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
370 세계의 벽 사뿐히 넘을 잠재력 가득 가능성 무한대… 미래 한국의 대들보 과사무실 2006.10.23 12543
369 [한국경제] STRONG KOREA-한국인 과학자가 뛴다...생명과학 과사무실 2006.11.13 17090
368 [한국경제] 한국인 생명과학자가 최근 발표한 주요 연구 과사무실 2006.11.13 17263
367 정종경 교수 이달의 과학기술자상 12월 수상자로 선정 과사무실 2006.12.11 12329
366 [동아일보] 위암 당뇨 ‘맞춤 치료’ 길 열린다…SNP 지도 첫 완성 과사무실 2006.12.14 13357
365 박태관 교수 Bioconjugate Chemistry 편집위원 선임 과사무실 2007.01.02 12048
364 개교 36주년 기념 우수교원 포상 과사무실 2007.02.15 9985
363 고규영 교수님 Circulation Research 논문 COVER게재 과사무실 2007.03.21 13383
362 자연과학대학 우수 강의 교원 및 우수 직원 포상 과사무실 2007.03.29 10622
361 [연합뉴스]신종 박테리아 5개중 1개꼴 한국과학자 발견...이성택교수 과사무실 2007.04.04 15006
360 김진우 교수 경력개발상 수상 과사무실 2007.04.10 14714
359 서연수교수 도약연구지원사업 선정 과사무실 2007.04.23 12595
358 [조선일보] AMPK유전자, 암세포 치료에도 이용...정종경 교수팀 과사무실 2007.05.08 11988
357 초파리의 일주기 리듬에 관여하는 새로운 유전자 발견... 최준호 교수 연구팀 과사무실 2007.07.20 12909
356 2007년 국가지정 연구실 선정.. 최길주 교수 연구실 과사무실 2007.07.20 12641
355 생명과학과 출신 곽유상 박사 ... 美 대학교수 됐다 과사무실 2007.07.31 14020
354 김학성교수...독일화학誌에 발표 과사무실 2007.08.01 11998
353 생명과학과 권창섭 연구교수... Trends in Genetics지 논문 게재 과사무실 2007.08.20 13309
352 [조선일보] 생명과학과 김정회교수팀...자일리톨 추출 신기술 개발 과사무실 2007.08.29 13989
351 [대덕넷] 생명과학과 정종경교수... 과기부 2분기 우수과학자 10인 선정 과사무실 2007.09.04 13651
Board Pagination Prev 1 2 3 4 5 6 7 8 9 10 ... 22 Next
/ 22