KAIST 생명과학과동창회
  • News & Events
  • News

News

Antibiotic tolerance study paves way for new treatments

Posted on Mar 02, 2021, 3 p.m.


A new study identifies a mechanism that makes bacteria tolerant to penicillin and related antibiotics, findings that could lead to new therapies that boost the effectiveness of these treatments.


Antibiotic tolerance is the ability of bacteria to survive exposure to antibiotics, in contrast to antibiotic resistance, when bacteria actually grow in the presence of antibiotics. Tolerant bacteria can lead to infections that persist after treatment and may develop into resistance over time.


The study in mice, “A Multifaceted Cellular Damage Repair and Prevention Pathway Promotes High Level Tolerance to Beta-lactam Antibiotics,” published Feb. 3 in the journal EMBO Reports, reveals how tolerance occurs, thanks to a system that mitigates iron toxicity in bacteria that have been exposed to penicillin.


“We’re hoping we can design a drug or develop antibiotic adjuvants that would then basically kill off these tolerant cells,” said senior author Tobias Dörr, assistant professor of microbiology in the Weill Institute for Cell and Molecular Biology in the College of Agriculture and Life Sciences.


Co-authors included Ilana Brito, the Mong Family Sesquicentennial Faculty Scholar and assistant professor in the Meinig School of Biomedical Engineering in the College of Engineering, and Lars Westblade, associate professor of pathology and laboratory medicine at Weill Cornell Medicine.


Some bacteria, including the model bacterium used in the study, Vibrio cholerae, which causes cholera in humans, are remarkably tolerant to penicillin and related antibiotics, known as beta-lactam antibiotics. It has been known for a long time that beta-lactam antibiotics break down bacterial cell walls, but how bacteria survive loss of their cell walls was poorly understood.


In the study, the researchers developed a V. cholerae mutant that lacked a two-component damage repair response system that controls a gene network encoding diverse functions. Without the system, known as VxrAB, when the cell wall is damaged by antibiotics, the transfer of electrons across the cell membrane goes awry, leading to electrons ending up on the wrong molecules. This misdirection causes hydrogen peroxide to accumulate in the cell, which changes the oxidation state of cellular iron and disrupts signals for the cell to tell how much iron it has.  


In the presence of hydrogen peroxide, the mutant bacteria cannot sense how much iron has been acquired, and it behaves as if it is iron-starved and seeks to acquire more iron. Left unchecked, these circumstances cause iron toxicity, which will kill the cell, according to the experiments the researchers conducted. In further tests with mutant V. cholerae bacteria, both in test tubes and in mice, the researchers showed that reducing the influx of iron increased the bacteria’s tolerance to beta-lactams.


Fortunately for normal V. cholerae, exposure to antibiotics and the breakdown of the cell’s walls activate the VxrAB system, which works to repair cell walls and downregulates iron uptake systems, and thereby creates antibiotic tolerance. More study is needed to understand what triggers the VxrAB system in the presence of beta-lactam antibiotics.


The research opens the door for developing new drugs that could be combined with antibiotics to exploit oxidative damage and iron influx in tolerant bacteria. In future work, the researchers will search for parallel mechanisms of tolerance in other bacterial pathogens.


Jung-Ho Shin, a postdoctoral researcher in Dörr’s lab, is the paper’s first author. Co-authors include researchers from the Korea Advanced Institute of Science and Technology, the Korea Advanced Institute of Science and Technology, and the Intelligent Synthetic Biology Center in Korea.

The study was funded by the National Research Foundation of Korea and the National Institutes of Health.


https://www.worldhealth.net/news/antibiotic-tolerance-study-paves-way-new-treatments/


List of Articles
번호 제목 글쓴이 날짜 조회 수
95 전상용 교수, 94회 일본화학회 정기학회 'Distinguished Lectureship Award' 수상 과사무실 2014.04.02 13076
94 전상용 교수, ACS Nano 게재(2014.2) 과사무실 2014.03.12 12722
93 전상용 교수, Cancer Research게제(2014.2) 과사무실 2014.03.12 13151
92 전상용 교수, Theranostics 저널 최다 피인용 논문상 수상 / Professor Sangyong Jon receives The Most Cited Paper Award by the “Theranostics” Journal 과사무실 2015.04.21 12543
91 전상용 교수, 몸 속 물질 이용한 염증 치료제 개발 / Prof. Sang-Yong Jon developed anti-inflammatory drug using biological materials 생명과학과 2016.06.15 20057
90 전상용 교수, 암 치료를 위한 새로운 펩타이드-항체 복합체(하이브리드) 기술 개발 file 생명과학과 2019.02.21 6121
89 전상용 교수, 차세대 면역항암제 플랫폼 개발 위한 공동연구협약 체결 / Professor Sangyong Jon, make a research-cooperation contract for developing next-genreation anti-cancer drug platform 관리자 2016.01.08 16133
88 전상용 교수님_ 면역항암제 효율 높인 나노입자 백신 개발 file 생명과학과 2020.06.17 3269
87 전상용 교수님_Researchers review future directions of nanomedicine development 생명과학과 2020.12.28 1029
86 전상용, 송지준 교수님_다양한 변이에도 면역 가능한 인플루엔자 백신 개발 생명과학과 2021.06.30 760
85 전상용,이대엽 임성갑 교수, 암 줄기세포 제작 원천기술 개발 file 생명과학과 2018.11.30 6764
84 전상용교수님_항암제 표적 단백질을 약물 전달체로 쓴다?​ file 생명과학과 2020.08.26 2959
83 정원석 교수_ 삼성전자, ‘세계 알츠하이머의 날’ 맞아 연구원 노력 담은 영상 공개 생명과학과 2020.09.21 2647
82 정원석 교수님_Astrocytes eat connections to maintain plasticity in adult brains 생명과학과 2020.12.28 1816
81 정원석 교수님_KAIST, 신경세포의 흥분성 증가로 인한 뇌 질환 기제 규명 생명과학과 2021.06.03 1405
80 정원석 교수님_국내 연구진, 우리 뇌가 계속 일할 수 있는 이유 밝혀 생명과학과 2021.02.26 1659
79 정유진 석사과정 학생, 조병관 교수 Nature Communications 논문 게재(2016.06) / Yujin Jeong, a Master's degree student and Prof. Byung-Kwan Cho published a paper in Nature Communications (2016.06) 생명과학과 2016.06.07 14279
78 정인경 교수, 인체 조직읜 3차원 게놈지도 해독 file 생명과학과 2019.09.25 4614
77 정인경 교수님_KAIST, 전 세계 최대 규모의 3차원 암 게놈 지도 구축 생명과학과 2020.12.29 1296
76 정인경 교수님_유전자 온-오프 스위치 비밀 밝히는 정인경 카이스트 교수 생명과학과 2021.07.26 1148
Board Pagination Prev 1 ... 13 14 15 16 17 18 19 20 21 22 Next
/ 22