Surface Anchoring of the Kingella kingae Galactan Is Dependent on the Lipopolysaccharide O-Antigen

Montoya, Nina R.; Porsch, Eric A.; Muñoz, Vanessa L.; Muszyński, Artur; Vlach, Jiří; Hahn, David K; Azadi, Parastoo; Sherman, Matthew E.; Yang, Hyojik; Chandler, Courtney E.; Ernst, Robert K.; Geme, Joseph W. St.

doi:10.1128/mbio.02295-22

Cited by 3 publications

(9 citation statements)

References 60 publications

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“…However, more recent work examining mutants lacking the pamABC genes and deficient in galactan/HMW LPS production retained resistance to polymyxins, indicating that the galactan on its own is dispensable for CAMP resistance (53). Conversely, mutants lacking the pamDE genes were significantly more susceptible to polymyxins, suggesting that the LMW LPS O-antigen is a primary driver of CAMP resistance in K. kingae (53). Identification of the novel structural relationship between the K. kingae LPS and galactan molecules has provided a mechanism for surface anchoring of the galactan exopolysaccharide and for the unique functionality of this exopolysaccharide in interactions with host immune components.…”

Section: Galactan Exopolysaccharidementioning

confidence: 99%

“…These functions suggest that galactan must be tethered to the bacterial surface by some mechanism. Recent work has revealed that surface tethering of the galactan is dependent on the K. kingae lipopolysaccharide (LPS) atypical O-antigen ( 53 ).…”

Section: Introductionmentioning

confidence: 99%

“…Initial characterization of the K. kingae LPS revealed that it varies greatly from the LPS of related species. Notably, resolution of purified LPS from wild type K. kingae revealed two modal clusters, including a low molecular weight (LMW) cluster that displays a ladder migration pattern and a high molecular weight (HMW) cluster that contains an additional polysaccharide component ( Figure 4B ) ( 53 ). The uniformity of the ladder migration pattern observed in the LMW LPS species suggested the presence of a repeating sugar unit, implying that K. kingae produces an atypical O-antigen.…”

Section: Introductionmentioning

confidence: 99%

“…Some proteins in other organisms that contain these folds are involved in LPS biosynthesis. The homology analysis of the pamD and pamE gene products and the location of the pamD and pamE genes immediately adjacent to the pamABC genes suggested that these gene products might function in K. kingae LPS biosynthesis and influence the structural association between the LPS and galactan ( Figure 4A ) ( 53 ). Deletion of pamD and pamE resulted in production of a truncated LPS lacking both the LMW and HMW LPS species, highlighting the essential role of the pamD and pamE genes in biosynthesis of the K. kingae atypical O-antigen ( 53 ).…”

Section: Introductionmentioning

confidence: 99%

“…The homology analysis of the pamD and pamE gene products and the location of the pamD and pamE genes immediately adjacent to the pamABC genes suggested that these gene products might function in K. kingae LPS biosynthesis and influence the structural association between the LPS and galactan ( Figure 4A ) ( 53 ). Deletion of pamD and pamE resulted in production of a truncated LPS lacking both the LMW and HMW LPS species, highlighting the essential role of the pamD and pamE genes in biosynthesis of the K. kingae atypical O-antigen ( 53 ). Furthermore, the loss of the HMW LPS species in K. kingae strains lacking the pamD and pamE genes established that surface anchoring of the galactan requires the atypical O-antigen ( 53 ).…”

Section: Introductionmentioning

confidence: 99%

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Pathogenic determinants of Kingella kingae disease

et al. 2022

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Kingella kingae is an emerging pediatric pathogen and is increasingly recognized as a leading etiology of septic arthritis, osteomyelitis, and bacteremia and an occasional cause of endocarditis in young children. The pathogenesis of K. kingae disease begins with colonization of the upper respiratory tract followed by breach of the respiratory epithelial barrier and hematogenous spread to distant sites of infection, primarily the joints, bones, and endocardium. As recognition of K. kingae as a pathogen has increased, interest in defining the molecular determinants of K. kingae pathogenicity has grown. This effort has identified numerous bacterial surface factors that likely play key roles in the pathogenic process of K. kingae disease, including type IV pili and the Knh trimeric autotransporter (adherence to the host), a potent RTX-family toxin (epithelial barrier breach), and multiple surface polysaccharides (complement and neutrophil resistance). Herein, we review the current state of knowledge of each of these factors, providing insights into potential approaches to the prevention and/or treatment of K. kingae disease.

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Section: Galactan Exopolysaccharidementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pathogenic determinants of Kingella kingae disease

et al. 2022

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Acquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella

et al. 2023

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The bacterial genus Kingella includes two pathogenic species, namely Kingella kingae and Kingella negevensis, as well as strictly commensal species. Both K. kingae and K. negevensis secrete a toxin called RtxA that is absent in the commensal species. Here we present a phylogenomic study of the genus Kingella, including new genomic sequences for 88 clinical isolates, genotyping of another 131 global isolates, and analysis of 52 available genomes. The phylogenetic evidence supports that the toxin-encoding operon rtxCA was acquired by a common ancestor of the pathogenic Kingella species, and that a preexisting type-I secretion system was co-opted for toxin export. Subsequent genomic reorganization distributed the toxin machinery across two loci, with 30-35% of K. kingae strains containing two copies of the rtxA toxin gene. The rtxA duplication is largely clonal and is associated with invasive disease. Assays with isogenic strains show that a single copy of rtxA is associated with reduced cytotoxicity in vitro. Thus, our study identifies key steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer, co-option of an existing secretion system, and gene duplication.

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Acquisition, co-option, and duplication of thertxtoxin system and the emergence of virulence inKingella

Morreale

Porsch

Kern

et al. 2022

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TheKingellagenus includes two pathogenic species, namelyK. kingaeandK. negevensis, as well as strictly commensal species. BothK. kingaeandK. negevensissecrete a toxin called RtxA that is absent in the commensal species. Phylogenetic analysis demonstrates that the toxin-encoding operonrtxCrtxAtolCwas acquired by a common ancestor of the pathogenicKingellaspecies and that a preexisting type I secretion system was co-opted for toxin export. Subsequent genomic reorganization distributed the toxin machinery across two loci, with 30-35% ofK. kingaestrains containing two copies of thertxAtoxin gene. ThertxAduplication is largely clonal and strongly associated with invasive disease. In assays with isogenic strains, a single copy ofrtxAwas associated with reduced virulence in vitro. This study establishes the critical steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer, co-option of an existing secretion system, and gene duplication.

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Surface Anchoring of the Kingella kingae Galactan Is Dependent on the Lipopolysaccharide O-Antigen

Cited by 3 publications

References 60 publications

Pathogenic determinants of Kingella kingae disease

Pathogenic determinants of Kingella kingae disease

Acquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella

Acquisition, co-option, and duplication of thertxtoxin system and the emergence of virulence inKingella

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