title: Antibacterial activity of resazurin-based compounds against Neisseria gonorrhoeae in vitro and in vivo.
abstract: Neisseria gonorrhoeae is the cause of the second most common sexually transmitted bacterial infection, with ca. 80 million new cases of gonorrhoea reported annually. The recent emergence of clinical isolates resistant to the last monotherapy against this bacterium, the cephalosporins, illustrates the need for new antigonococcal agents. Here we have characterised a new group of antimicrobials based on the compound resazurin that exhibits robust activity against N. gonorrhoeae in vitro. Resazurin inhibits the growth of a broad range of N. gonorrhoeae isolates, including those resistant to multiple antibiotics. Furthermore, treatment of human endometrial cells infected with N. gonorrhoeae with resazurin significantly reduces the number of intracellular bacteria. Whilst resazurin exhibited potent in vitro antimicrobial activity, in vivo resazurin did not limit the colonisation of mice with N. gonorrhoeae following vaginal infection. The ineffectiveness of resazurin in vivo is likely due to its interaction with serum albumin, which completely diminishes its antimicrobial activity. However, treatment of mice with a resazurin analogue (resorufin pentyl ether) that maintains its antimicrobial activity in the presence of serum albumin approached a significant decrease in the percentage of mice vaginally colonised. This treatment also decreased vaginal colonisation by N. gonorrhoeae over time. Together, these data suggest that resazurin derivatives have potential for the treatment of gonorrhoea.
authors.affiliation: Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV, USA.
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Schmitt
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Connolly
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Jerse
authors.affiliation: Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV, USA.
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Detrick
authors.affiliation: Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV, USA. Electronic address: joseph.horzempa@westliberty.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Horzempa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006069:Gonorrhea / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007202:Indicators and Reagents / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000302:isolation & purification; D010078:Oxazines / Q000494:pharmacology*; D016896:Treatment Outcome; D014966:Xanthenes / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D010078:Oxazines; D014966:Xanthenes; C005843:resazurin
keywords: Antibiotic; Antimicrobial; Gonorrhoea; Neisseria gonorrhoeae; Resazurin; Resorufin