Current research in the laboratory focuses on drug discovery against bacterial infections. Antibiotic resistance coupled with the paucity of new antibiotics in the pipeline represents a global health threat. If no action is taken to counter this threat more people will die of infectious diseases than of heart disease or cancer.
We have discovered small-molecule antivirulence agents against MRSA and other Gram-positive pathogens. These potential drugs do not kill the pathogen as antibiotics do, but disarm the pathogen of its deadly weapons, the toxins. It is the toxins that cause disease. In the absence of toxins, the pathogen is rendered harmless.
Methicillin-Resistant Staphylococcus Aureus (MRSA) is the most prevalent bacterial pathogen in the developed world causing an annual mortality rate of 20,000 in the US alone. MRSA is resistant to most antibiotics and it is widespread in hospitals as well as in the community where it infects even healthy people such as athletes. Untreated MRSA infections can lead to sepsis, a condition with a high rate of mortality.
The discoveries have been patented. Case Western Reserve University has licensed the intellectual property to biopharmaceutical company, Q2Pharma, Ltd. to conduct preclinical studies towards FDA approval for clinical studies to introduce this new game-changing therapy into the clinic.
- Greenberg, Kuo, Jankowsky, Long, Hager, Bandi, Ma, Manoharan, Shoham Y, Harte, Ghannoum and Shoham M.
“Small-molecule AgrA inhibitors F12 and F19 act as antivirulence agents against Gram-positive pathogens.”
Scientific Reports Accepted for publication; available online 10/1/18 (2018).
- Flückiger R., Cocuzzi E., Nagaraj R.H., Shoham M., Kern T.S., Medof M.E.
“DAF in diabetic patients is subject to glycation/inactivation at its active site residues.”
Mol Immunol. 93:246-252 (2018).
- Shoham M., Greenberg M.
“Preventing the spread of infectious diseases: antivirulents versus antibiotics.”
Future Microbiol. 12:365-368 (2017).
- Kubera A., Thamchaipenet A., Shoham M.
“Biofilm inhibitors targeting the outer membrane protein A of Pasteurella multocida in swine.”
Biofouling 33(1):14-23 (2017).
- Park J., Schlederer M., Schreiber M., Ice R., Merkel O., Bilban M., Hofbauer S., Kim S., Addison J., Zou J., Ji C., Bunting S.T., Wang Z., Shoham M., Huang G., Bago-Horvath Z., Gibson L.F., Rojanasakul Y., Remick S., Ivanov A., Pugacheva E., Bunting K.D., Moriggl R., Kenner L., Tse W.
“AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.”
Oncotarget. 6(24):20697-710 (2015).
- Kuo D., Yu G., Hoch W., Gabay D., Long L., Ghannoum M., Nagy N., Harding C. V., Viswanathan R., and Shoham M.
“Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to beta-lactam antibiotics”
Antimicrob Agents Chemother 59 (3): 1512-8 (2015).
- Yu G., Kuo D., Shoham M., and Viswanathan R.
“Combinatorial synthesis and in vitro evaluation of a biaryl hydroxyketone library as antivirulence agents against MRSA”
ACS Comb Sci 16 (2): 85-91 (2014).
- Khodaverdian V., Pesho M., Truitt B., Bollinger L., Patel P., Nithianantham S., Yu G., Delaney E., Jankowsky E., and Shoham M.
“Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus”
Antimicrob Agents Chemother 57 (8): 3645-52 (2013).
- Shoham M.
“Antivirulence agents against MRSA”
Future Med Chem 3 (7): 775-7 (2011).