Microbial drug resistance is a real and growing problem, but drugmakers face disincentives: a plethora of products already on the market, the difficulty of differentiating drugs, and the habit of reserving truly new drugs for emergencies. Big Pharmas are backing out, creating opportunities for small companies who feel they can play successfully. But lack of interest from large partners means biotechs can't access the assets those firms hold, so many start-ups are pairing up with peers. Some firms are building businesses around an abundance of targets derived through genomics. But others are deliberately avoiding working with novel genetic code and instead studying whole cells and physiological changes in organisms. Many firms are addressing the lack of chemical diversity against targets. Some of these are pursuing diversity through natural products like marine microbes, insisting they'll fare better than earlier firms did, in part because of technological advances. Others are trying to create diversity synthetically, by taking structural approaches to understanding targets new and old, as well as compounds. Crystallography, in silico libraries, computational models and mass spectroscopy are key tools in iterative development processes that remain unproven in the anti-infectives field. Some firms are seeking to minimize the risks of novelty, by putting their efforts into developing new versions of antibiotics that worked well before resistance grew. No matter what technological approach start-ups take to developing antibiotics, all face similar challenges external to themselves-primarily in regulatory affairs and funding, but also in hunting Big Pharma partnerships.

Quorex Pharmaceuticals has discovered a regulatory molecule and signaling pathway that permits bacterial cells to sense when they have achieved the population density (a quorum) needed to initiate the successful infection of a host. It is developing compounds that disrupt that communication system, which is found in a range of pathogens, to prevent infection.

A preview of the emerging health care companies profiled in the current issue of Start-Up. This month's profile group, Cardiovascular Devices, features profiles of CardioClasp Inc., CardioNet Inc. and Hearten Medical Inc. Plus these selected Start-Ups across Health Care: BioVex Ltd., HealthScreen America Inc., LabPortal Inc., Quorex Pharmaceuticals Inc. and Raven Biotechnologies Inc.