<p><i>Acinetobacter baumannii</i> is an opportunistic pathogen characterised by multidrug resistance and is among the leading causes of nosocomial infections. This study investigated the role of capsular polysaccharides (CPS) in antimicrobial resistance and host-pathogen interaction. CPS-deficient mutant (∆<i>galU</i>) displayed increased susceptibility to <?tk 3?>gentamicin, tetracycline, colistin, and sodium dodecyl sulfate (SDS). In the absence of CPS, bacteria adapted by forming biofilm, characterised by a thicker extracellular matrix. These biofilms displayed increased resistance to colistin, chlorhexidine, and hydrogen peroxide, but remained sensitive to tetracycline and SDS. CPS were also essential for the resistance to photodynamic therapy induced by blue light and chlorophyllin. Gene expression analysis revealed upregulation of <i>galU</i> gene under the exposure to antibiotics, blue light, fetal bovine serum, and during the contact with macrophages. CPS-deficient mutant and its derived outer <?tk 3?>membrane vesicles elicited a stronger pro-inflammatory response, compared to wild-type. CPS shielding <i>A. baumannii</i> demonstrated the ability to induce caspase-3 activation to a greater extent compared to the mutant strain. Moreover, purified CPS induced pro-inflammatory cytokine expression in sterile infection and promoted neutrophil chemotaxis. Altogether, this study demonstrates that CPS not only mask <i>A. baumannii</i> virulence surface structures, but also actively modulate host immune response and antimicrobial 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

Capsular polysaccharides of Acinetobacter baumannii modulate antimicrobial resistance and innate immune response

  • Laurita Klimkaite,
  • Giedre Kukanauskaite,
  • Joris Naujalis,
  • Danas Ivanauskas,
  • Dominykas Grigorjevas,
  • Greta Petrenaite,
  • Meda Skinkyte,
  • Jekaterina Porchun,
  • Egle Zalyte,
  • Irina Buchovec,
  • Jurate Skerniskyte

摘要

Acinetobacter baumannii is an opportunistic pathogen characterised by multidrug resistance and is among the leading causes of nosocomial infections. This study investigated the role of capsular polysaccharides (CPS) in antimicrobial resistance and host-pathogen interaction. CPS-deficient mutant (∆galU) displayed increased susceptibility to gentamicin, tetracycline, colistin, and sodium dodecyl sulfate (SDS). In the absence of CPS, bacteria adapted by forming biofilm, characterised by a thicker extracellular matrix. These biofilms displayed increased resistance to colistin, chlorhexidine, and hydrogen peroxide, but remained sensitive to tetracycline and SDS. CPS were also essential for the resistance to photodynamic therapy induced by blue light and chlorophyllin. Gene expression analysis revealed upregulation of galU gene under the exposure to antibiotics, blue light, fetal bovine serum, and during the contact with macrophages. CPS-deficient mutant and its derived outer membrane vesicles elicited a stronger pro-inflammatory response, compared to wild-type. CPS shielding A. baumannii demonstrated the ability to induce caspase-3 activation to a greater extent compared to the mutant strain. Moreover, purified CPS induced pro-inflammatory cytokine expression in sterile infection and promoted neutrophil chemotaxis. Altogether, this study demonstrates that CPS not only mask A. baumannii virulence surface structures, but also actively modulate host immune response and antimicrobial resistance.