Antibacterial effects of BB-Cl-Amidine against multidrug-resistant Gram-positive pathogens via membrane disruption

  • J Antibiot (Tokyo). 2025 Oct 9. doi: 10.1038/s41429-025-00869-w.
Zhenfeng Wang  #  1  2 ,  Junhua Ma  #  2 ,  Jintuan Lin  #  2 ,  Congcong Li  #  2  3 ,  Yong Xiang  4 ,  Zhijian Yu  2 ,  Bing Bai  5 ,  Guiqiu Li  6  7 ,  Ying Wei  8  9
Affiliations
  • 1. Clinical Medical College, Jiamusi University, Jiamusi, Heilongjiang, China.
  • 2. Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, Shenzhen Nanshan People's Hospital, Shenzhen, China.
  • 3. School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen, China.
  • 4. Marketing Department ofGuangzhou branch ofVarian Medical Equipment Trading (Beijing) Corp, Guangzhou, China.
  • 5. Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, Shenzhen Nanshan People's Hospital, Shenzhen, China. [email protected].
  • 6. Clinical Medical College, Jiamusi University, Jiamusi, Heilongjiang, China. [email protected].
  • 7. Laboratory Medicine Center, Nanshan People's Hospital, Shenzhen, China. [email protected].
  • 8. Clinical Medical College, Jiamusi University, Jiamusi, Heilongjiang, China. [email protected].
  • 9. Heilongjiang Provincial Hospital, Harbin, Heilongjiang, China. [email protected].
  • # Contributed equally.
PMID: 41068498 DOI: 10.1038/s41429-025-00869-w
Abstract

The escalating prevalence of multidrug-resistant (MDR) gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and linezolid-resistant Enterococcus faecalis, highlights the critical demand for new Antibacterial agents that target resistance pathways. BB-Cl-Amidine is originally considered as a peptidyl arginine deiminase inhibitor and till now, its potential antimicrobial activity has not been explored. This study sought to evaluate the Antibacterial effectiveness and underlying mechanisms of BB-Cl-Amidine against MDR gram-positive pathogens. The results showed that BB-Cl-Amidine exhibited potent Antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 25 μM to 50 μM against MRSA, E. faecalis and various of Gram-positive bacteria clinical isolates. At sub-MIC concentrations, BB-Cl-Amidine significantly reduced biofilm formation in both S. aureus and E. faecalis. Moreover, the increased permeability and depolarizing membrane potential of S. aureus was found by BB-Cl-Amidine. The Antibacterial activity of BB-Cl-Amidine can be neutralized by cardiolipin (CL) and phosphatidylglycerol (PG). Furthermore, BB-Cl-Amidine exposure resulted in the abnormal expression of functional proteins correlated with the cell membranes and phospholipid metabolas. In summary, the potential Antibacterial and anti-biofilm activities of BB-Cl-Amidine are demonstrated via membrane disruption, offering a promising scaffold for combating MDR Gram-positive infections.

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