Bacterial Stringent Signal Directs Virulence and Survival in Vibrio cholerae.

• 발행기관: 한국자원식물학회
• 저자명: Young Taek Oh Hwa Young Kim Sang Sun Yoon
• 간행물 정보: 『한국자원식물학회 학술심포지엄』2019년도 추계학술대회, 8~8쪽, 전체 1쪽
• 주제분류: 농수해양 > 기타농수해양
• 파일형태: PDF
• 발행일자: 2019.10.31

영문 초록

The stringent response (SR) is characterized as a bacterial defense mechanism in response to various growth-inhibiting stresses. It is activated by accumulation of a small nucleotide regulator, (p)ppGpp, and induces global changes in bacterial transcription and translation. Recent work from our group has shown that (p)ppGpp plays a critical role in virulence and survival in Vibrio cholerae. The genes, relA and relV, are involved in the production of (p)ppGpp, while the spoT gene encodes an enzyme that hydrolyzes it in V. cholerae. A mutant strain defective in (p)ppGpp production (i.e. ΔrelAΔrelVΔspoT mutant) lost the ability to produce cholera toxin (CT) and lost their viability due to uncontrolled production of organic acids, when grown with extra glucose. In contrast, the ΔrelAΔspoT mutant, a (p)ppGpp overproducer strain, produced enhanced level of CT and exhibited better growth in glucose supplemented media via glucose metabolic switch from organic fermentation to acetoin, a neutral fermentation end product, fermentation. These findings indicates that (p)ppGpp, in addition to its well-known role as a SR mediator, positively regulates CT production and maintenance of growth fitness in V. cholerae. This implicates SR as a promising drug target, inhibition of which may possibly downregulate V. cholerae virulence and survival fitness. Therefore, we screened a chemical library and identified a compound that induces medium acidification (termed iMAC) and thereby loss of wild type V. cholerae viability under glucose-rich conditions. Further, we present a potential mechanism by which the compound inhibits (p)ppGpp accumulation. Together, these results indicate that iMAC treatment causes V. cholerae cells to produce significantly less (p)ppGpp, an important regulator of the bacterial virulence and survival response, and further suggesting that it has a therapeutic potential to be developed as a novel antibacterial agent against cholera.