New way to fight antibiotic-resistant bacteria: Target human cells instead

Dec 11, 2013
New way to fight antibiotic-resistant bacteria: Target human cells instead

As more reports appear of a grim "post-antibiotic era" ushered in by the rise of drug-resistant bacteria, a new strategy for fighting infection is emerging that targets a patient's cells rather than those of the invading pathogens. The technique interferes with the way that the pathogens take over a patient's cells to cause infection. This approach, published in the journal ACS Chemical Biology, could help address the world's growing problem of antibiotic-resistant "super bugs."

Huib Ovaa, Jacques Neefjes and colleagues explain that the problem of antibiotic-resistant bacteria poses a major . Health organizations have warned that unless alternatives to classic antibiotics are developed, even infections from minor scrapes could become deadly. Pharmaceutical companies are working on only a few , and they all take the same approach – attack the bacteria. But resistance is always a possibility. To get around this, researchers are now looking more closely at how bacteria co-opt the cells they invade for survival. These researchers previously reported that at least one set of host cell proteins, called kinases, can control bacterial growth. Ovaa and Neefjes' team decided to look at another class of proteins, called phosphatases, that act in the opposite way from kinases to see if inhibiting them would have a similar effect.

In lab tests, they identified phosphatases in human cells that are involved in bacterial survival. They also identified small molecules, or potential drugs, that could stop those phosphatases from working. Those molecules, which could form a new class of antibiotics, successfully stopped Salmonella, their test bacteria, from growing. Because this approach jams the machinery rather than directly attacking the bacteria, the chances of developing resistance could be very low, say the researchers. They also say that the research shows that phosphatases, like kinases, could be general targets for drug development.

Explore further: Evolution winning in bacteria vs antibiotics arms race

More information: "Integrating Chemical and Genetic Silencing Strategies To Identify Host Kinase-Phosphatase Inhibitor Networks That Control Bacterial Infection" ACS Chem. Biol., Article ASAP. DOI: 10.1021/cb400421a

Abstract
Every year three million people die as a result of bacterial infections, and this number may further increase due to resistance to current antibiotics. These antibiotics target almost all essential bacterial processes, leaving only a few new targets for manipulation. The host proteome has many more potential targets for manipulation in order to control bacterial infection, as exemplified by the observation that inhibiting the host kinase Akt supports the elimination of different intracellular bacteria including Salmonella and M. tuberculosis. If host kinases are involved in the control of bacterial infections, phosphatases could be as well. Here we present an integrated small interference RNA and small molecule screen to identify host phosphatase-inhibitor combinations that control bacterial infection. We define host phosphatases inhibiting intracellular growth of Salmonella and identify corresponding inhibitors for the dual specificity phosphatases DUSP11 and 27. Pathway analysis places many kinases and phosphatases controlling bacterial infection in an integrated pathway centered around Akt. This network controls host cell metabolism, survival, and growth and bacterial survival and reflect a natural host cell response to bacterial infection. Inhibiting two enzyme classes with opposite activities–kinases and phosphatases–may be a new strategy to overcome infections by antibiotic-resistant bacteria.

add to favorites email to friend print save as pdf

Related Stories

A new weapon in the war against superbugs

Dec 02, 2013

In the arms race between bacteria and modern medicine, bacteria have gained an edge. In recent decades, bacterial resistance to antibiotics has developed faster than the production of new antibiotics, making ...

Antibiotics – friend and foe?

Nov 18, 2013

European Antibiotic Awareness Day is marked on the 18th November every year. This year in Norway, a seminar for health care providers about antibiotic use and resistance will be held, as well as several local events around ...

Recommended for you

Scientists develop pioneering new spray-on solar cells

10 hours ago

(Phys.org) —A team of scientists at the University of Sheffield are the first to fabricate perovskite solar cells using a spray-painting process – a discovery that could help cut the cost of solar electricity.

User comments : 0