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Functional and structural characteristics of bacterial proteins that bind host cytokines.

ABSTRACT: Several human pathogens bind and respond to host cytokines, which can be considered a virulence mechanism that communicates defensive actions of the host to the pathogen. This review summarizes the current knowledge of bacterial cytokine-binding proteins, with a particular focus on their functional and structural characteristics. Many bacterial cytokine-binding proteins function in the development of infection and inflammation and mediate adhesion to host cells, suggesting multiple roles in pathogen-host interactions. The regions of the bacterial proteins that interact with host cytokines can display structural similarities to other proteins involved in cytokine signaling. However, there appears to be no central shared structural themes for bacterial cytokine-binding proteins, and they appear to possess structures that are different from the cytokine receptors of the host. Atomic-level information regarding receptor-cytokine interactions is needed to be able to disrupt these interactions and to elucidate the specific consequences of cytokine binding in a pathogen and host.

SUBMITTER: Hogbom M

PROVIDER: S-EPMC5810482 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Functional and structural characteristics of bacterial proteins that bind host cytokines.

Högbom Martin M Ihalin Riikka R

Virulence 20170825 8

Several human pathogens bind and respond to host cytokines, which can be considered a virulence mechanism that communicates defensive actions of the host to the pathogen. This review summarizes the current knowledge of bacterial cytokine-binding proteins, with a particular focus on their functional and structural characteristics. Many bacterial cytokine-binding proteins function in the development of infection and inflammation and mediate adhesion to host cells, suggesting multiple roles in path ...[more]

PMID: 28783440

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Project description:To initiate their life cycle, phages must specifically bind to the surface of their bacterial hosts. Long-tailed phages often interact with the cell surface using fibers, which are elongated intertwined trimeric structures. The folding and assembly of these complex structures generally requires the activity of an intra- or intermolecular chaperone protein. Tail fiber assembly (Tfa) proteins are a very large family of proteins that serve as chaperones for fiber folding in a wide variety of phages that infect diverse species. A recent structural study showed that the Tfa protein from Escherichia coli phage Mu (TfaMu) mediates fiber folding and stays bound to the distal tip of the fiber, becoming a component of the mature phage particle. This finding revealed the potential for TfaMu to also play a role in cell surface binding. To address this issue, we have here shown that TfaMu binds to lipopolysaccharide (LPS), the cell surface receptor of phage Mu, with a similar strength as to the fiber itself. Furthermore, we have found that TfaMu and the Tfa protein from E. coli phage P2 bind LPS with distinct specificities that mirror the host specificity of these two phages. By comparing the sequences of these two proteins, which are 93% identical, we identified a single residue that is responsible for their distinct LPS-binding behaviors. Although we have not yet found conditions under which Tfa proteins influence host range, the potential for such a role is now evident, as we have demonstrated their ability to bind LPS in a strain-specific manner.IMPORTANCE With the growing interest in using phages to combat antibiotic-resistant infections or manipulate the human microbiome, establishing approaches for the modification of phage host range has become an important research topic. Tfa proteins are a large family of proteins known previously to function as chaperones for the folding of phage fibers, which are crucial determinants of host range for long-tailed phages. Here, we reveal that some Tfa proteins are bi-functional, with the additional activity of binding to LPS, the surface binding receptor for many phages. This discovery opens up new potential avenues for altering phage host range through engineering of the surface binding specificity of Tfa proteins.

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Functional and structural characteristics of bacterial proteins that bind host cytokines.

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Functional and structural characteristics of bacterial proteins that bind host cytokines.

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