Thanks to the invention of antibiotics, 20th-century medicine virtually eliminated tuberculosis, polio, leprosy and many other once-common infectious diseases. In the 21st century, however, the advent of drug-resistant strains of tuberculosis and other killer infections — sometimes called "superbugs" — has raised fears of a frightening comeback by some of these same diseases.

So, researchers are trying a different approach. A new treatment strategy targets the so-called "virulence factors" that bacteria need to thrive once they have infected a host and offers a powerful alternative to antibiotics.

"We have developed the first inhibitor of a key small molecule from Mycobacterium tuberculosis and Mycobacterium leprae (which causes leprosy) utilized to subvert human host's defenses and damage and invade human host's cells during infection," explains senior author Dr. Luis Quadri, Associate Professor of Microbiology and Immunology at Weill Cornell Medical College in New York City. "Our next step is to explore whether this inhibitor can stop these pathogens from multiplying in a mouse host, curtailing infection."

The findings — published online and in the January 26 edition of Chemistry and Biology — may herald a massive breakthrough in infectious disease research. "We are moving beyond antimicrobials such as antibiotics, which kill the bacterium directly, to anti-infectives, that may have no effect against the pathogen in the test tube but which do compromise its ability to infect and spread in the host," Quadri explains. "We believe that the expansion of the drug armamentarium to include such anti-infective drugs could help the fight against multi-drug resistant infection that has become such a challenge today."

According to the WHO, tuberculosis kills nearly two million people every year. New drug-resistant strains of the disease — as well as even more dangerous, so-called extensive-drug-resistant (XDR) strains of the bug — are discovered each year.

"I believe that drugs targeting virulence factors are just one component of the paradigm shift in the antimicrobial drug discovery for the 21st century — one that will offer patients more options in the fight against truly global killers," Dr. Quadri says.