Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections
被引:123
|
作者:
Thangamani, Shankar
论文数: 0引用数: 0
h-index: 0
机构:
Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USAPurdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA
Thangamani, Shankar
[1
]
Younis, Waleed
论文数: 0引用数: 0
h-index: 0
机构:
Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USAPurdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA
Younis, Waleed
[1
]
Seleem, Mohamed N.
论文数: 0引用数: 0
h-index: 0
机构:
Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USAPurdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA
Seleem, Mohamed N.
[1
]
机构:
[1] Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA
Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.
机构:
Sound Shore Med Ctr Westchester, Dept Med, New Rochelle, NY USALong Isl Univ, Dept Biomed Sci, Brookville, NY USA
Mihu, Mircea Radu
Martinez, Luis R.
论文数: 0引用数: 0
h-index: 0
机构:
Long Isl Univ, Dept Biomed Sci, Brookville, NY USA
Albert Einstein Coll Med, Div Infect Dis, Dept Med, Bronx, NY 10467 USA
Albert Einstein Coll Med, Div Infect Dis, Dept Microbiol & Immunol, Bronx, NY 10467 USALong Isl Univ, Dept Biomed Sci, Brookville, NY USA
机构:
Childrens Hosp Michigan, Dept Pharm, 3901 Beaubien Blvd, Detroit, MI 48201 USA
Childrens Hosp Michigan, Detroit Med Ctr, Detroit, MI 48201 USAChildrens Hosp Michigan, Dept Pharm, 3901 Beaubien Blvd, Detroit, MI 48201 USA
Molloy, Leah
论文数: 引用数:
h-index:
机构:
Abdulhamid, Ibrahim
Srivastava, Ruma
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Michigan, Detroit Med Ctr, Detroit, MI 48201 USA
Wayne State Univ, Div Pulm Med, Detroit, MI USA
Wayne State Univ, Div Infect Dis, Detroit, MI USAChildrens Hosp Michigan, Dept Pharm, 3901 Beaubien Blvd, Detroit, MI 48201 USA
Srivastava, Ruma
Ang, Jocelyn Y.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Michigan, Detroit Med Ctr, Detroit, MI 48201 USA
Wayne State Univ, Div Infect Dis, Detroit, MI USA
Wayne State Univ, Sch Med, Detroit, MI USAChildrens Hosp Michigan, Dept Pharm, 3901 Beaubien Blvd, Detroit, MI 48201 USA
机构:
Autonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, SpainAutonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, Spain
Montero, M.
Horcajada, J. P.
论文数: 0引用数: 0
h-index: 0
机构:
Autonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, SpainAutonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, Spain
Horcajada, J. P.
Sorli, L.
论文数: 0引用数: 0
h-index: 0
机构:
Autonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, SpainAutonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, Spain
Sorli, L.
Alvarez-Lerma, F.
论文数: 0引用数: 0
h-index: 0
机构:
Autonomous Univ Barcelona, Intens Care Unit, Hosp del Mar, Barcelona 08003, SpainAutonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, Spain
Alvarez-Lerma, F.
Grau, S.
论文数: 0引用数: 0
h-index: 0
机构:
Autonomous Univ Barcelona, Dept Pharm, Hosp del Mar, Barcelona 08003, SpainAutonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, Spain
Grau, S.
Riu, M.
论文数: 0引用数: 0
h-index: 0
机构:
CIBERESP, Hlth Serv Evaluat & Clin Epidemiol Dept, Hosp del Mar, Barcelona, SpainAutonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, Spain
Riu, M.
Sala, M.
论文数: 0引用数: 0
h-index: 0
机构:
CIBERESP, Hlth Serv Evaluat & Clin Epidemiol Dept, Hosp del Mar, Barcelona, SpainAutonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, Spain
Sala, M.
Knobel, H.
论文数: 0引用数: 0
h-index: 0
机构:
Autonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, SpainAutonomous Univ Barcelona, Dept Internal Med & Infect Dis, Hosp del Mar, Barcelona 08003, Spain
机构:
CSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India
Acad Sci & Innovat Res, Ghaziabad 201002, IndiaCSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India
Imran, Mohmmad
Ahmad, Mohammad Naiyaz
论文数: 0引用数: 0
h-index: 0
机构:
CSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, IndiaCSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India
Ahmad, Mohammad Naiyaz
Dasgupta, Arunava
论文数: 0引用数: 0
h-index: 0
机构:
CSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India
Acad Sci & Innovat Res, Ghaziabad 201002, IndiaCSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India
Dasgupta, Arunava
Rana, Preeti
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Pharmaceut Educ & Res, Dept Proc & Med Chem, NH 9,Balanagar Main Rd,Kukatpally Ind Estate, Hyderabad 500037, Telangana, IndiaCSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India
Rana, Preeti
论文数: 引用数:
h-index:
机构:
Srinivas, Nanduri
Chopra, Sidharth
论文数: 0引用数: 0
h-index: 0
机构:
CSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India
Acad Sci & Innovat Res, Ghaziabad 201002, IndiaCSIR Cent Drug Res Inst, Div Microbiol, Sect 10,Sitapur Rd, Lucknow 226031, Uttar Pradesh, India
机构:
Univ Hosp Geneva, Infect Control Program, Geneva, Switzerland
Fac Med, Geneva, SwitzerlandUniv Hosp Geneva, Infect Control Program, Geneva, Switzerland
Harbarth, Stephan
Bonten, Marc J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands
Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, NetherlandsUniv Hosp Geneva, Infect Control Program, Geneva, Switzerland