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Published on: May 19, 2020
Capsular polysaccharides of Acinetobacter baumannii modulate antimicrobial resistance and innate immune response
Laurita Klimkaite1, Giedre Kukanauskaite1, Joris Naujalis1
1Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, 10257, Lithuania.
Abstract:
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.
Insights
Capsular polysaccharides (CPS) in Acinetobacter baumannii are crucial for resisting antibiotics and host immune responses. Their absence increases susceptibility to some drugs but enhances biofilm resistance to others.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Acinetobacter baumannii is a multidrug-resistant opportunistic pathogen causing significant nosocomial infections.
- Understanding virulence factors like capsular polysaccharides (CPS) is critical for combating A. baumannii.
Purpose of the Study:
- To investigate the role of capsular polysaccharides (CPS) in antimicrobial resistance and host-pathogen interactions of Acinetobacter baumannii.
- To elucidate how CPS influences bacterial adaptation and immune evasion strategies.
Main Methods:
- Construction and analysis of a CPS-deficient mutant (∆galU) of A. baumannii.
- Assessment of antimicrobial susceptibility, biofilm formation, and resistance to various agents (antibiotics, disinfectants, photodynamic therapy).
- Gene expression analysis and evaluation of host immune responses (cytokine production, neutrophil chemotaxis, caspase-3 activation).
Main Results:
- CPS-deficient mutants showed increased susceptibility to gentamicin, tetracycline, colistin, and SDS.
- Absence of CPS led to enhanced biofilm formation with increased resistance to colistin, chlorhexidine, and hydrogen peroxide.
- CPS was essential for resistance to photodynamic therapy; purified CPS induced pro-inflammatory responses and neutrophil chemotaxis.
Conclusions:
- Capsular polysaccharides play a dual role in Acinetobacter baumannii, masking virulence factors and actively modulating host immune responses.
- CPS significantly impacts antimicrobial resistance, biofilm characteristics, and bacterial interaction with the host immune system.
- Targeting CPS could be a promising strategy to enhance antimicrobial efficacy and reduce A. baumannii pathogenicity.
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