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Anti-virulence potential of iclaprim, a novel folic acid synthesis inhibitor, against Staphylococcus aureus.
Hao, Lingyun; Zhou, Jingwen; Yang, Han; He, Chunyan; Shu, Wen; Song, Haoyue; Liu, Qingzhong.
Afiliación
  • Hao L; Department of Clinical Laboratory, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Zhou J; Department of Clinical Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Zhijiang Middle Rd., Shanghai, 200071, China.
  • Yang H; Department of Clinical Laboratory, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • He C; Department of Clinical Laboratory, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Shu W; Department of Clinical Laboratory, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Song H; Department of Clinical Laboratory, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Liu Q; Department of Clinical Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Zhijiang Middle Rd., Shanghai, 200071, China. jiaodamedicine@foxmail.com.
Appl Microbiol Biotechnol ; 108(1): 432, 2024 Aug 05.
Article en En | MEDLINE | ID: mdl-39102054
ABSTRACT
Infections caused by Staphylococcus aureus pose a significant global public problem. Therefore, new antibiotics and therapeutic strategies are needed to combat this pathogen. This investigation delves into the effects of iclaprim, a newly discovered inhibitor of folic acid synthesis, on S. aureus virulence. The phenotypic and genotypic effects of iclaprim were thoroughly examined in relation to virulence factors, biofilm formation, and dispersal, as well as partial virulence-encoding genes associated with exoproteins, adherence, and regulation in S. aureus MW2, N315, and ATCC 25923. Then, the in vivo effectiveness of iclaprim on S. aureus pathogenicity was explored by a Galleria mellonella larvae infection model. The use of iclaprim at sub-inhibitory concentrations (sub-MICs) resulted in a reduction of α-hemolysin (Hla) production and a differential effect on the activity of coagulase in S. aureus strains. The results of biofilm formation and eradication assay showed that iclaprim was highly effective in depolymerizing the mature biofilm of S. aureus strains at concentrations of 1 MIC or greater, however, inhibited the biofilm-forming ability of only strains N315 and ATCC 25923 at sub-MICs. Interestingly, treatment of strains with sub-MICs of iclaprim resulted in significant stimulation or suppression of most virulence-encoding genes expression. Iclaprim did not affect the production of δ-hemolysin or staphylococcal protein A (SpA), nor did it impact the total activity of proteases, nucleases, and lipases. In vivo testing showed that sub-MICs of iclaprim significantly improves infected larvae survival. The present study offered valuable insights towards a better understating of the influence of iclaprim on different strains of S. aureus. The findings suggest that iclaprim may have potential as an anti-virulence and antibiofilm agent, thus potentially mitigating the pathogenicity of S. aureus and improving clinical outcomes associated with infections caused by this pathogen. KEY POINTS • Iclaprim effectively inhibits α-hemolysin production and biofilm formation in a strain-dependent manner and was an excellent depolymerizing agent of mature biofilm • Iclaprim affected the mRNA expression of virulence-encoding genes associated with exoproteins, adherence, and regulation • In vivo study in G. mellonella larvae challenged with S. aureus exhibited that iclaprim improves larvae survival.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Staphylococcus aureus / Pruebas de Sensibilidad Microbiana / Biopelículas / Factores de Virulencia / Larva / Antibacterianos Límite: Animals Idioma: En Revista: Appl Microbiol Biotechnol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Staphylococcus aureus / Pruebas de Sensibilidad Microbiana / Biopelículas / Factores de Virulencia / Larva / Antibacterianos Límite: Animals Idioma: En Revista: Appl Microbiol Biotechnol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania