North颅eastern Uni颅ver颅sity researchers have found that the bac颅terium that causes Lyme dis颅ease forms dor颅mant per颅sister cells, which are known to evade antibi颅otics. This sig颅nif颅i颅cant finding, they said, could help explain why it??s so dif颅fi颅cult to treat the infec颅tion in some patients. ??It hasn??t been entirely clear why it??s dif颅fi颅cult to treat the pathogen with antibi颅otics since there has been no resis颅tance reported for the causative agent of the dis颅ease,?? explained Uni颅ver颅sity Dis颅tin颅guished Pro颅fessor Kim Lewis, who led the North颅eastern research team. In other chronic infec颅tions, Lewis?? lab has tracked the resis颅tance to antibi颅otic therapy to the pres颅ence of per颅sister cells??which are drug-????tolerant, dor颅mant vari颅ants of reg颅ular cells. These per颅sister cells are exactly what they??ve iden颅ti颅fied here in Bor颅relia burgdor颅feri, the bac颅terium that causes Lyme?disease. The researchers have also reported two approaches??one of them quite promising??to erad颅i颅cate Lyme dis颅ease, as well as poten颅tially other nasty infections. Lewis and his col颅leagues pre颅sented their find颅ings in a paper pub颅lished online last week in the journal Antimi颅cro颅bial Agents and Chemotherapy. He co-????authored the paper with North颅eastern doc颅toral stu颅dents Bijaya Sharma and Autumn Brown, both PhD??16; recent grad颅uate Nicole Matluck, S??15, who received her Bach颅elor of Sci颅ence in Behav颅ioral Neu颅ro颅science; and Linden T. Hu, a pro颅fessor of mol颅e颅c颅ular biology and micro颅bi颅ology at Tufts University. The research was sup颅ported by grants from the Lyme Research Alliance and the National Insti颅tutes of?Health. Lyme dis颅ease affects 300,000 people annu颅ally in the U.S., according to the Cen颅ters for Dis颅ease Con颅trol and Pre颅ven颅tion, and is trans颅mitted to people via bites from infected black颅legged ticks. If caught early, patients treated with antibi颅otics usu颅ally recover quickly. How颅ever, about 10 to 20 per颅cent of patients, par颅tic颅u颅larly those diag颅nosed later, who have received antibi颅otic treat颅ment may have per颅sis颅tent and recur颅ring symp颅toms including arthritis, muscle pain, fatigue, and neu颅ro颅log颅ical prob颅lems. These patients are diag颅nosed with Post-????treatment Lyme Dis颅ease Syndrome. In addi颅tion to iden颅ti颅fying the pres颅ence of these per颅sister cells, Lewis?? team also pre颅sented two methods for wiping out the infection??both of which were suc颅cessful in lab tests. One involved an anti-????cancer agent called Mit颅o颅mycin C, which com颅pletely erad颅i颅cated all cul颅tures of the bac颅terium in one fell swoop. How颅ever, Lewis stressed that, given Mit颅o颅mycin C??s tox颅i颅city, it isn??t a rec颅om颅mended option for treating Lyme dis颅ease, though his team??s find颅ings are useful to helping to better under颅stand the?disease. ''The second approach, which Lewis noted is much more prac颅tical, involved pulse-????dosing an antibi颅otic to elim颅i颅nate per颅sis颅ters. The researchers intro颅duced the antibi颅otic a first time, which killed the growing cells but not the dor颅mant per颅sis颅ters. But once the antibi颅otic washed away, the per颅sis颅ters woke up, and before they had time to restore their pop颅u颅la颅tion the researchers hit them with the antibi颅otic again. Four rounds of antibi颅otic treat颅ments com颅pletely erad颅i颅cated the per颅sis颅ters in a test?tube. ??This is the first time, we think, that pulse-????dosing has been pub颅lished as a method for erad颅i颅cating the pop颅u颅la颅tion of a pathogen with antibi颅otics that don??t kill dor颅mant cells,?? Lewis said. ??The trick to doing this is to allow the dor颅mant cells to wake?up.?? He added: ??This gives you an idea that you could, in prin颅ciple, estab颅lish a sim颅ilar reg颅i颅ment for treating patients for this and other chronic diseases.?? Lewis is a fac颅ulty member in the biology depart颅ment and directs Northeastern??s Antimi颅cro颅bial Dis颅covery Center. Over the past decade he has led pio颅neering work on this spe颅cial颅ized class of cells pro颅duced by all pathogens known as per颅sis颅ters. Ear颅lier this year, Lewis, biology pro颅fessor Slava Epstein, and other col颅leagues pub颅lished ground颅breaking researchin Nature pre颅senting a new antibi颅otic that kills pathogens without encoun颅tering any detectable resistance. In pre颅vious work, Lewis?? lab iden颅ti颅fied a com颅pound called ADEP that causes dor颅mant per颅sister cells in MRSA to self-????destruct. This com颅pound was among the first options the researchers tried out to combat Lyme dis颅ease. But it didn??t work, and nei颅ther did com颅bi颅na颅tions of stan颅dard antibi颅otics used to treat the dis颅ease. The team thought it had hit a dead end yet remained vig颅i颅lant in its quest to iden颅tify promising alter颅na颅tive?options. ??What we came up with was the pulse-????dosing reg颅imen, which worked beau颅ti颅fully,?? Lewis explained. ??I think this could be very useful, espe颅cially for antibi颅otics for which resis颅tance doesn??t rapidly?develop.?? ''Though the researchers iden颅ti颅fied the pres颅ence of these per颅sister cells, they also note in their paper that the mech颅a颅nisms by which the per颅sis颅ters are able to sur颅vive remain unknown. More work in this area will be required, they?wrote. This is a press release that originally appeared on the Northwestern website. |
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