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
410 송민섭 박사 Agarwal Award (2004) 수상 과사무실 2004.11.08 12670
409 [한겨레] BK21 중간평가: 최우수사업단으로 선정 과사무실 2004.12.09 11352
408 [서울경제] 생물분야: KAIST 생물사업단 선정 과사무실 2004.12.09 13999
407 [교육부] BK21사업 제2회 중간평가 결과 발표 과사무실 2004.12.09 12419
406 [동아일보] 김은준 교수 젊은 과학자상 수상 과사무실 2004.12.27 11931
405 이상열 교수(박사 85) KAIST 올해의 동문 선정 과사무실 2005.01.04 15169
404 최유라 학생 21세기 이끌 우수인재상 수상 과사무실 2005.01.27 11185
403 [조선일보] 김재섭 교수 고열에도 뇌손상 막는 유전자 최초 발견 과사무실 2005.01.31 12034
402 김재섭 교수 논문 Nature Genetics 게재 과사무실 2005.01.31 13507
401 임대식 교수 외 3명 개교 34주년 기념 우수교원 포상 과사무실 2005.02.15 10868
400 배기현 학생 창의활동상 수상 과사무실 2005.02.17 11239
399 남성훈 학생 외 2명 Bioneer Award (2004) 수상 과사무실 2005.02.22 12971
398 [매일경제] 김학성 오은규 연구팀 나노입자 특성 이용해 단백질 상호작용 분석 과사무실 2005.03.21 10900
397 임대식 교수 국가지정연구실사업 신규과제 선정 과사무실 2005.03.30 11447
396 [매일경제] 관절염 맞춤치료 길 열린다 - 강창원 교수·한양대 의대 배상철교수 공동연구팀 과사무실 2005.03.30 11897
395 [대덕넷] 제넥셀, 日 신약개발업체서 외자유치 과사무실 2005.03.31 10922
394 노운 세미나실 OPEN 기념식 과사무실 2005.05.18 12228
393 KAIST 김태국 교수 신약개발 사이언스지 발표 과사무실 2005.07.01 14256
392 이상기 박사 한국생명공학연구원장 취임 과사무실 2005.07.12 13553
391 [중앙일보] 김재섭 교수 치매 막는 신물질 4종 발견 과사무실 2005.08.08 12051
Board Pagination Prev 1 2 3 4 5 6 7 8 9 10 ... 22 Next
/ 22