Methods of treating biofilm infections comprising administering inhibitors of myeloid-derived suppressor cells
Compositions and methods for preventing, ameliorating or treating biofilm infections are provided, including biofilms comprising at least one Pseudomonad or Staphylococcus , such as S. aureus . The biofilm infections may be associated with artificial joints, prostheses or implants.
1. A method of treating a biofilm infection comprising administering a therapeutically effective amount of an isolated inhibitor of a myeloid-derived suppressor cell selected from the group consisting of a Signal Transducer and Activator of Transcription 3- (STAT3)-targeted small interfering RNA (siRNA), a Janus kinase (JAK) inhibitor, an anti-CD15 (stage-specific embryonic antigen (SSEA-1)), an anti-CD33, an anti-CD34, an anti-CD66b, an anti-CD162, an anti-MRP-14 (anti-S100 calcium binding protein A9 (anti-S100A9)), an anti-nuclear factor kappa B p50 subunit (anti-NF-kB (p50)) antibody, an anti-Src homology 2 domain containing inositol polyphosphate 5-phosphatase 1 (anti-SHIP-1) antibody, an anti-STAT1 antibody, an indoleamine 2,3-dioxygenase (IDO) inhibitor other than rosmarinic acid, a nuclear factor erythroid 2-related factor 2 (Nrf-2) activator, an interleukin 10 (IL-10) inhibitor, an IL-10 receptor inhibitor, an arginase inhibitor, stattic, galiellalactone, GLG-101, GLG-202, GLG-302, GLG-401 and OPB-31121.
2. The method of claim 1 wherein the myeloid-derived suppressor cell (MDSC) is a CD11b + Ly-6G/Ly-6C + (Gr-1 + ) MDSC.
3. The method of claim 1 wherein the arginase inhibitor is C-201 or C-301; or the IDO inhibitor is INCB24360, norharmane, 1-methyltryptophan, a tryptophan derivative, Indoximod, or NLG919; or the JAK inhibitor is AZD1480, tofacitinib, ruxolitinib, baricitinib, decernotinib, GPLGO34, CEP-701 (lestaurtinib), INCB39110, INCB16562, INCB47986, SB1518 (pacritinib), SAR302503, XL019, or NVP-BSK805; or the Nrf-2 activator is RTA-408.
4. The method of claim 1 wherein the biofilm is associated with an artificial substance in vivo.
5. The method of claim 1 wherein the biofilm infection is a Staphylococcus infection or a Pseudomonas infection.
6. The method of claim 5 wherein the Staphylococcus infection is a methicillin-resistant Staphylococcus aureus (MRSA) infection.
7. A method of treating a biofilm infection comprising administering a therapeutically effective amount of an isolated inhibitor of a myeloid-derived suppressor cell, wherein the isolated inhibitor of a myeloid-derived suppressor cell is GLG-302.