title: Opioid analgesics stop the development of clostridial gas gangrene.
abstract: Gas gangrene is a potentially fatal disease that is primarily caused by the ubiquitous, anaerobic bacteria Clostridium perfringens and Clostridium septicum. Treatment is limited to antibiotic therapy, debridement of the infected tissue, and, in severe cases, amputation. The need for new treatment approaches is compelling. Opioid-based analgesics such as buprenorphine and morphine also have immunomodulatory properties, usually leading to faster disease progression. However, here we show that mice pretreated with buprenorphine and morphine do not die from clostridial myonecrosis. Treatment with buprenorphine after the onset of infection also arrested disease development. Protection against myonecrotic disease was specific to C. perfringens-mediated myonecrosis; buprenorphine did not protect against disease caused by C. septicum infection even though infections due to both species are very similar. These data provide the first evidence of a protective role for opioids during infection and suggest that new therapeutic strategies may be possible for the treatment of C. perfringens-mediated myonecrosis.
authors.affiliation: Department of Microbiology, Monash University, Clayton, Australia.
authors.forename: Anjana
authors.initials: A
authors.lastname: Chakravorty
authors.affiliation: Department of Microbiology, Monash University, Clayton, Australia.
authors.forename: Milena M
authors.initials: MM
authors.lastname: Awad
authors.affiliation: Department of Microbiology, Monash University, Clayton, Australia.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hiscox
authors.affiliation: Department of Microbiology, Monash University, Clayton, Australia.
authors.forename: Jackie K
authors.initials: JK
authors.lastname: Cheung
authors.affiliation: Department of Microbiology, Monash University, Clayton, Australia.
authors.forename: Jocelyn M
authors.initials: JM
authors.lastname: Choo
authors.affiliation: Department of Microbiology, Monash University, Clayton, Australia.
authors.forename: Dena
authors.initials: D
authors.lastname: Lyras
authors.affiliation: Department of Microbiology, Monash University, Clayton, Australia.
authors.forename: Julian I
authors.initials: JI
authors.lastname: Rood
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D002047:Buprenorphine / Q000627:therapeutic use*; D003016:Clostridium perfringens; D005260:Female; D005738:Gas Gangrene / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000627:therapeutic use*; D009271:Naltrexone / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D009271:Naltrexone; D009020:Morphine
keywords: Clostridium perfringens; Clostridium septicum; bacterial pathogenesis; buprenorphine; clostridial myonecrosis; disease suppression; gas gangrene; host-pathogen interactions; morphine; opioids