{"id":91,"date":"2015-11-03T12:52:55","date_gmt":"2015-11-03T17:52:55","guid":{"rendered":"https:\/\/blogs.bsu.edu\/research\/?p=91"},"modified":"2019-11-19T12:43:00","modified_gmt":"2019-11-19T17:43:00","slug":"a-possible-treatment-when-antibiotics-dont-work","status":"publish","type":"post","link":"https:\/\/blogs.bsu.edu\/research\/2015\/11\/03\/a-possible-treatment-when-antibiotics-dont-work\/","title":{"rendered":"A Possible Treatment When Antibiotics Don’t Work"},"content":{"rendered":"

*Insert Videos from website*<\/h3>\n

Outstanding Researcher of the Year<\/h3>\n

Antibiotics certainly save lives, but long-term and widespread use of the drugs has caused some bacteria to adapt and become harder to kill. The\u00a0Centers for Disease Control and Prevention<\/a>\u00a0(CDC) say that 2 million people become infected with antibiotic resistant bacteria every year in the United States, and at least 23,000 of those people die as a direct result of these infections.<\/p>\n

SusanMcDowell<\/a>, professor of\u00a0biology<\/a>\u00a0and Muncie native, is working on a treatment to make antibiotics and the immune system more effective. McDowell leads a team of Ball State University professors and students, along with researchers from the\u00a0University of New Mexico\u2019s Center for Molecular Discovery<\/a>, in this collaborative effort.<\/p>\n

\u201cOur main area of interest is in trying to develop new molecules that can combat bacterial infection by mechanisms that are different than those used with antibiotic treatment,\u201d says McDowell.<\/p>\n

She and her colleagues just received a patent for a variation of a molecule called ML141. With this molecule, she hopes to develop a drug that eventually can be used alongside antibiotics to help fight infections.<\/p>\n

\u201cAntibiotics are not able to access all of the areas of our bodies where bacteria can be hiding out. So specifically, some bacteria are able to actually invade our cells, and when they\u2019re within our cells, most antibiotics are not able to get across the cell membrane or at least not at high enough concentrations to then kill the bacteria inside,\u201d McDowell explains.<\/p>\n

She says this often becomes a problem after a person has a knee or hip replacement\u2014the resistant population is able to invade the new device and cause an infection.<\/p>\n

\u201cWhat we\u2019ve been working on for several years now is an approach that blocks the ability of bacteria to invade host cells,\u201d she says. \u201cThen they remain exposed outside of the host cells, and if they are susceptible to antibiotics, then they can get killed off by the antibiotics, or if they\u2019re a resistant population, our own immune system has better access to the bacteria and is able to help clear it away better.\u201d<\/p>\n

Statins, staph, and serendipity<\/h5>\n

Before coming to Ball State in 2003, McDowell was conducting postdoctoral research at Eli Lilly on the cardiovascular effects of statins such as Simvastatin, a prescription drug that helps lower cholesterol. She continued this research at Ball State, but unfortunately, none of her hypotheses were right.<\/p>\n

\u201cWe had an entire year\u2019s worth of negative data, meaning that every idea that we tried in that grant was wrong. I can laugh now. I was in a panic,\u201d she says with a smile.<\/p>\n

A pivotal point in McDowell\u2019s research happened when one of her students, Sharm Knecht, returned to Ball State after conducting a summer internship at IPFW. She had been studying staphylococcus aureus (staph) and asked McDowell for permission to continue her project.<\/p>\n

\u201cIn all honesty, I kept putting her off because I didn\u2019t know anything about staph. I didn\u2019t know how to grow it,\u201d says McDowell.<\/p>\n

Knecht was persistent, and eventually McDowell gave in. \u201cNow in hindsight I\u2019m very grateful for that,\u201d she says.<\/p>\n

John McKillip<\/a>, associate professor of biology, taught McDowell and Knecht how to grow staph. \u201cI made a lot of mistakes. I still make a lot of mistakes. I\u2019m not a microbiologist,\u201d says McDowell.<\/p>\n

Meanwhile, McDowell was not making any breakthroughs in her research on statins. One day, in a moment she calls \u201cserendipitous,\u201d she skimmed the literature on statins and staph. She discovered that people who were on statins for lowering cholesterol were at a decreased risk of death due to infection.<\/p>\n

\u201cThat\u2019s huge. When you\u2019re affecting death rates, then that\u2019s usually important,\u201d she says.<\/p>\n

Alongside her students, McDowell set up a simple experiment in the lab in which they pretreated some human cells with\u00a0Simvastatin<\/a>. The next day, they infected the cells with staph, and later assessed whether or not there were fewer bacteria in the cells treated with the statin compared to the control cells.<\/p>\n

