TL;DR
An extensive insight is provided into the dual role of SpA as a virulence factor in S. aureus pathogenesis and its widespread application in biotechnology, including its vital role in affinity purification of polyclonal and monoclonal antibodies.
Protein A (SpA), a cell wall-associated protein of Staphylococcus aureus, is an immunoglobulin (Ig) binding molecule with high affinity to the Fc moiety of IgG. It can help S. aureus for effective shielding from recognition and opsonization by immune cells, thereby promoting bacterial immune evasion. Since its recognition in the early 1980s, diverse applications have been developed across biotechnology, medicine, and biochemical research, using both native and recombinant SpA variants produced in various host cells. This review provides a comprehensive overview of the major applications of SpA, with an emphasis on techniques that progressed to commercially available tools/platforms. These applications are based on its Ig-binding capability, including purification of monoclonal antibodies in biopharmaceutical manufacturing, selective isolation of antibodies in diagnostic workflows, integration into serological assays or biosensor systems, and use as a fusion partner/tag for capturing recombinant proteins.
Summary Background Acinetobacter baumannii is a critical global health threat due to multidrug resistance and high mortality. Although antimicrobial resistance mechanisms are well characterised, the virulence determinants that drive severe infections remain poorly understood. Methods We screened 89 carbapenem-resistant clinical isolates of A. baumannii for virulence in animal infection models and combined comparative genomics with functional assays to identify virulence factors. An immunoglobulin-binding protein from A. baumannii (ImbA) encoded on the type D plasmid was selected and characterised. Protein–immunoglobulin interactions were analysed by pull-down and biolayer interferometry. Additional ImbA inhibition of IgG–Fcγ receptor binding by flow cytometry were tested. Protective efficacy was evaluated in mice using vaccination or anti-ImbA antibodies. Findings A type D plasmid was consistently linked to high virulence in clinical isolates. The deletion of plasmid-encoded ImbA attenuated virulence. ImbA bound murine IgA and IgG with high affinity. The binding to the Fc region of IgG disrupted IgG–Fcγ receptor interactions. Vaccination with recombinant ImbA improved survival and reduced bacterial dissemination in female mice with anti-ImbA antibodies partially protecting against lethal infection. Bacterial burdens in the blood were reduced in treated groups. Interpretation Our study demonstrates ImbA as an unrecognised plasmid-encoded virulence factor in A. baumannii. By intercepting host immunoglobulins, ImbA drives immune evasion and hypervirulence. Blocking ImbA by vaccination and antibody therapy restored host defence and improved outcomes in female mice, highlighting ImbA as a non-antibiotic therapeutic target with potential against multidrug-resistant A. baumannii. Funding Bio&Medical Technology Development Program of the National Research Foundation (NRF), funded by the Korean government (MSIT) (No. RS-2023-00219213); Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program.
Natural killer (NK) cells are innate lymphocytes acting as the key effector cells capable of recognizing and eliminating infected and transformed cells without prior sensitization. Their role in antibacterial defense, inflammatory response regulation and modulation of reproductive processes has been attracting increasing attention. In this regard, of particular interest are opportunistic bacteria of the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) characterized by high virulence, a prominent potential for developing multiple antibiotic resistance, being a lead cause of severe nosocomial infections, especially in immunocompromised patients. Pathogens of the ESKAPE produce a wide range of cell wall structural components (lipopolysaccharides, peptide glycans, lipoteichoic acids, capsular polysaccharides) as well as secreted virulence factors (pore-forming toxins, proteases, superantigen-like proteins, extracellular membrane vesicles) that can directly modulate immune cell functional activity. This review systematizes current literature data regarding the mechanisms underlying interplay between products of ESKAPE pathogenic bacteria as well as NK cell receptor apparatus and effector functions. Intracellular signaling pathways (NF-κB, MAPK, JAK/STAT) activated upon binding of bacterial ligands to pattern recognition receptors (TLR2, TLR4, TLR9, NOD1/NOD2) and their impact on NK cell cytotoxic potential, cytokine secretion profile (IFNγ, TNFα, IL-1β), and survival are primarily delineated. In addition, the immunomodulatory mechanisms mediated by bacterial metabolites on dendritic cells and macrophages subsequently affecting NK cell activation are discussed as well. Understanding the complex network of molecular crosstalk between ESKAPE pathogen metabolites and NK cells is fundamental for developing novel immunotherapy strategies for drug-resistant infections, designing adjuvant drugs based on bacterial components as well as correcting immune disorders in critical conditions. Altogether, it opens up a new avenue to a personalized treatment approach for patients with severe nosocomial infections.
It is shown that immunization with PDHC confers robust protection against lethal S. aureus strains, including MRSA, even in previously exposed hosts, as well as protecting against diverse S. aureus strains in multiple murine models.
Findings suggest that PGK may function as a moonlighting protein, playing an essential role in the interaction of S. aureus with its host through plasminogen binding.
A novel function of Ecb is revealed, the activation of basophils to produce IL-4 in an IgE-independent manner, and a dual Ecb contribution to immune evasion-by interfering with complement activation and skewing Th2 immunity-and a role in the development of allergic inflammation-by inducing IL-4 production is suggested.
