I've read a lot of stories about antibiotic-resistant infections, but this New Yorker piece by Jerome Groopman called "Superbugs" stands out.
Frederick Ausubel, a bacterial geneticist at the Massachusetts General Hospital, in Boston, is searching for drugs to combat bacterial virulence, using tiny animals like worms, which have intestinal cells that are similar to those in humans, and which are susceptible to lethal microbial infection. The worm that Ausubel is studying, Caenorhabditis elegans, is one and a half millimetres in length. "You are probably going to have to screen millions of compounds and you can't screen millions of infected mice," Ausubel said. "So our approach was to find an alternative host that could be infected with human pathogens which was small enough and cheap enough to be used in drug screens. What's remarkable is that many common human pathogens, including Staphylococcus and Pseudomonas, will cause intestinal infection and kill the worms. So now you can look for a compound that cures it, that prevents the pathogen from killing the host." Ausubel first screened some six thousand compounds by hand and found eight, none of them traditional antibiotics, that may protect the worms. He is also attempting, among other potential solutions, to find a compound that would block what is called "quorum sensing," in which bacteria release small molecules to communicate with one another and signal when a critical mass is present. Once this quorum is reached, the bacteria turn on their virulence genes. "Bacteria don't want to alert their host that they are there by immediately producing virulence factors which the host would recognize," triggering the immune system, Ausubel explained. "When they reach a certain quorum, there are too many of them for the host to do anything about it." Bonnie Bassler, a molecular biologist at Princeton University, has recently shown that it is through quorum sensing that cholera bacteria are able to accumulate in the intestines and release toxins that can be fatal; Pseudomonas is also known to switch on its virulence genes in response to signals from quorum sensing.