\u201cI remember standing at the incubator that day physically shaking, because I knew if this experiment worked, it was a game changer,\u201d she says. \u201cIt was an incredible effect. It was a 90 percent inhibition at a clinical concentration of the statin. So that just opened a whole new direction, and that\u2019s where all of our resources went. To the best of our knowledge, we were the first to discover that statins could limit bacterial infection.\u201d<\/p>\n

What\u2019s wrong with statins?<\/h5>\n

Statins do not kill bacteria like antibiotics do. Rather, statins limit bacteria by immobilizing a host protein called CDC42. \u201cWhen it\u2019s inactivated, the host cell machinery that the bacteria usually hijack in order to invade us gets turned off. So the bacteria just get frustrated,\u201d says McDowell.<\/p>\n

However, statins affect more proteins than just CDC42, and critically ill people can have adverse effects to statins. McDowell began to wonder if another molecule existed that inhibits CDC42 only, without the adverse effects.<\/p>\n

After several dead ends and lots of help from her colleagues, McDowell tracked down a CDC42 inhibitor called ML141. This molecule was very unstable; its effects changed from week to week. McDowell began working with\u00a0Robert Sammelson<\/a>, chairperson of the Department of Chemistry, who began making alterations to ML141. In October 2015, McDowell and her colleagues received a patent for their altered molecule.<\/p>\n

Hope for a clinically available drug<\/h5>\n

When asked about her hopes for her research, McDowell says, \u201cI dream big. What we would hope is that this drug would be clinically available, so that people who are receiving antibiotics could be put on our compounds at the same time as antibiotics to try to break that infection cycle.\u201d<\/p>\n

McDowell hopes that such a compound would prevent infections in people with hip and knee replacements so they would not need additional surgeries. Her drug could also help those who get chronic infections such as strep throat. She says that chronic infections are caused by those pesky bacteria that hide out in cells, so her drug could potentially get rid of those infections for good.<\/p>\n

A great job and great students<\/h5>\n

In the lab and in the classroom, McDowell prepares her students for careers in science. Several current students and graduates shared via email the lasting impact McDowell has made on their lives.<\/p>\n

\u201cWithout the excellent start that I got working in Dr. McDowell\u2019s lab, I would not be the scientist I am today,\u201d says Robin Dewalt. \u201cUpon graduating in 2011 I left the lab feeling confident and fully prepared to start my new position. To this day, I still hear little reminders and good pointers that she taught in class and also in the lab in my head as I do my work. Her lab gave me a foundation, and luckily for me it was a solid one.\u201d<\/p>\n

\u201cI have learned how to work hard and aim high from Dr. McDowell\u2019s example. I also learned more during my time in her lab than I learned in all of my science classes combined. Dr. McDowell has inspired my love of research and teaching,\u201d says Ashley Zahrt who now teaches high school science. \u201cI teach … classes that focus heavily on biomedical science and research. Many of the techniques I teach my students were first taught to me by Dr. McDowell.\u201d<\/p>\n

Caroline Hersley is pursuing her Master\u2019s degree in biology and is participating in a co-op with Eli Lilly through Ball State. She says, \u201cWithout knowing what Dr. McDowell had taught me and gaining the experience through her lab, I would not be where I am today.\u201d<\/p>\n

\u201cI love teaching here. I have the best job,\u201d says McDowell. \u201cI have highly motivated students in each one of my classes. We\u2019re able to do really interesting things in my classes, and I\u2019ve had these great students doing research with me.\u201d<\/p>\n

\u201cEvery student who\u2019s written to congratulate me on this award, I\u2019ve had to say to them, \u2018Please know that you were the one to put the hours in at the bench. I hardly ever run an experiment. It was your work ethic, and your creative ideas.\u2019 Sometimes the students will raise a question that my brain never would have gone to. They get so invested in it. They really have redirected our work many, many, many times. Left up to me, we wouldn\u2019t be where we are today.\u201d<\/p>\n

McDowell loves teaching so much that she encourages her students to work at a similar university. \u201cIf any of you are thinking about teaching, I would hope that you find a place like Ball State, and I mean that sincerely.\u201d<\/p>\n

Acknowledgements<\/h5>\n

These accomplishments would not be possible without McDowell\u2019s colleagues Henry Akinbi, Derron Bishop, Heather Bruns, Mark Haynes, John McKillip, VJ Rubenstein, Rob Sammelson, and Larry Sklar, as well as the many hardworking students who have contributed to these efforts.<\/p>\n

McDowell extends her gratitude to the following organizations for their financial support of this research: the Ball State Honors College, the College of Sciences and Humanities, the Indiana Academy of Science, the Lilly Foundation, The National Institutes of Health, the National Science Foundation, and Sponsored Projects Administration.<\/p>\n","protected":false},"excerpt":{"rendered":"

*Insert Videos from website* Outstanding Researcher of the Year Antibiotics certainly save lives, but long-term and widespread use of the drugs has caused some bacteria to adapt and become harder to kill. 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