{"667505":{"#nid":"667505","#data":{"type":"news","title":"Bacteria Can Discard Damage to Survive Antibiotic Treatment","body":[{"value":"\u003Cp\u003EIt\u2019s the quiet bacteria that you\u2019ve got to watch out for, the bacteria that can survive antibiotic treatments by forming dormant, drug-tolerant \u201cpersisters.\u201d These persister bacteria can wake up after treatment and prolong infections.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EPersisters were first described about 80 years ago in some of the first studies of the antibiotic penicillin. Later, it was discovered that these bacteria didn\u2019t have genetic resistance to antibiotics \u2013 they basically go dormant, hibernating, essentially hiding from the treatment that has been designed to kill them.\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EHow they wake up again has remained a mystery. But researchers with the\u0026nbsp;\u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/\u0022\u003EWallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University\u003C\/a\u003E\u0026nbsp;are working to solve it. Along the way they\u2019ve developed a better understanding of how bacteria can resist the therapeutic power of antibiotics, which could lead to more effective treatments down the road.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u201cThese persisters don\u2019t have the genes that can inactivate an antibiotic, but they still survive treatment,\u201d said\u0026nbsp;\u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/faculty\/Kyle-Allison\u0022\u003EKyle Allison\u003C\/a\u003E, whose lab\u0026nbsp;\u003Ca href=\u0022https:\/\/www.embopress.org\/doi\/full\/10.15252\/msb.202211320\u0022\u003Erecently published its work in the journal\u0026nbsp;\u003Cem\u003EMolecular Systems Biology\u003C\/em\u003E\u003C\/a\u003E. In fact, their study made the cover of the print edition published this month.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u201cPersisters are thought to play a role in a lot of different kinds of chronic infections,\u201d Allison said. \u201cWe approached them like an engineering problem. Rather than trying to invent or discover a brand-new antibiotic, perhaps all we need to do is understand why these bacteria survive.\u201d\u003C\/p\u003E\r\n\r\n\u003Cp\u003EMost studies of persisters focus on figuring out how they form. But Allison reasoned that the therapeutically interesting question is: How do they wake up or resuscitate from their dormant state?\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u201cIt\u2019s a challenge to study this because these are rare cells, and bacterial cells are very small, so they\u2019re hard to track and it\u2019s hard to monitor their behaviors,\u201d said Allison. \u201cSo, we developed methods that can look at thousands of cells at high magnification over long periods of time. That enabled us to study resuscitation \u2013 the waking-up moment for these persister cells in a statistically rigorous way.\u201d\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAllison \u2013 whose partner in the study was lead author Xin Fang, a postdoc in his lab \u2013 said they expected the bacterial cells to wake up randomly, which would be consistent with past studies into the phenomenon. But the activity of individual persister bacteria cells had never been verified. Through their close inspection, using single-cell time-lapse microscopy, Allison and Fang noticed that persisters wake up at an accelerated rate after antibiotic treatment.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u201cThis led to some interesting questions,\u201d Allison said. \u201cWas the antibiotic having an effect on the dormant persisters? They were thought to hibernate, to be oblivious to the antibiotic. But we saw that the antibiotic actually does have an effect \u2013 the more antibiotic they get during treatment, the slower they are to wake back up. We were even able to show that there is some damage in the persisters from the antibiotic treatment, and many persisters actually appear to discard that damage.\u201d\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBasically, it looked as if some persisters were actually sacrificing themselves, allowing the group to wake up and develop colonies. The persisters seemed to be enabling their own survival by partitioning \u2013 allowing some to die off so the rest can survive.\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAnd the researchers saw this behavior when they studied multiple, different pathogens (escherichia coli, salmonella enterica, pseudomonas aeruginosa, and klebsiella pneumoniae)\u0026nbsp;that cause completely different types of infection and have different mechanisms for tolerating antibiotics.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u201cThe fact that they all have this cellular partitioning when they wake up after antibiotic treatment was pretty surprising,\u201d Allison said. \u201cIt indicates the possibility that this non-genetic mechanism allows bacteria to survive in patients.\u201d\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAllison has been interested in the subject of antibiotic resistance since he was in graduate school. While he can\u2019t claim that this resuscitation phenomenon is widespread in patients, the fact that the researchers observed it happening in lab samples, and randomly chosen patient samples, \u201cis probably pretty significant,\u201d he said. \u201cIt hints strongly that this may be an important mechanism underlying treatment failure in bacteria that lack genetic resistance.\u201d\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe exploratory and unique nature of the research was made possible by an NIH Director\u2019s Early Independence Award, which grants flexibility to junior scientists like Allison pursuing high-risk research.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ECITATION: Xin Fang, Kyle Allison. \u201cResuscitation dynamics reveal persister partitioning after antibiotic treatment.\u201d\u0026nbsp;\u003Cem\u003EMolecular Systems Biology\u003C\/em\u003E, April 2023.\u0026nbsp;\u0026nbsp;\u003Ca href=\u0022https:\/\/doi.org\/10.15252\/msb.202211320\u0022\u003Edoi.org\/10.15252\/msb.202211320\u003C\/a\u003E\u003C\/p\u003E\r\n","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EDormant bacteria resuscitates in presence of antibiotic\u003C\/p\u003E\r\n","format":"limited_html"}],"field_summary_sentence":[{"value":"Dormant bacteria resuscitates in presence of antibiotic"}],"uid":"28153","created_gmt":"2023-04-24 21:02:50","changed_gmt":"2023-04-25 19:21:17","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2023-04-24T00:00:00-04:00","iso_date":"2023-04-24T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"670614":{"id":"670614","type":"image","title":"Karmella.jpg","body":"\u003Cp\u003EKarmella Haynes is exploring the dark matter of the genome.\u003C\/p\u003E\r\n","created":"1682369866","gmt_created":"2023-04-24 20:57:46","changed":"1693229676","gmt_changed":"2023-08-28 13:34:36","alt":"Karmella Haynes"}},"media_ids":["670614"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1188","name":"Research Horizons"}],"categories":[],"keywords":[{"id":"187915","name":"go-researchnews"},{"id":"187423","name":"go-bio"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003C\/p\u003E\r\n","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}