Dataset Information

Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases.

ABSTRACT: Most bacteria surround themselves with a peptidoglycan (PG) exoskeleton synthesized by polysaccharide polymerases called penicillin-binding proteins (PBPs). Because they are the targets of penicillin and related antibiotics, the structure and biochemical functions of the PBPs have been extensively studied. Despite this, we still know surprisingly little about how these enzymes build the PG layer in vivo. Here, we identify the Escherichia coli outer-membrane lipoproteins LpoA and LpoB as essential PBP cofactors. We show that LpoA and LpoB form specific trans-envelope complexes with their cognate PBP and are critical for PBP function in vivo. We further show that LpoB promotes PG synthesis by its partner PBP in vitro and that it likely does so by stimulating glycan chain polymerization. Overall, our results indicate that PBP accessory proteins play a central role in PG biogenesis, and like the PBPs they work with, these factors are attractive targets for antibiotic development.

SUBMITTER: Paradis-Bleau C

PROVIDER: S-EPMC3085243 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases.

Paradis-Bleau Catherine C Markovski Monica M Uehara Tsuyoshi T Lupoli Tania J TJ Walker Suzanne S Kahne Daniel E DE Bernhardt Thomas G TG

Cell 20101201 7

Most bacteria surround themselves with a peptidoglycan (PG) exoskeleton synthesized by polysaccharide polymerases called penicillin-binding proteins (PBPs). Because they are the targets of penicillin and related antibiotics, the structure and biochemical functions of the PBPs have been extensively studied. Despite this, we still know surprisingly little about how these enzymes build the PG layer in vivo. Here, we identify the Escherichia coli outer-membrane lipoproteins LpoA and LpoB as essentia ...[more]

PMID: 21183074

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Project description:Bacteria compete against related individuals by delivering toxins. In myxobacteria, a key delivery and kin discrimination mechanism is called outer membrane (OM) exchange (OME). Here, cells that display compatible polymorphic cell surface receptors recognize one another and bidirectionally transfer OM content. Included in the cargo is a suite of polymorphic SitA lipoprotein toxins. Consequently, OME between compatible cells that are not clonemates results in intoxication, while exchange between clonemates is harmonious because cells express a cognate repertoire of immunity proteins, which themselves are not transferred. SitA toxins belong to six nonhomologous families classified by sequence conservation within their N-terminal "escort domains" (EDs), while their C termini contain polymorphic nucleases that target the cytoplasmic compartment. To investigate how toxins delivered to the OM by OME translocate to the cytoplasm, we selected transposon mutants resistant to each family. Our screens identified eight genes that conferred resistance in a SitA family-specific manner. Most of these genes are predicted to localize to the cell envelope, and some resemble proteins that colicins exploit to gain cell entry. By constructing functional chimeric SitAs between families, we show that the ED determines the specificity of resistance. Importantly, a mutant that confers resistance to all six SitA families was discovered. This gene was named traC and plays an accessory role with traAB in OME. This work thus provides insight into the mechanism of kin discrimination in myxobacteria and provides working models for how SitA toxins exploit host proteins to gain cytoplasmic entry. IMPORTANCE Many bacterial species use diverse systems to deliver bacteriocins or toxins to neighboring competing cells. These systems are often selective in targeting cells that are related to themselves and therefore compete in the same niches for resources. How these systems specifically identify target cells and deliver toxins to particular cellular compartments is a fundamental question. This study uses the model social bacterium Myxococcus xanthus to unravel how its kin discrimination system, called outer membrane exchange, works. Along with the TraA polymorphic cell surface receptor that identifies related individuals with compatible receptors, this work discovered a new protein, called TraC, that functions in this discrimination system. Additionally, genetic screens identified host factors that are proposed to be involved in the cytoplasmic entry of lipoprotein toxins from the OM. This work complements and broadens our mechanistic understanding of how bacteria use transport systems to discriminate against related foes to build clonal populations.

Dataset Information

Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases.

Publications

Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases.

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