Manganese Complex New Weapon Against Antimicrobial Resistance

New classes of compounds, such as metal-complexes, can be used as alternatives to or to supplement traditional antibiotics, which have become ineffective due to antimicrobial resistance, researchers at University of Surrey have found.

Antimicrobial resistance is the ability of a microorganism, such as bacterium or virus, to resist the effects of an antimicrobial, which was originally effective for treatment of infections caused by it. Anti-microbial resistance is a mounting threat – 700,000 people around the world each year die as a result of drug-resistant infections including tuberculosis, HIV and malaria.

A review of anti-microbial resistance has predicted that if no action is taken, drug-resistant infections will kill 10 million people a year by 2050. England’s Chief Medical officer, Dame Sally Davies has said that such resistance to antibiotics could mean the end of modern medicine.

Manganese Tricarbonyl Complex

The researchers discovered that the antibacterial activity of the licensed antibiotic colistin, was significantly enhanced when used in combination with a new manganese tricarbonyl complex. The combination was far more effective in killing multidrug-resistant bacteria than colistin alone.

The activity was also confirmed in aninsectmodel of infection, where survival rates of 87% were observed in those treated with the combination, compared to 50% survival in those given colistin alone. This work highlights the activity of the first of many antimicrobials under development, with sister antimicrobials even more active than the first.

Time-kill curve of [Mn(CO)3(tpa-κ3N)]Br, colistin and combination

Time-kill curve of [Mn(CO)3(tpa-κ3N)]Br, colistin and combination of both agents (x1 MIC + 0.5 MIC) versus APEC strain a) 99/12 and b) 236/12 over 24 h.
Credit: Jonathan Betts et al.

Lead author Dr Jonathan Betts, from the University of Surrey, said:

“Antimicrobial resistance is a constant threat, as bacteria continue to evolve at a rapid pace. This makes it very difficult for us to treat bacterial diseases, as many antibiotics are becoming redundant, limiting the treatments available to people and animals.

However, by combining these drugs, in our case with a novel metal-complex, we could extend their lifespan and effectiveness, helping us tackle this growing threat. Antibiotics which are no longer effective could potentially be reactivated when used with this compound, providing medical professionals greater options in treating diseases.”

The work was funded by the Biotechnology and Biological Sciences Council (BBSRC).

Betts J, Nagel C, Schatzschneider U, Poole R, La Ragione RM (2017)
Antimicrobial activity of carbon monoxide-releasing molecule [Mn(CO)3(tpa-κ3N)]Br versus multidrug-resistant isolates of Avian Pathogenic Escherichia coli and its synergy with colistin
PLoS ONE12(10): e0186359. https://doi.org/10.1371/journal.pone.0186359

Top Image: University of Surrey