The mechanism of vancomycin resistance in VISA and the role of reverse antibiotic (RA)

Keiichi Hiramatsu, Yuhu Morimoto, Tadashi Baba, Takashi Sasaki, Tomomi Hishinuma, Yuki Katayama, Miki Matsuo, Kyoko Kuwahara, Yuki Uehara, Masayuki Igarashi

Research output: Contribution to journalReview articlepeer-review


Anti-bacterial chemotherapy of the last century has greatly contributed to the welfare and prolongation human life by conquering the threat of bacterial infection. However, in 21st century, we started to notice the rise of antimicrobial resistance in the pathogenic bacteria causing infection refractory to chemotherapy. That trend suppressed the motivation of pharmaceutical companies to develop new antimicrobial agents. However, it is important to regard the resistance emergence is an inevitable result since resistance has been a phenomenon existent since much before the rise of humans on the earth. Given this, it is necessary for us to raise antimicrobials against antibiotic-resistant pathogens. We re-discovered a natural antibacterial substance called nybomycin by screening the soil bacterial culture, which exhibited potent antimicrobial activity against quinolone-resistant bacteria but poor activity against quinolone-susceptible bacteria. Although at a very low frequency, bacteria do produce nybomycin-resistant mutants. However, we found that the resistant mutants carried a reverse mutation in a codon of gyrA gene encoding DNA gyrase subunit A, which cured the bacteria of quinolone resistance. We designated nybomycin reverse antibiotic(RA). We expect that this discovery of new genre of antibiotic class in nature would lead to revitalization of chemotherapy.

Original languageEnglish
Pages (from-to)503-512
Number of pages10
JournalJapanese Journal of Chemotherapy
Issue number3
Publication statusPublished - 05-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)


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