PMID- 28165020
OWN - NLM
STAT- MEDLINE
DCOM- 20181113
LR  - 20181211
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Feb 6
TI  - A potent synthetic inorganic antibiotic with activity against drug-resistant 
      pathogens.
PG  - 41999
LID - 10.1038/srep41999 [doi]
LID - 41999
AB  - The acronymously named "ESKAPE" pathogens represent a group of bacteria that 
      continue to pose a serious threat to human health, not only due to their 
      propensity for repeated emergence, but also due to their ability to "eskape" 
      antibiotic treatment. The evolution of multi-drug resistance in these pathogens 
      alone has greatly outpaced the development of new therapeutics, necessitating an 
      alternative strategy for antibiotic development that considers the evolutionary 
      mechanisms driving antibiotic resistance. In this study, we synthesize a novel 
      inorganic antibiotic, phosphopyricin, which has antibiotic activity against the 
      Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and 
      vancomycin-resistant Enterococcus faecium (VRE). We show that this potent 
      antibiotic is bactericidal, and exhibits low toxicity in an acute dose assay in 
      mice. As a synthetic compound that does not occur naturally, phosphopyricin would 
      be evolutionarily foreign to microbes, thereby slowing the evolution of 
      resistance. In addition, it loses antibiotic activity upon exposure to light, 
      meaning that the active antibiotic will not accumulate in the general environment 
      where strong selective pressures imposed by antibiotic residuals are known to 
      accelerate resistance. Phosphopyricin represents an innovation in antimicrobials, 
      having a synthetic core, and a photosensitive chemical architecture that would 
      reduce accumulation in the environment.
FAU - Hubick, Shelby
AU  - Hubick S
AD  - Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, 
      Saskatchewan, S4S0A2, Canada.
FAU - Jayaraman, Arumugam
AU  - Jayaraman A
AD  - Department of Chemistry and Biochemistry, University of Regina, 3737 Wascana 
      Parkway, Regina, Saskatchewan, S4S0A2, Canada.
FAU - McKeen, Alexander
AU  - McKeen A
AD  - Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, 
      Saskatchewan, S4S0A2, Canada.
FAU - Reid, Shelby
AU  - Reid S
AD  - College of Pharmacy and Nutrition, University of Saskatchewan, 104 Clinic Place, 
      Saskatoon, Saskatchewan, S7N2Z4, Canada.
FAU - Alcorn, Jane
AU  - Alcorn J
AD  - College of Pharmacy and Nutrition, University of Saskatchewan, 104 Clinic Place, 
      Saskatoon, Saskatchewan, S7N2Z4, Canada.
FAU - Stavrinides, John
AU  - Stavrinides J
AD  - Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, 
      Saskatchewan, S4S0A2, Canada.
FAU - Sterenberg, Brian T
AU  - Sterenberg BT
AD  - Department of Chemistry and Biochemistry, University of Regina, 3737 Wascana 
      Parkway, Regina, Saskatchewan, S4S0A2, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170206
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Inorganic Chemicals)
RN  - 0 (Organometallic Compounds)
RN  - 0 (phosphopyricin)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*chemistry/*pharmacology
MH  - Bacteria/*drug effects/isolation & purification
MH  - Bacterial Infections/*drug therapy/microbiology
MH  - Drug Resistance, Multiple, Bacterial/*drug effects
MH  - Female
MH  - Inorganic Chemicals/*chemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microbial Sensitivity Tests
MH  - Organometallic Compounds/*chemistry/*pharmacology
PMC - PMC5292749
COIS- The authors declare no competing financial interests.
EDAT- 2017/02/07 06:00
MHDA- 2018/11/14 06:00
PMCR- 2017/02/06
CRDT- 2017/02/07 06:00
PHST- 2016/11/15 00:00 [received]
PHST- 2017/01/03 00:00 [accepted]
PHST- 2017/02/07 06:00 [entrez]
PHST- 2017/02/07 06:00 [pubmed]
PHST- 2018/11/14 06:00 [medline]
PHST- 2017/02/06 00:00 [pmc-release]
AID - srep41999 [pii]
AID - 10.1038/srep41999 [doi]
PST - epublish
SO  - Sci Rep. 2017 Feb 6;7:41999. doi: 10.1038/srep41999.