Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies

Koedijk, Dennis G. A. M.; Pastrana, Francisco Romero; Hoekstra, Hedzer; Berg, Sanne van den; Back, Jaap Willem; Kerstholt, Carolien; Prins, Rianne C; Bakker-Woudenberg, Irma A. J. M.; Dijl, Jan Maarten van; Buist, Girbe

doi:10.1038/s41598-017-08182-9

Cited by 14 publications

(20 citation statements)

References 49 publications

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“…Additionally, the amino acid residues that are essential for the function of FtsN are absent from Tgl, SceD, and IsaA (data not shown). Possibly, this region can facilitate the interaction of Tgl with cell wall, as has been proposed for the corresponding region of IsaA [35].…”

Section: Discussionmentioning

confidence: 74%

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A Kayvirus Distant Homolog of Staphylococcal Virulence Determinants and VISA Biomarker Is a Phage Lytic Enzyme

Głowacka-Rutkowska

Ulatowska

Empel

et al. 2020

Viruses

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Staphylococcal bacteriophages of the Kayvirus genus are candidates for therapeutic applications. One of their proteins, Tgl, is slightly similar to two staphylococcal virulence factors, secreted autolysins of lytic transglycosylase motifs IsaA and SceD. We show that Tgl is a lytic enzyme secreted by the bacterial transport system and localizes to cell peripheries like IsaA and SceD. It causes lysis of E. coli cells expressing the cloned tgl gene, but could be overproduced when depleted of signal peptide. S. aureus cells producing Tgl lysed in the presence of nisin, which mimics the action of phage holin. In vitro, Tgl protein was able to destroy S. aureus cell walls. The production of Tgl decreased S. aureus tolerance to vancomycin, unlike the production of SceD, which is associated with decreased sensitivity to vancomycin. In the genomes of kayviruses, the tgl gene is located a few genes away from the lysK gene, encoding the major endolysin. While lysK is a late phage gene, tgl can be transcribed by a host RNA polymerase, like phage early genes. Taken together, our data indicate that tgl belongs to the kayvirus lytic module and encodes an additional endolysin that can act in concert with LysK in cell lysis.

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Section: Discussionmentioning

confidence: 74%

“…The second region (pos. corresponds to the region of IsaA essential for binding to cell wall [35]. The third region homologous to the PRK10927 motif in Tgl is the least conserved.…”

Section: Analysis Of the Amino Acid Sequence Of Tgl Proteinmentioning

confidence: 99%

A Kayvirus Distant Homolog of Staphylococcal Virulence Determinants and VISA Biomarker Is a Phage Lytic Enzyme

Głowacka-Rutkowska

Ulatowska

Empel

et al. 2020

Viruses

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show abstract

“…The remaining regions encompass the Tgl fragment between aa residues 28 and 89, the region of PRK10927 motif and the core lisozyme-like domain motif. The first of these regions corresponds to the region of IsaA essential for the binding to cell wall [35]. The second region, homologous to the PRK10927 motif in Tgl is the least conserved.…”

Section: Analysis Of the Amino Acid Sequence Of Tgl Proteinmentioning

confidence: 99%

“…IsaA is a major S. aureus immunodominant antigen, which is surface-exposed and has been identified in exoproteoms of all tested S. aureus clinical isolates studied [19,31,32,33,34]. It is bound to S. aureus cell wall by non-covalent interactions [35]. Diseases associated with S. aureus colonization, including sepsis caused by methicillin resistant S. aureus (MRSA), are associated with the increased IgG response against IsaA [36,37,38,39].…”

Section: Introductionmentioning

confidence: 99%

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A <em>Kayvirus</em> Distant Homolog of Staphylococcal Virulence Determinats and VISA Biomarker is a Phage Lytic Enzyme That Decreases <em>S. aureus</em> Tolerance to Vancomycin

Głowacka-Rutkowska¹,

Ulatowska²,

Empel³

et al. 2019

Preprint

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Staphylococcal bacteriophages of Kayvirus genus are candidates for therapeutic applications. One of their proteins, Tgl, is slightly similar to staphylococcal virulence factors, secreted autolysins of lytic transglycosylase motifs, IsaA and SceD. We show that Tgl is also a lytic enzyme secreted by bacterial transport system and localizes to cell peripheries, like IsaA and SceD. It caused lysis of E. coli cells expressing the cloned tgl gene, but could be overproduced when depleted of signal peptide. S. aureus cells producing Tgl lysed in the presence of nisin, which mimics the action of phage holin. In vitro, Tgl protein was able to destruct S. aureus cell walls. The production of Tgl decreased S. aureus tolerance to vancomycin, unlike the production of SceD, which is associated with the decreased sensitivity to vancomycin. In the genomes of kayviruses, the tgl gene is located a few genes away from gene lysK, encoding the major endolysin. While lysK is a late phage gene, tgl can be transcribed by a host RNA polymerase, as are phage early genes. Taken together our data indicate that tgl is a part of kayviruses lytic module and encodes an additional endolysin which can act in concert with LysK in cell lysis.

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Bactericidal fully human single‐chain fragment variable antibodies protect mice against methicillin‐resistant Staphylococcusaureus bacteraemia

et al. 2021

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Objectives. The increasing prevalence of antibiotic-resistant Staphylococcus aureus, besides the inadequate numbers of effective antibiotics, emphasises the need to find new therapeutic agents against this lethal pathogen. Methods. In this study, to obtain antibody fragments against S. aureus, a human single-chain fragment variable (scFv) library was enriched against living methicillin-resistant S. aureus (MRSA) cells, grown in three different conditions, that is human peripheral blood mononuclear cells with plasma, whole blood and biofilm. The antibacterial activity of scFvs was evaluated by the growth inhibition assay in vitro. Furthermore, the therapeutic efficacy of anti-S. aureus scFvs was appraised in a mouse model of bacteraemia. Results. Three scFv antibodies, that is MEH63, MEH158 and MEH183, with unique sequences, were found, which exhibited significant binding to S. aureus and reduced the viability of S. aureus in in vitro inhibition assays. Based on the results, MEH63, MEH158 and MEH183, in addition to their combination, could prolong the survival rate, reduce the bacterial burden in the blood and prevent inflammation and tissue destruction in the kidneys and spleen of mice with MRSA bacteraemia compared with the vehicle group (treated with normal saline). Conclusion. The combination therapy with anti-S. aureus scFvs and conventional antibiotics might shed light on the treatment of patients with S. aureus infections.

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Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies

Cited by 14 publications

References 49 publications

A Kayvirus Distant Homolog of Staphylococcal Virulence Determinants and VISA Biomarker Is a Phage Lytic Enzyme

A Kayvirus Distant Homolog of Staphylococcal Virulence Determinants and VISA Biomarker Is a Phage Lytic Enzyme

A <em>Kayvirus</em> Distant Homolog of Staphylococcal Virulence Determinats and VISA Biomarker is a Phage Lytic Enzyme That Decreases <em>S. aureus</em> Tolerance to Vancomycin

Bactericidal fully human single‐chain fragment variable antibodies protect mice against methicillin‐resistant Staphylococcusaureus bacteraemia

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