman
authors.affiliation: Wound Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Palys
authors.affiliation: Wound Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Wagar
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D000067996:RAW 264.7 Cells; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D006834:Hydrazines
keywords: Acinetobacter; Antibacterial; Biofilm; Small molecules