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In recent years, a body of publications in the microbiology field has challenged all previous knowledge of how antibiotics kill bacteria. A slew of papers came out studying this phenomenon, suggesting that there is a general mechanism of killing by antibiotics, says Kim Lewis, University Distinguished Professor in the Department of Biology and director of Northeasterns Antimicrobial Discovery Center.
In recent work, biology professor Kim Lewis and senior scientist Iris Keren demonstrate that all antibiotics are not created equal. Photo by Mary Knox Merrill.
In recent years, a body of pubÂliÂcaÂtions in the microÂbiÂology field has chalÂlenged all preÂvious knowlÂedge of how antibiÂotics kill bacÂteria. A slew of papers came out studying this pheÂnomÂenon, sugÂgesting that there is a genÂeral mechÂaÂnism of killing by antibiÂotics, says Kim Lewis, UniÂverÂsity DisÂtinÂguished ProÂfessor in the DepartÂment of Biology and director of Northeasterns AntimiÂcroÂbial DisÂcovery Center.
The stanÂdard thinking at the time was that the three main classes of bacÂteÂriÂcidal antibiÂotics each had a unique way of killing bacÂteÂrial cellslike speÂcialÂized assasÂsins each trained in a single type of weaponry. But this new research sugÂgested that all antibiÂotics work the same way, by urging bacÂteÂrial cells to make comÂpounds called reacÂtive oxygen species, or ROS, which bacÂteria are natÂuÂrally susÂcepÂtible to.
If they were right it would have been an imporÂtant finding that could have changed the way we treat patients, says Iris Keren, a senior sciÂenÂtist in Lewis lab.
And thats exactly how sciÂence usuÂally works, says Lewisthrough chalÂlenges to mainÂstream thinking. But recent results reported by Lewis, Keren, and their researchÂ partÂners in an article pubÂlished Friday in the journal SciÂence sugÂgest that this alterÂnaÂtive hypothÂesis doesnt hold up. For example, even bacÂteria that are incaÂpable of making ROS are still vulÂnerÂable to antibiÂotics. FurÂther, some antibiÂotics can work their fatal magic in both aerÂobic and anaerÂobic conditionsbut reacÂtive oxygen species can only form when theres oxygen to fuel them.
We chose to do the simÂplest and most critÂical experÂiÂment aimed at falÂsiÂfying this hypothÂesis,Â adds Lewis. Killing by antibiÂotics is unreÂlated to ROS proÂducÂtion, the authors wrote. The findÂings were corÂrobÂoÂrated by UniÂverÂsity of IlliÂnois researchers in another study released on Friday .
The team treated bacÂteÂrial culÂtures with antibiÂotics in both the presÂence and absence of oxygen. Other than the gaseous enviÂronÂment, the two treatÂments were idenÂtical. There was no difÂferÂence in cell death between the two populations.
Before perÂforming these experÂiÂments, Lewis team first looked at sigÂnals of a fluÂoÂresÂcent dye, which preÂvious researchers had used as an indiÂcator for ROS levels. The team treated bacÂteÂrial cells with a variety of antibiÂotics and meaÂsured the strength of this signal. Since antibiÂotics were preÂsumed to increase ROS levels, one would have expected increased conÂcenÂtraÂtions of antibiÂotics to corÂreÂlate with stronger sigÂnals. HowÂever, Lewis group saw no such correlation.
But theres a difÂferÂence between corÂreÂlaÂtion and direct obserÂvaÂtion, Keren says. In order to supÂport their obserÂvaÂtions with unequivÂocal data, the team memÂbers physÂiÂcally sepÂaÂrated the cells that had stronger fluÂoÂresÂcent sigÂnals from those with weak sigÂnals and treated them both with the same antibiÂotics. Both popÂuÂlaÂtions sufÂfered equivÂaÂlent cell death.
The research from Lewis group demonÂstrates that, conÂtrary to curÂrent dogma, antibiÂotics apparÂently do not kill bacÂteria through inducÂtion of reacÂtive oxygen species, says Steven Projan, vice presÂiÂdent for research and develÂopÂment at iMed and head of infecÂtious disÂeases and vacÂcines at MedÂImÂmune, both subÂsidiaries of AstraZeneca. The results shown are rather clear but still leave us with the mysÂtery as to how antibacÂteÂrial drugs help infected people clear bacÂteÂrial infections. At this point, we should probÂably disÂpense with the one size fits all approach to bacÂteÂrial killing by antibiÂotics, said Projan, who was not involved in the research.
With these results, Lewis and Keren hope the field will be able to focus its efforts on underÂstanding the true mechÂaÂnisms of how antibiÂotics wipe out bacÂteria in order to effecÂtively address chronic bacÂteÂrial infecÂtions, one of the most pressing issues facing public health today.