Scholarlink

<p>Drug-resistance (DR) in bacteria often develops through the repetitive formation of drug-tolerant persisters, which survive antibiotics without genetic changes. It is unclear whether <i>Mycobacterium tuberculosis</i> (Mtb), the bacterium that causes tuberculosis (TB), undergoes a similar transitioning process. Recent studies highlight changes in trehalose metabolism as crucial for persister formation and drug resistance. Here, we observe that mutants lacking trehalose catalytic shift activity exhibited fewer DR mutants due to decreased persisters. This shift enhances Mtb survival during antibiotic treatment by increasing metabolic heterogeneity and drug tolerance, facilitating drug&#xa0;resistance. Rifampicin (RIF)-resistant bacilli display cross-resistance to other antibiotics linked to higher trehalose catalytic shift, explaining how multidrug resistance (MDR) can follow RIF-resistance. In particular, the HN878 W-Beijing strain exhibits higher trehalose catalytic shift, increasing MDR risk. Both genetic and pharmacological inactivation of this shift reduces persister formation and MDR development, suggesting trehalose catalytic shift as a potential therapeutic target to combat TB resistance.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Trehalose catalytic shift inherently enhances phenotypic heterogeneity and multidrug resistance in Mycobacterium tuberculosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月11日

查看全文
  • Jae Jin Lee,
  • Daniel H. Swanson,
  • Sun-Kyung Lee,
  • Stephanie Dihardjo,
  • Gi Yong Lee,
  • Sree Gelle,
  • Hoon Je Seong,
  • Emily R. M. Bravo,
  • Zachary E. Taylor,
  • Michael S. Van Nieuwenhze,
  • Abhyudai Singh,
  • Jong-Seok Lee,
  • Seokyong Eum,
  • SangNae Cho,
  • Benjamin M. Swarts,
  • Hyungjin Eoh

摘要

Drug-resistance (DR) in bacteria often develops through the repetitive formation of drug-tolerant persisters, which survive antibiotics without genetic changes. It is unclear whether Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), undergoes a similar transitioning process. Recent studies highlight changes in trehalose metabolism as crucial for persister formation and drug resistance. Here, we observe that mutants lacking trehalose catalytic shift activity exhibited fewer DR mutants due to decreased persisters. This shift enhances Mtb survival during antibiotic treatment by increasing metabolic heterogeneity and drug tolerance, facilitating drug resistance. Rifampicin (RIF)-resistant bacilli display cross-resistance to other antibiotics linked to higher trehalose catalytic shift, explaining how multidrug resistance (MDR) can follow RIF-resistance. In particular, the HN878 W-Beijing strain exhibits higher trehalose catalytic shift, increasing MDR risk. Both genetic and pharmacological inactivation of this shift reduces persister formation and MDR development, suggesting trehalose catalytic shift as a potential therapeutic target to combat TB resistance.