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
429 [허원도 교수님] 한국과학기술한림원 2024년도 정회원 선출 생명과학과 2023.12.04 107
428 [유슬기(양한슬 교수님 연구실)] 제4회 'POSTECH SF 어워드', KAIST 유슬기 씨 당선 생명과학과 2024.02.27 133
427 [허원도 교수님] RNA 유전자 가위 정밀제어기술로 유전자 치료 성큼​ 생명과학과 2024.02.14 151
426 [정인경 교수님] 인공지능 기반 대장암 3차원 게놈 지도 최초 해독​ 생명과학과 2023.07.25 179
425 [허원도 교수님] 기억하고 인지하는 과정을 실시간 관찰하다 생명과학과 2024.01.10 191
424 [강석조 교수님] DNA 인식 선천면역인자의 방호패치 발견​ 생명과학과 2023.12.05 200
423 [김학성 교수님] 알츠하이머 조기 진단하는 센서단백질 디자인하다​ 생명과학과 2023.12.08 201
422 [김학성 명예교수님] 2023 효소공학상(Enzyme Engineering Award) 수상​ 생명과학과 2023.08.24 225
421 [김윤기, 조원기 교수님] 비정상 단백질 처리에 관여하는 새로운 인자 발견 생명과학과 2023.10.12 242
420 [강석조 교수님] 이행 호염구, 알레르기 매개 세포에 대한 새로운 이해 생명과학과 2023.11.08 245
419 [전상용 교수님] 탄수화물 나노입자로 염증성 장 질환 치료하다​ 생명과학과 2023.08.02 261
418 [김상규 교수님] 생명과학과의 낭만과학자 Eco Lab 대표 김사부(KAIST 유튜브) 생명과학과 2023.12.12 264
417 [이승재 교수님] 생체 에너지 발전소 부산물로 병원균 감염 제어​ 생명과학과 2023.07.11 271
416 [김윤기 교수님] 저용량 고효율 RNA백신 개발 가능해지다​ 생명과학과 2023.10.24 271
415 [김찬혁 교수님] 6월 ‘이달의 과학기술인상’ 수상 생명과학과 2023.06.08 272
414 [김재경 교수님] 포스코 사이언스 펠로십 선정​ 생명과학과 2023.10.18 275
413 [정원석 교수님] 아동 학대로 인한 정신질환 발병 원인 최초 규명​ 생명과학과 2023.08.01 282
412 [조병관 교수님 연구실] 2022년 안전관리 우수연구실 선정 file 생명과학과 2023.01.27 287
411 [정인경 교수님] 기저 질환이 없는 코로나19 환자의 중증 신규 유전적 위험 인자 규명 생명과학과 2022.09.29 334
410 [강창원, 서연수 교수님, 팔린다 박사님] 논문 Nucleic Acids Research 게재 생명과학과 2023.02.17 334
Board Pagination Prev 1 2 3 4 5 6 7 8 9 10 ... 22 Next
/ 22