[New Publication] IPK identified the potent antibacterial efficacy and new mechanism of action of oxythiamine

[New Publication] IPK identified the potent antibacterial efficacy
and a new mechanism of action of oxythiamine

Institut Pasteur Korea(IPK) identified the potent antibacterial efficacy and new mechanism of action of oxythiamine. Through this study, the oxythiamine, which has previously been known as an antimetabolite of vitamin B1, was found to effectively prohibit P. aeruginosa that is resistant to carbapenem, the most powerful antibiotic currently available, and increase the sensitivity of the resistant bacteria to antibiotics in cell culture and animal model experiments. 

Kim et al., 2022, Cell Chemical Biology 29, 1317–1324,

P. aeruginosa mainly causes inflammation in the lungs and respiratory tract and is one of the leading causes of hospital-required infections in domestic and overseas. Due to the resistance, however, it is difficult to treat with existing antibiotics.

The Antibacterial Resistance Lab. of IPK, led by Dr. Soojin Jang, searched for the compounds that effectively inhibit the growth of
P. aeruginosa among the 230,000 compounds library. Utilizing the IPK's image-based screening platform that can precisely observe and quantify complex phenomena of intracellular infection and treatment,  researchers identified potent candidates, including oxythiamine. In addition, in collaboration with a research team at Nanyang Technological University in Singapore, they verified the in vivo efficacy of oxythiamine in an animal model. 

Next, Dr. Jang's team elucidated the antibacterial mechanism of the candidate through multi-omics research including transcriptome, genome, and metabolite analysis. They explained that oxythiamine is bioactivated to oxythiamine-pyrophosphate(OTH-PP) and OTH-PP inhibits bacterial growth by perturbation of thiamine metabolism. The research team added that the inhibition of bacterial thiamine metabolism could increase the susceptibility of bacteria to various small molecules, including existing antibiotics, which provide insights into potent drug combination options. 

This research responds to the unmet global need for an immediate response to antibiotic resistance (AMR). The World Health Organization (WHO) has reported that at least 700,000 people die every year due to infection with resistant bacteria and it casts one of the greatest threats to mankind. The new candidate and its novel antibacterial mechanisms derived through research are expected to expedite the development of innovative therapeutics.

IPK has been taking various strategies to respond to AMR, including new drug development research and international cooperation. Centered in the Antibacterial Resistance Lab., IPK is developing new antibiotics for major resistant bacteria and has been analyzing the changes in antibiotic resistance due to COVID-19. In addition, participating in the MetaSUB global consortium in which 32 countries, including S. Korea, joined, researchers are investigating and analyzing the distribution of microbiome and antibiotic-resistant bacteria in urban environments. In particular, IPK is keen to activate a regional joint response to
 AMR by holding regular discussions with 10 research institutes located in 7 countries in the Asia-Pacific region of the Pasteur Network and is now preparing for an international symposium on October 7, following the one previously held in 2021. Indeed, in December 2021, a webinar on AMR was held jointly with the International Vaccine Research Institute, the Asian Development Bank, the Danish Embassy in Korea, and the International Center for Antibiotic Resistance Research.

Dr. Youngmee Jee, the IPK CEO, said, “The threats of AMR are growing quietly and consistently hidden behind the COVID-19 crisis, and our response to AMR should be quick and immediate.” “We will spur research on innovative antibiotic development leveraging our expertise, technology, and infrastructure in infectious disease and strive to exchange information and promote joint research through active cooperation.”

The research was carried out with the support of the Ministry of Science and ICT of Korea and the Ministry of Education of Singapore and published in the 'Cell Chemical Biology' Volume. 29 Issue. 8 on August 18, 2022.