Scholarlink

<p><i>Acinetobacter</i><i> baumannii</i> is a critical priority pathogen due to its capacity to develop resistance to last-resort antibiotics and to form persistent biofilms. Both contribute to treatment failure. This study investigated co-regulatory mechanisms of ciprofloxacin resistance and biofilm formation in <i>A. baumannii</i> ATCC 19606. Stepwise antibiotic exposure yielded a ciprofloxacin-resistant isogenic strain (CipR), with a minimum inhibitory concentration (MIC) of 128&#xa0;µg/mL. CipR exhibited significantly enhanced biofilm formation compared to the susceptible strain (<i>P</i> ≤ 0.0001), with a strong positive correlation (Rs = 0.9818) between MIC values and biofilm biomass. Minimum biofilm eradication concentrations (MBEC) increased markedly in the CipR strain. Whole-genome sequencing identified CipR-mutations in <i>gyrB</i> (DNA gyrase subunit B), a multidrug efflux transporter, and a hypothetical protein. Transcriptomic analyses revealed overexpression of the quorum sensing (QS) system AbaI/AbaR in CipR biofilm cells. Inhibition of QS with sub-inhibitory streptomycin concentrations reduced biofilm formation without altering ciprofloxacin MIC, suggesting the existence of other co-regulatory pathways. Efflux pump inhibition with CCCP did not impact either biofilm biomass or resistance levels. Ciprofloxacin resistance acquisition incurred a metabolic cost, evidenced by XTT assays and reduced bacterial growth. Resistance downregulated the expression of adhesion-related genes and diminished functional adhesion/invasion of human lung epithelial cells. Overall, the findings suggest that ciprofloxacin resistance, biofilm formation, and virulence may be co-regulated in <i>A. baumannii</i>, possibly through QS and other yet-to-be-identified regulatory networks. These results provide novel insights into the adaptive mechanisms of <i>A. baumannii</i> and highlight potential targets for therapeutic intervention.</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

Ciprofloxacin resistance enhances biofilm formation and modulates virulence in Acinetobacter baumannii: Insights into the role of efflux pumps and quorum sensing

  • 期刊论文

  • 发表日期：

    2026年1月16日

查看全文
  • Sérgio G. Mendes,
  • Sofia I. Combo,
  • Thibault Allain,
  • Inês Mó,
  • Sara Domingues,
  • Andre G. Buret,
  • Gabriela J. Da Silva

摘要

Acinetobacter baumannii is a critical priority pathogen due to its capacity to develop resistance to last-resort antibiotics and to form persistent biofilms. Both contribute to treatment failure. This study investigated co-regulatory mechanisms of ciprofloxacin resistance and biofilm formation in A. baumannii ATCC 19606. Stepwise antibiotic exposure yielded a ciprofloxacin-resistant isogenic strain (CipR), with a minimum inhibitory concentration (MIC) of 128 µg/mL. CipR exhibited significantly enhanced biofilm formation compared to the susceptible strain (P ≤ 0.0001), with a strong positive correlation (Rs = 0.9818) between MIC values and biofilm biomass. Minimum biofilm eradication concentrations (MBEC) increased markedly in the CipR strain. Whole-genome sequencing identified CipR-mutations in gyrB (DNA gyrase subunit B), a multidrug efflux transporter, and a hypothetical protein. Transcriptomic analyses revealed overexpression of the quorum sensing (QS) system AbaI/AbaR in CipR biofilm cells. Inhibition of QS with sub-inhibitory streptomycin concentrations reduced biofilm formation without altering ciprofloxacin MIC, suggesting the existence of other co-regulatory pathways. Efflux pump inhibition with CCCP did not impact either biofilm biomass or resistance levels. Ciprofloxacin resistance acquisition incurred a metabolic cost, evidenced by XTT assays and reduced bacterial growth. Resistance downregulated the expression of adhesion-related genes and diminished functional adhesion/invasion of human lung epithelial cells. Overall, the findings suggest that ciprofloxacin resistance, biofilm formation, and virulence may be co-regulated in A. baumannii, possibly through QS and other yet-to-be-identified regulatory networks. These results provide novel insights into the adaptive mechanisms of A. baumannii and highlight potential targets for therapeutic intervention.