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<p>Infections caused by multidrug-resistant <i>Acinetobacter baumannii</i> are an emerging global health threat. Although phages have shown promising results in treating bacterial infections, the mechanisms of the combined effect of phages and innate immunity on clearing <i>A. baumannii</i> remain unclear. Here, we report a synergistic effect of the complement system and phages on clearing multidrug-resistant <i>A. baumannii</i>. We show that <i>A. baumannii</i> rapidly adapts and becomes resistant to phage or serum complement by modifying the expression of capsule and lipooligosaccharides, which can be regulated through reversible transposon mutagenesis in the K locus. Compared to the encapsulated phenotype, the non-encapsulated, phage-resistant <i>A. baumannii</i> showed a higher level of membrane attack complex deposition and were susceptible to killing by complement. In contrast, the encapsulated phenotype escaped the complement system by shedding the membrane attack complex to the environment. Thus, while the complement system targets the non-encapsulated phenotype, the phage infects and eliminates the encapsulated subpopulation. These results suggest means of combatting antibiotic-resistant <i>A. baumannii</i> by a simultaneous treatment with phages and complement, a combination which can be supplemented further with antibacterial antibodies.</p> Graphical abstract <p></p>

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Antibiotic-resistant Acinetobacter baumannii can be killed by a combination of bacteriophages and complement

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月2日

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  • Carmen Chen,
  • Eva Krzyżewska-Dudek,
  • Sheetal Patpatia,
  • Vinaya Dulipati,
  • Sarah Natalia Mapelli,
  • Aycan Meral,
  • Juha Kotimaa,
  • Saija Kiljunen,
  • Seppo Meri

摘要

Infections caused by multidrug-resistant Acinetobacter baumannii are an emerging global health threat. Although phages have shown promising results in treating bacterial infections, the mechanisms of the combined effect of phages and innate immunity on clearing A. baumannii remain unclear. Here, we report a synergistic effect of the complement system and phages on clearing multidrug-resistant A. baumannii. We show that A. baumannii rapidly adapts and becomes resistant to phage or serum complement by modifying the expression of capsule and lipooligosaccharides, which can be regulated through reversible transposon mutagenesis in the K locus. Compared to the encapsulated phenotype, the non-encapsulated, phage-resistant A. baumannii showed a higher level of membrane attack complex deposition and were susceptible to killing by complement. In contrast, the encapsulated phenotype escaped the complement system by shedding the membrane attack complex to the environment. Thus, while the complement system targets the non-encapsulated phenotype, the phage infects and eliminates the encapsulated subpopulation. These results suggest means of combatting antibiotic-resistant A. baumannii by a simultaneous treatment with phages and complement, a combination which can be supplemented further with antibacterial antibodies.

Graphical abstract