{"668102":{"#nid":"668102","#data":{"type":"news","title":"Scientists Discover Small RNA That Regulates Bacterial Infection","body":[{"value":"\u003Cdiv\u003E\u003Cp\u003EPeople with weakened immune systems are at constant risk of infection. \u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E, a common environmental bacterium, can colonize different body parts, such as the lungs, leading to persistent, chronic infections that can last a lifetime \u2013 a common occurrence in people with cystic fibrosis.\u003C\/p\u003E\u003Cp\u003EBut the bacteria can sometimes change their behavior and enter the bloodstream, causing chronic localized infections to become acute and potentially fatal. Despite decades of studying the transition in lab environments, how and why the switch happens in humans has remained unknown.\u003C\/p\u003E\u003Cp\u003EHowever, researchers at the Georgia Institute of Technology have identified the major mechanism behind the transition between chronic and acute \u003Cem\u003EP. aeruginosa\u003C\/em\u003E infections. \u003Ca href=\u0022https:\/\/biosciences.gatech.edu\/people\/marvin-whiteley\u0022\u003E\u003Cstrong\u003EMarvin Whiteley\u003C\/strong\u003E\u003C\/a\u003E \u2013 professor in the School of Biological Sciences and Bennie H. and Nelson D. Abell Chair in Molecular and Cellular Biology \u2013 and \u003Ca href=\u0022https:\/\/www.thewhiteleylab.com\/pengbo-cao.html\u0022\u003E\u003Cstrong\u003EPengbo Cao\u003C\/strong\u003E\u003C\/a\u003E, a postdoctoral researcher in Whiteley\u2019s lab, discovered a gene that drives the switch. By measuring bacterial gene expression in human tissue samples, the researchers identified a biomarker for the transition.\u003C\/p\u003E\u003Cp\u003ETheir research findings, \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41586-023-06111-7\u0022\u003E\u003Cstrong\u003Epublished in \u003C\/strong\u003E\u003Cem\u003E\u003Cstrong\u003ENature\u003C\/strong\u003E\u003C\/em\u003E\u003C\/a\u003E, can inform the development of future treatments for life-threatening acute infections.\u003C\/p\u003E\u003Cp\u003EAccording to Whiteley and Cao, bacteria, like animals, are versatile and behave differently depending on their environment. A person with a chronic infection might be fine one day, but environmental changes in the body can cause bacteria to change their behavior. This can lead to acute infection, and a person could develop sepsis that requires immediate treatment.\u003C\/p\u003E\u003Cp\u003E\u201cFor years, people have been studying these bacteria in well-controlled lab environments, even though the lab is a place most microbes have never seen,\u201d said Whiteley. \u201cOur study took a novel approach to look directly into the bacterium\u2019s behavior in the human host.\u201d\u003C\/p\u003E\u003Cp\u003EThe researchers chose to look at human tissue samples of chronic bacterial lung and wound infections. Using genetic sequencing technologies, Whiteley and Cao measured the levels of all types of mRNA present in the bacteria. The mRNAs encode the proteins that do all the work in a cell, so by measuring a bacterium\u2019s mRNA level, one can infer the bacterium\u2019s behavior.\u003C\/p\u003E\u003Cp\u003EWhile \u003Cem\u003EP. aeruginosa\u003C\/em\u003E has roughly 6,000 genes, Whiteley and Cao found that one gene in particular \u2013 known as PA1414 \u2013 was more highly expressed in human tissue samples than all the other thousands of genes combined. The levels were so high that, at first, Cao and Whiteley thought the amount of PA1414 mRNA might be an artifact \u2013 a glitch associated with the sequencing methods.\u003C\/p\u003E\u003Cp\u003E\u201cThis particular gene is not expressed in the standard lab environment very much, so it was striking to see these levels,\u201d Cao said. \u201cAnd at this point, the function of the gene was unknown.\u201d \u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe researchers also found that low oxygen drives the high expression of the gene. This is a common environmental characteristic of bacterial infections, as bacteria frequently encounter oxygen deprivation during chronic infections. Further tests showed that the gene also regulates bacterial respiration under low oxygen conditions.\u003C\/p\u003E\u003Cp\u003EInterestingly, the researchers found that rather than encoding a protein, the gene encodes a small RNA that plays a vital role in bacterial respiration. They named the small RNA SicX (sRNA inducer of chronic infection X).\u003C\/p\u003E\u003Cp\u003EThe researchers then tested the functions of the gene in different animal infection models. They observed that when SicX wasn\u2019t present, the bacteria easily disseminated from chronic infections throughout the body, causing systemic infection. The comparison allowed the researchers to determine that the gene is important for promoting chronic localized infection. Moreover, researchers also showed that the expression of SicX immediately decreased during the transition from chronic to acute infection, suggesting SicX potentially serves as a biomarker for the chronic-to-acute switch.