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13.04.2015, admin  
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Tough pathogens, such as anthrax and MRSA, depend on nitric oxide to defend themselves against antibiotic drugs, according to recent research. Although doctors have prescribed antibiotics to treat infections for well over 50 years, many bacteria have developed resistance to these treatments, prompting drug companies to spend millions of dollars developing alternative forms of the drugs.
Although the nitric oxide molecule is the true culprit — it interrupts the destructive chemical pathway launched by an antibiotic — Nudler believes the best offense against bacteria will be attacking the compound’s production site, known as nitric oxide synthase, or NOS. Treating bacterial infections with cocktails of traditional antibiotics and NOS inhibitors to prevent nitric oxide formation will be more efficient than designing entirely new drugs, suggests Nudler. To test this proposed therapy, Nudler’s team has already moved on to testing drug combinations in mice, with the help of collaborators from the University of California, San Diego. The recent studies, which both demonstrated nitric oxide’s role in helping bacteria stave off the effects of antibiotics and paved the way for its potential therapeutic applications, have excited Nudler’s colleagues. While antibiotics have long been used to fight bacteria, exactly how the drugs caused cell death remained a mystery until 2007, when Collins’ group demonstrated that many antibiotics rely on destructive oxidizing agents in order to ravage the bacteria from the inside out.

But if this was the poison, the question remained: what did the bacteria use as an antidote to help themselves stay alive? With his studies of a dual-drug system already underway in mice, Nudler believes they can quickly evaluate this new strategy.
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Targeting this line of defense may lead to new tactics for fighting even the nastiest bacterial infections.
Even more troublesome have been specific bacteria, including strains of Staphylococcus, which defy most known antibiotics. Drug developers have already identified and tested molecules that block similar NOS enzymes in humans. An important advantage of this approach is that each of the individual drugs that make up the new therapy have already undergone independent tests for human safety; a combined therapy should therefore not require the arduous drug screening that entirely new antibiotics have to endure.

The identification of nitric oxide’s role in bacterial defense has provided a valuable answer, one that might make researchers reevaluate antibiotic design. Yet, with the new discovery of how bacteria defend themselves with nitric oxide, scientists now hope that by merely blocking the site of nitric oxide production in bacteria they can make traditional antibiotics much more potent against even incredibly virulent infections.
Although these particular drugs were designed to target the human nitric oxide pathways that are involved in blood pressure disorders, the same technology may be tuned to specifically target bacteria.

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