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Updated: May 22, 2026

Separating Bacteria by Capsule Amount Using a Discontinuous Density Gradient
Published on: January 7, 2019
Capsule modulation enhances immunity and delays resistance in MDR Acinetobacter baumannii
Fangfang Shen1,2, Yuanfei Wang3, Qiong Wu1,4
1Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230027, China.
Abstract:
Multidrug-resistant Acinetobacter baumannii (MDRAB) is a serious clinical threat. Although bacteriophages provide pathogen-specific therapy, the rapid emergence of phage resistance limits clinical durability. Here, we isolated a lytic phage, WYF231108.1, from hospital wastewater targeting the clinical isolate AHMU_SF230901.1 (SF). Through serial passage, we generated phage-resistant derivatives (SF_R1, SF_R2, SF_R3) and host-range-adapted phages (WYF_V1, WYF_V2, WYF_V3). Genomic and phenotypic profiling showed that resistance coincided with capsule attenuation and downregulation of capsule-biosynthesis genes, accompanied by reduced virulence and enhanced recognition by innate immune cells. Adapted phages restored lytic activity against resistant strains and, when combined with antibiotics, suppressed resistant outgrowth in vitro and improved survival in murine infection models. Collectively, our results define an evolutionary trade-off in which phage resistance associated with capsule attenuation reduces pathogenicity while exposing a therapeutic vulnerability. This vulnerability may be exploited using an adapted phage-antibiotic combination regimen.
Insights
Bacteriophage resistance in multidrug-resistant Acinetobacter baumannii (MDRAB) leads to capsule loss, reducing virulence. Adapted phages combined with antibiotics effectively treat MDRAB infections, overcoming resistance.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacteriophage Therapy
Background:
- Multidrug-resistant Acinetobacter baumannii (MDRAB) poses a significant clinical challenge.
- Bacteriophages offer targeted therapy but face rapid resistance development.
- Phage resistance can alter bacterial virulence and immune evasion.
Purpose of the Study:
- To investigate the mechanisms of phage resistance in MDRAB.
- To develop adapted bacteriophages for overcoming resistance.
- To evaluate combination therapy of phages and antibiotics against MDRAB.
Main Methods:
- Isolation of a lytic bacteriophage (WYF231108.1) targeting a clinical MDRAB isolate.
- Generation of phage-resistant MDRAB derivatives through serial passage.
- Genomic and phenotypic analysis of resistant strains and adapted phages.
- In vitro and in vivo evaluation of phage-antibiotic combination therapy.
Main Results:
- Phage resistance in MDRAB was linked to capsule attenuation and reduced virulence.
- Adapted phages regained activity against resistant strains.
- Phage-antibiotic combinations suppressed resistant MDRAB outgrowth in vitro.
- Combination therapy improved survival in murine infection models.
Conclusions:
- Phage resistance in MDRAB involves an evolutionary trade-off with reduced pathogenicity.
- Capsule attenuation in resistant strains creates a therapeutic vulnerability.
- Adapted phage-antibiotic regimens offer a promising strategy to combat MDRAB infections.
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