Contact:
sales@biotechnologyforums.com to feature here

Thread Rating:
  • 0 Vote(s) - 0 Average
  • 1
  • 2
  • 3
  • 4
  • 5
Nitric oxide synthase inhibitors enhance antibiotic-mediated bacterial killing
#1
Nitric oxide synthase (NOS) inhibitor compounds, originally developed as experimental drugs for neurodegenerative disorders, may have unexpected extra applications in assisting antibiotics in the fight against drug-resistant bacteria. As we have pointed out on this forum previously, antibiotic resistance is a major public health issue and has prompted intense research efforts to attempt to understand and address it (http://www.biotechnologyforums.com/thread-2535.html; http://www.biotechnologyforums.com/thread-2540.html).

In a major study published in PNAS this week, researchers from Northwestern University in the USA used neuronal NOS (nNOS) inhibitors, known as leads compounds 1 and 2, in an attempt to boost the activity of antibiotics against Bacillus subtilis (which is a non-pathogenic strain with strong similarities to Staphylococcus aureus) and Bacillus anthracis. The strategy was suggested by a study in S. aureus, one of the few bacterial species that express bacterial NOS (bNOS). That study showed that in a bNOS mutant of the epidemic community-acquired methicillin-resistant S. aureus (MRSA) USA300 clone, the MRSA became more susceptible to killing both by immune cells such as neutrophils, by reactive oxygen species and by cell envelope-specific antibiotics including vancomycin and daptomycin. In the PNAS study, two nNOS inhibitors impeded B. subtilis growth under oxidative stress and promoted more efficient killing of B. subtilis and Bacillus anthracis by antibiotics than the antibiotic by itself. Crystal structures showed that the two compounds bind differently to the bacteria.

These studies raise hopes that nNOS inhibitors may be a lead in the fight against drug resistance in pathogens containing bNOS, such as S. aureus, as well as battling neurodegenerative disorders in which NO is overproduced by nNOS.

Sources
HOLDEN, J.K., LI, H., JING, Q., KANG, S., RICHO, J., SILVERMAN, R.B. and POULOS, T.L., 2013. Structural and biological studies on bacterial nitric oxide synthase inhibitors. Proceedings of the National Academy of Sciences, 110 (45): 18127 DOI: 10.1073/pnas.1314080110

JING, Q., LI, H., FANG, J., ROMAN, L.J., MARTáSEK, P., POULOS, T.L. and SILVERMAN, R.B., 2013. In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures. Bioorganic & medicinal chemistry, 21(17), pp. 5323-5331.

VAN SORGE, N.M., BEASLEY, F.C., GUSAROV, I., GONZALEZ, D.J., VON KÃCKRITZ-BLICKWEDE, M., ANIK, S., BORKOWSKI, A.W., DORRESTEIN, P.C., NUDLER, E. and NIZET, V., 2013. Methicillin-resistant Staphylococcus aureus bacterial nitric-oxide synthase affects antibiotic sensitivity and skin abscess development. The Journal of Biological Chemistry, 288(9), pp. 6417-6426.
Like Post Reply
  

Possibly Related Threads…
Thread
Author
  /  
Last Post



Users browsing this thread:
1 Guest(s)

Nitric oxide synthase inhibitors enhance antibiotic-mediated bacterial killing00