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Updated: Jul 5, 2026
The Multifaceted Benefits of Protein Co-expression in Escherichia coli
Published on: February 5, 2015
Individual and synergistic effects of rabbit granulocyte proteins on Escherichia coli
1Department of Microbiology, New York University School of Medicine, New York 10016.
Abstract:
Affinity purification of crude acid extracts of rabbit polymorphonuclear leukocytes using Escherichia coli (J5) as adsorbent yields the bactericidal/permeability-increasing protein (BPI), two 15-kD species (p15s), and the two most potent (cationic) defensin species (neutrophil peptides [NP] -1 and -2). Tested in buffered isotonic medium, the relative antibacterial potency of these proteins against E. coli J5 is BPI (IC50 0.2 nM) > p15A (10 nM) > NP -1 (400 nM). Sublethal doses of p15A or NP-1 can synergize with BPI to decrease the dose required to inhibit the growth of E. coli by up to 50-fold. BPI and p15A display similar features of antibacterial action distinct from defensin NP-1, but NP-1 acts synergistically only with BPI and not with p15A. All aspects of the combined action of BPI and NP-1 resemble those observed with higher concentrations of BPI alone, implying that NP-1 enhances BPI potency. Neither NP-1 nor p15A alter the amount of BPI binding to E. coli but BPI enhances binding of p15A to E. coli, raising the possibility that synergy between these two proteins may occur at least partially at the level of binding. The potent synergistic actions of these proteins can also be demonstrated against serum-resistant clinical isolates of encapsulated E. coli tested in whole blood and plasma ex vivo, suggesting that such combined action may contribute to host defense in vivo.
Insights
Rabbit immune proteins, including bactericidal/permeability-increasing protein (BPI) and neutrophil peptides (NP)-1, show synergistic antibacterial action against E. coli. This combined effect enhances BPI
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMNs) are crucial for innate immunity, producing antimicrobial proteins.
- Bactericidal/permeability-increasing protein (BPI) and defensins (neutrophil peptides, NPs) are key PMN-derived antibacterial agents.
Purpose of the Study:
- To investigate the synergistic antibacterial activities of BPI, p15s, and defensins (NP-1, NP-2) against Escherichia coli.
- To elucidate the mechanisms underlying the observed synergistic interactions between these antimicrobial proteins.
Main Methods:
- Affinity purification of rabbit PMN extracts to isolate BPI, p15s, and NPs.
- Antibacterial assays in vitro to determine relative potencies and synergistic effects against E. coli J5.
- Ex vivo testing against serum-resistant E. coli clinical isolates in whole blood and plasma.
Main Results:
- BPI demonstrated the highest antibacterial potency (IC50 0.2 nM) against E. coli J5, followed by p15A (10 nM) and NP-1 (400 nM).
- Sublethal doses of p15A or NP-1 synergized with BPI, increasing E. coli growth inhibition by up to 50-fold.
- NP-1 synergized only with BPI, enhancing its potency, while BPI enhanced p15A binding to E. coli, suggesting a binding-level synergy.
Conclusions:
- BPI, p15A, and NP-1 exhibit potent synergistic antibacterial effects against E. coli, including serum-resistant strains.
- Synergy between BPI and NP-1 enhances BPI potency, potentially through mechanisms distinct from direct binding alterations.
- The combined action of these proteins may significantly contribute to host defense mechanisms in vivo.
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