\u003C\/p\u003E\u003Cp\u003E\u201cIn other words, without the small RNA, the bacteria become restless and go looking for oxygen, because they need to breathe like we need to breathe,\u201d Whiteley said. \u201cThat need causes the bacteria to enter the bloodstream. Now, we know that oxygen levels are regulating this transition.\u201d\u003C\/p\u003E\u003Cp\u003EHaving a better indication for when an infection might enter the bloodstream would be a paradigm shift for treatments.\u003C\/p\u003E\u003Cp\u003E\u201cIf you can predict when an acute infection will occur, a patient could take a diagnostic test at home to determine if and when they may need to get treatment \u2013 before the infection becomes life-threatening,\u201d Whiteley said. \u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe study provides answers to the long-standing questions about how and why chronic infections become acute. The researchers\u2019 findings also open opportunities to develop therapeutics that target this specific molecular behavior associated with \u003Cem\u003EP. aeruginosa\u003C\/em\u003E infections.\u003C\/p\u003E\u003Cp\u003E\u201cThe chronic \u003Cem\u003EPseudomonas \u003C\/em\u003Einfection is usually highly resistant to first-line antibiotics,\u201d Cao said. \u201cBy targeting this small RNA, we could potentially change the lifestyle of the bacteria to make it more susceptible to antibiotic treatments and achieve greater clearance of these dangerous infections.\u201d\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EMarvin Whiteley is also an Eminent Scholar with the \u003Ca href=\u0022https:\/\/gra.org\/\u0022\u003E\u003Cstrong\u003EGeorgia Research Alliance\u003C\/strong\u003E\u003C\/a\u003E.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECitation\u003C\/strong\u003E: Cao, P., Fleming, D., Moustafa, D.A.,\u0026nbsp;et al.\u0026nbsp;A\u0026nbsp;\u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E\u0026nbsp;small RNA regulates chronic and acute infection.\u0026nbsp;\u003Cem\u003ENature\u003C\/em\u003E\u0026nbsp;\u003Cstrong\u003E618\u003C\/strong\u003E, 358\u2013364 (2023).\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EDOI\u003C\/strong\u003E: \u003Ca href=\u0022https:\/\/doi.org\/10.1038\/s41586-023-06111-7\u0022\u003E\u003Cstrong\u003Ehttps:\/\/doi.org\/10.1038\/s41586-023-06111-7\u003C\/strong\u003E\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EFunding\u003C\/strong\u003E: NIH grants R21AI154220, R21AI137462, and R21AI147178; Cystic Fibrosis Foundation grants WHITEL20A0 and WHITEL22G0; Cystic Fibrosis Trust Foundation grant SRC017; and Cystic Fibrosis Postdoctoral Fellowships CAO20F0 and DOLAN20F0\u003C\/p\u003E\u003C\/div\u003E\u003Cp\u003E\u003Cbr\u003E\u0026nbsp;\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EResearchers at the Georgia Institute of Technology have identified the major mechanism behind the transition between chronic and acute\u0026nbsp;\u003Cem\u003EP. aeruginosa\u003C\/em\u003E\u0026nbsp;infections.\u0026nbsp;Their research findings can inform the development of future treatments for life-threatening acute infections.\u003C\/p\u003E\r\n","format":"limited_html"}],"field_summary_sentence":[{"value":"The researchers identified the major molecular mechanism behind the transition between chronic and acute P. aeruginosa infections."}],"uid":"36123","created_gmt":"2023-06-14 18:13:19","changed_gmt":"2024-09-24 19:11:31","author":"Catherine Barzler","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2023-06-14T00:00:00-04:00","iso_date":"2023-06-14T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"670978":{"id":"670978","type":"image","title":"Pseudomonas aeruginosa","body":"\u003Cp\u003EPseudomonas aeruginosa clumps grown in synthetic cystic fibrosis sputum.\u0026nbsp;\u003C\/p\u003E\r\n","created":"1686765943","gmt_created":"2023-06-14 18:05:43","changed":"1686766040","gmt_changed":"2023-06-14 18:07:20","alt":"An image of purple and green bacteria taken with a microscope","file":{"fid":"253954","name":"pseudomonas aeruginosa 2[87].png","image_path":"\/sites\/default\/files\/2023\/06\/14\/pseudomonas%20aeruginosa%202%5B87%5D.png","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2023\/06\/14\/pseudomonas%20aeruginosa%202%5B87%5D.png","mime":"image\/png","size":1091693,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2023\/06\/14\/pseudomonas%20aeruginosa%202%5B87%5D.png?itok=LSw7JGUE"}}},"media_ids":["670978"],"groups":[{"id":"1214","name":"News Room"},{"id":"1188","name":"Research Horizons"}],"categories":[],"keywords":[{"id":"192250","name":"cos-microbial"},{"id":"192003","name":"Center for Microbial Dynamics and Infection (CMDI)"},{"id":"188231","name":"CMDI"},{"id":"172754","name":"Marvin Whiteley"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"},{"id":"71881","name":"Science and Technology"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:catherine.barzler@gatech.edu\u0022\u003ECatherine Barzler,\u003C\/a\u003E Senior Research Writer\/Editor\u003C\/p\u003E","format":"limited_html"}],"email":["catherine.barzler@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}