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Nature study: A novel family of antibiotics against tuberculosis and salmonella target pathways active in cancer.

Researchers have discovered new ways to fight bacterial infections including extensively drug-resistant tuberculosis. The work will be published in the journal Nature on 29 November.

The research led by Dr. Jacques Neefjes from the Netherlands Cancer Institute, with collaboration of Dr. Tom Ottenhoff from the Leiden University Medical Center and Dr. Hermen Overkleeft from the Leiden University Institute of Chemistry, shows that pathways commonly found in cancer cells are also modified by pathogenic bacteria. It is likely that the discovery will lead to new drugs against cancer and tuberculosis.

The Dutch groups have developed chemical compounds which can greatly reduce the bacterial loads within infected human cells (such as Mycobacteria tuberculosis and Salmonella typhimurium). The chemical compounds they generated inhibit PKB/Akt1 enzymes in cells, enzymes which are also upregulated in various cancers. It appears that pathogenic bacteria seize control of PKB/Akt1 to evade immune degradation. Inhibiting the PKB/Akt1 enzyme thus forces the bacteria back into the degradation pathway to be eliminated.

PKB/Akt1 is the focus of cancer research at present since it has been shown to stimulate the growth of cancer cells. Discovering that bacteria utilize PKB/Akt1 in order to survive, sheds some light onto mechanisms that lead to cancer development following chronic bacterial infections in some patients.

“Many anti-cancer drugs originate from antibiotic discovery attempts. Pharmaceutical companies are currently developing specific PKB/Akt1 inhibitors. It is feasible that these inhibitors may well work against bacterial infections also”, says Dr. Jacques Neefjes.

This month, the World Health Organization (WHO) sounded the alarm because of a severe increase in multi and extensively drug-resistant (MDR and XDR) Mycobacterium tuberculosis infected countries. For MDR and XDR infected patients, current antibiotic therapy is inefficient or ineffective. New antibiotic therapies are therefore urgently needed.

This research was supported by the Netherlands Organization for Scientific Research (NWO), the Dutch Cancer Society (KWF) and an EEC network grant.

Frederique Melman | alfa
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