LA JOLLA — Antibiotic resistance is increasing rapidly in hospitals and on the battlefield abroad. Methicillin-resistant Staphylococcus aureus (MRSA) threatens our hospital patients, and similar antibiotic-resistant bacteria threaten our soldiers in Iraq and Afghanistan. A biowarfare or terrorist threat caused by antibiotic resistance could also cause mass casualties. These are just a few of the reasons William Fenical, distinguished professor of oceanography at Scripps Institution of Oceanography (SIO), and San Diego’s Trius Therapeutics have formed a collaborative team to identify and engineer new antibiotic treatments. “We were very pleased we were actually able to do something formally with him [Fenical] with the support of DTRA,” said John Schmid, chief financial officer of Trius Therapeutics. Schmid is referring to a multi-year contract of up to $29.5 million awarded to his company and Fenical from the Defense Threat Reduction Agency (DTRA), a subdivision of the U.S. Department of Defense. “…..In Afghanistan, the military is now experiencing high levels of infections not from biowarfare, but from agents that seemingly are changing somewhat and causing infections in servicemen,” Fenical said. The partnership will use Fenical’s library of potential antibiotic candidates he and his team mined from the ocean floor. With these compounds, Trius Therapeutics will use its Focused Antisense Screening Technology (FAST) to analyze targets for antibacterial binding. The word “target” is critical to the solution of antibiotic resistance because the most common type of resistance occurs as a result of modification of a target site. Just as a keyhole is a small, carefully contoured and crafted glove into which an equally crafted key must match, an antibiotic target site must be carefully crafted so that its contours can fit together with the bacteria. It is a bit like two separate puzzle pieces with opposite shapes that must complement one another perfectly to become part of the larger picture of the puzzle. In an antibiotic resistant strain of bacteria, the target site develops a modification of structure that makes the keyhole inaccessible to the antibiotic. It would be like rust developing within a keyhole so that the key no longer fit into the hole. In such situations, the antibiotic can no longer fight a bacterial infection. Just like the MRSA patients in the hospital and soldiers on the fields of Afghanistan, modification of the target site renders a bacteria for which there is no simple cure. John Finn, chief scientific officer of Trius Therapeutics, explained how target sites and drug modification in the lab helps scientists discover new drug treatments. “A lot of times, it is a simple modification of the target site,” he said. Once a potentially active compound is identified, chemists make slight changes to the structure so that the drug is maximally potent in killing bacteria. Many naturally found products are not sufficiently potent or chemically active to combat illness in the human body. This is because in nature, their function is to compete with other microbes for survival, which has nothing to do with the human body. In nature, antibiotic precursors were never suited as in vivo drugs. Meanwhile, antibiotics are cheap and effective and often misused for illnesses caused by viral diseases for which they have no effect. It is widely believed that physicians often overprescribe antibiotics and farmers overuse them for the health of their livestock. For all of these reasons, antibiotics are susceptible to widespread resistance. The supply of new resources has not kept up with the growing need. “If we don’t do something significant in terms of increasing the effort in the discovery of new antibiotics, we could have enormous death in the United States and throughout the world,” said Fenical, director of the Center for Marine Biotechnology and Biomedicine at Scripps.
