PMID- 30556803
OWN - NLM
STAT- MEDLINE
DCOM- 20190215
LR  - 20190623
IS  - 1473-5644 (Electronic)
IS  - 0022-2615 (Linking)
VI  - 68
IP  - 2
DP  - 2019 Feb
TI  - Subinhibitory concentrations of tedizolid potently inhibit extracellular toxin
      production by methicillin-sensitive and methicillin-resistant Staphylococcus
      aureus.
PG  - 255-262
LID - 10.1099/jmm.0.000905 [doi]
AB  - PURPOSE: Potent extracellular toxins including alpha-haemolysin, Panton-Valentine
      leukocidin (PVL) and toxic-shock syndrome toxin 1 (TSST-1) significantly
      contribute to Staphylococcus aureus pathogenesis, thus, toxin suppression is a
      primary focus in treatment of staphylococcal disease. S. aureus maintains complex
      strategies to regulate toxin expression and previous data have demonstrated that 
      subinhibitory concentrations of beta-lactam antibiotics can adversely increase S.
      aureus exotoxin production. The current study evaluates the effects of
      subinhibitory concentrations of tedizolid, a second-generation oxazolidinone
      derivative, on expression of staphylococcal exotoxins in both
      methicillin-resistant and methicillin-sensitive S. aureus. METHODOLOGY: S. aureus
      exotoxin expression levels were compared at 12 and 24 h following treatment with 
      tedizolid, linezolid, nafcillin or vehicle control. RESULTS: Our findings show
      that the level of antibiotic required to alter toxin production was
      strain-dependent and corresponds with the quantity of toxin produced, but both
      tedizolid and linezolid could effectively reduce expression of alpha-haemolysin, 
      PVL and TSST-1 toxin at subinhibitory concentrations. In contrast, nafcillin
      showed less attenuation and, in some S. aureus strains, led to an increase in
      toxin expression. Tedizolid consistently inhibited toxin production at a lower
      overall drug concentration than comparator agents. CONCLUSION: Together, our data
      support that tedizolid has the potential to improve outcomes of infection due to 
      its superior ability to inhibit S. aureus growth and attenuate exotoxin
      production.
FAU - Katahira, Eva J
AU  - Katahira EJ
AD  - 1Infectious Diseases Section, Department of Veterans Affairs Medical Center,
      Boise, ID, USA.
AD  - 2Idaho Veterans Research and Education Foundation, Boise, ID, USA.
FAU - Davidson, Stephen M
AU  - Davidson SM
AD  - 2Idaho Veterans Research and Education Foundation, Boise, ID, USA.
AD  - daggerPresent address: University of Arizona, Tucson, AZ.
FAU - Stevens, Dennis L
AU  - Stevens DL
AD  - 1Infectious Diseases Section, Department of Veterans Affairs Medical Center,
      Boise, ID, USA.
AD  - 2Idaho Veterans Research and Education Foundation, Boise, ID, USA.
AD  - 3University of Washington School of Medicine, Seattle, WA, USA.
FAU - Bolz, Devin D
AU  - Bolz DD
AD  - 1Infectious Diseases Section, Department of Veterans Affairs Medical Center,
      Boise, ID, USA.
AD  - 2Idaho Veterans Research and Education Foundation, Boise, ID, USA.
LA  - eng
GR  - P20 GM109007/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20181217
PL  - England
TA  - J Med Microbiol
JT  - Journal of medical microbiology
JID - 0224131
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Enterotoxins)
RN  - 0 (Exotoxins)
RN  - 0 (Hemolysin Proteins)
RN  - 0 (Leukocidins)
RN  - 0 (Oxazolidinones)
RN  - 0 (Panton-Valentine leukocidin)
RN  - 0 (Superantigens)
RN  - 0 (Tetrazoles)
RN  - 0 (enterotoxin F, Staphylococcal)
RN  - 0 (staphylococcal alpha-toxin)
RN  - 4CNZ27M7RV (Nafcillin)
RN  - 97HLQ82NGL (tedizolid)
RN  - ISQ9I6J12J (Linezolid)
RN  - Q91FH1328A (Methicillin)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/administration & dosage/*pharmacology
MH  - Bacterial Toxins/analysis/antagonists & inhibitors/*biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Enterotoxins/analysis/antagonists & inhibitors/biosynthesis
MH  - Erythrocytes/drug effects/metabolism
MH  - Exotoxins/analysis/antagonists & inhibitors/biosynthesis
MH  - Hemolysin Proteins/analysis/antagonists & inhibitors/biosynthesis
MH  - Humans
MH  - Leukocidins/analysis/antagonists & inhibitors/biosynthesis
MH  - Linezolid/administration & dosage/pharmacology
MH  - Methicillin/*pharmacology
MH  - Methicillin Resistance
MH  - Methicillin-Resistant Staphylococcus aureus/drug effects/growth &
      development/metabolism
MH  - Microbial Sensitivity Tests
MH  - Nafcillin/administration & dosage/pharmacology
MH  - Oxazolidinones/administration & dosage/*pharmacology
MH  - Rabbits
MH  - Sheep
MH  - Staphylococcus aureus/*drug effects/growth & development/metabolism
MH  - Superantigens/analysis/biosynthesis
MH  - Tetrazoles/administration & dosage/*pharmacology
PMC - PMC6557147
OTO - NOTNLM
OT  - Staphylococcus aureus
OT  - antibiotic
OT  - bacterial
OT  - exotoxin
OT  - subinhibitory
EDAT- 2018/12/18 06:00
MHDA- 2019/02/16 06:00
CRDT- 2018/12/18 06:00
PHST- 2018/12/18 06:00 [pubmed]
PHST- 2019/02/16 06:00 [medline]
PHST- 2018/12/18 06:00 [entrez]
AID - 10.1099/jmm.0.000905 [doi]
PST - ppublish
SO  - J Med Microbiol. 2019 Feb;68(2):255-262. doi: 10.1099/jmm.0.000905. Epub 2018 Dec
      17.