Mechanism of resistance to phagocytosis and pulmonary persistence in mucoid Pseudomonas aeruginosa

Introduction Pseudomonas aeruginosa is known for its ability to form biofilms, which are dependent on the production of exopolysaccharides. During chronic colonization of the airway and biofilm formation, P. aeruginosa converts to a mucoid phenotype, indicating production of the exopolysaccharide alginate. The mucoid phenotype promotes resistance to phagocytic killing, but the mechanism has not been established. Methods and Results To better understand the mechanism of phagocytic evasion conferred by alginate production, Human (THP-1) and murine (MH-S) macrophage cell lines were used to determine the effects of alginate production on macrophage binding, signaling and phagocytosis. Phagocytosis assays using mucoid clinical isolate FRD1 and its non-mucoid algD mutant showed that alginate production inhibited opsonic and non-opsonic phagocytosis, but exogenous alginate was not protective. Alginate caused a decrease in binding to murine macrophages. Blocking antibodies to CD11b and CD14 showed that these receptors were important for phagocytosis and were blocked by alginate. Furthermore, alginate production decreased the activation of signaling pathways required for phagocytosis. Mucoid and non-mucoid bacteria induced similar levels of MIP-2 from murine macrophages. Discussion This study demonstrated for the first time that alginate on the bacterial surface inhibits receptor-ligand interactions important for phagocytosis. Our data suggest that there is a selection for alginate conversion that blocks the earliest steps in phagocytosis, leading to persistence during chronic pulmonary infections.

• Publication year

  2023

• Venue

  Frontiers in Cellular and Infection Microbiology

• Publication date

  2023-03-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fcimb.2023.1125901PMID 37009499PMCID 10050686
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• CD11b/CD18 (Mac-1) Is a Novel Surface Receptor for Extracellular Double-Stranded RNA To Mediate Cellular Inflammatory Responses

  2013cited by this paper
• Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective

  2012cited by this paper
• The cell biology of phagocytosis.

  2012cited by this paper
• Sequence-Verified Two-Allele Transposon Mutant Library for Pseudomonas aeruginosa PAO1

  2012cited by this paper
• Information processing during phagocytosis

  2012influential reference
• Step-Wise Loss of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion

  2011cited by this paper
• Complement and periodontitis.

  2010cited by this paper
• Pseudomonas aeruginosa Evasion of Phagocytosis Is Mediated by Loss of Swimming Motility and Is Independent of Flagellum Expression

  2010cited by this paper
• Myelin Activates FAK/Akt/NF-κB Pathways and Provokes CR3-Dependent Inflammatory Response in Murine System

  2010cited by this paper
• Effect of alginate on innate immune activation of macrophages.

  2009cited by this paper
• Pseudomonas aeruginosa in adults with chronic obstructive pulmonary disease

  2009cited by this paper
• Use of cell wall stress to characterize σ22 (AlgT/U) activation by regulated proteolysis and its regulon in Pseudomonas aeruginosa

  2009cited by this paper
• Cholesterol-Rich Membrane Rafts and Lyn Are Involved in Phagocytosis during Pseudomonas aeruginosa Infection1

  2008influential reference
• Innate immune activation and cystic fibrosis.

  2008cited by this paper
• Sphingosine Kinases and Sphingosine-1-Phosphate Are Critical for Transforming Growth Factor β-Induced Extracellular Signal-Regulated Kinase 1 and 2 Activation and Promotion of Migration and Invasion of Esophageal Cancer Cells

  2008cited by this paper
• Mucus structure and properties in cystic fibrosis.

  2007cited by this paper
• The AlgT-Dependent Transcriptional Regulator AmrZ (AlgZ) Inhibits Flagellum Biosynthesis in Mucoid, Nonmotile Pseudomonas aeruginosa Cystic Fibrosis Isolates

  2006cited by this paper
• Quantification of bacterial invasion into adherent cells by flow cytometry.

  2006cited by this paper
• Respiratory Burst: Role in Signal Transduction in Alveolar Macrophages

  2006cited by this paper
• Dectin-1: a signalling non-TLR pattern-recognition receptor

  2006cited by this paper
• Cell wall‐inhibitory antibiotics activate the alginate biosynthesis operon in Pseudomonas aeruginosa: roles of σ22 (AlgT) and the AlgW and Prc proteases

  2006cited by this paper
• Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

  2006influential reference
• Pathogen-host interactions in Pseudomonas aeruginosa pneumonia.

  2005cited by this paper
• The Alternative Sigma Factor AlgT Represses Pseudomonas aeruginosa Flagellum Biosynthesis by Inhibiting Expression of fleQ

  2005cited by this paper
• The Exopolysaccharide Alginate Protects Pseudomonas aeruginosa Biofilm Bacteria from IFN-γ-Mediated Macrophage Killing1

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• Cooperative Prosurvival Activity by ERK and Akt in Human Alveolar Macrophages is Dependent on High Levels of Acid Ceramidase Activity1

  2004cited by this paper
• Role of Alginate O Acetylation in Resistance of Mucoid Pseudomonas aeruginosa to Opsonic Phagocytosis

  2001cited by this paper
• Role of Alginate and Its O Acetylation in Formation of Pseudomonas aeruginosa Microcolonies and Biofilms

  2001cited by this paper
• Two distinct receptors mediate nonopsonic phagocytosis of different strains of Pseudomonas aeruginosa.

  2001cited by this paper
• Selective up-regulation of chemokine IL-8 expression in cystic fibrosis bronchial gland cells in vivo and in vitro.

  1998cited by this paper
• Involvement of CD14 and complement receptors CR3 and CR4 in nuclear factor-kappaB activation and TNF production induced by lipopolysaccharide and group B streptococcal cell walls.

  1998cited by this paper
• Pseudomonas aeruginosa-mediated cytotoxicity and invasion correlate with distinct genotypes at the loci encoding exoenzyme S

  1997cited by this paper
• Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia

  1996cited by this paper
• Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia.

  1996cited by this paper
• The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis

  1995cited by this paper
• Nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages and polymorphonuclear leukocytes requires the presence of the bacterial flagellum

  1995cited by this paper
• Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes and enhances viral replication in HIV-infected monocytic cells.

  1995cited by this paper
• Nonmotility and phagocytic resistance of Pseudomonas aeruginosa isolates from chronically colonized patients with cystic fibrosis

  1994cited by this paper
• Pseudomonas aeruginosa AlgG is a polymer level alginate C5-mannuronan epimerase

  1994cited by this paper
• Mechanism of conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients.

  1993cited by this paper
• Genetic analysis of the alginate biosynthetic gene cluster of Pseudomonas aeruginosa shows evidence of an operonic structure

  1993cited by this paper
• Resistance of mucoid Pseudomonas aeruginosa to nonopsonic phagocytosis by alveolar macrophages in vitro

  1988cited by this paper
• Mucoid Pseudomonas aeruginosa Resists Nonopsonic Phagocytosis by Human Neutrophils and Macrophages

  1987cited by this paper
• Flagella and motility alterations in Pseudomonas aeruginosa strains from patients with cystic fibrosis: relationship to patient clinical condition

  1985cited by this paper
• Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester.

  1982cited by this paper
• Genetic mapping of chromosomal determinants for the production of the exopolysaccharide alginate in a Pseudomonas aeruginosa cystic fibrosis isolate

  1981cited by this paper
• Antiphagocytic effect of Pseudomonas aeruginosa exopolysaccharide.

  1980cited by this paper
• Chromosomal genetics of Pseudomonas.

  1979cited by this paper
• Chromosomal genetics of Pseudomonas

  1979cited by this paper
• A new modification of the carbazole analysis: application to heteropolysaccharides.

  1968cited by this paper

• Epidemiological insights into Haemophilus influenzae and Pseudomonas aeruginosa persistent colonization in non-cystic fibrosis bronchiectasis patients: a longitudinal and multicenter study

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• Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infections

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