Dataset Information

Identification of commonly expressed exoproteins and proteolytic cleavage events by proteomic mining of clinically relevant UK isolates of Staphylococcus aureus.

ABSTRACT: The range of exoproteins and core exoproteome of 14 Staphylococcus aureus isolates representing major lineages associated with asymptomatic carriage and clinical disease in the UK was identified by MS proteomics using a combined database incorporating sequences derived from 39 S. aureus genomes. In all, 632 different proteins were identified and, of these, only 52 (8?%) were found in all 14 isolates whereas 144 (23?%) were found in just a single isolate. Comparison of the observed mass of each protein (based on migration by SDS-PAGE) with its predicted mass (based on amino acid sequence) suggested that 95?% of the proteins identified were not subject to any major post-translational modification. Migration of 5?% of the proteins was not as expected: 1?% of the proteins migrated at a mass greater than predicted, while 4?% appeared to have undergone proteolytic cleavage; these included SsaA2, Aur, SspP, Ebh as well as BlaR1, MecR1, FsH, OatA and LtaS. Intriguingly, a truncated SasG was produced by a single CC8 USA300-like strain. The analysis provided evidence of the marked heterogeneity in protein expression by S. aureus in broth, while yielding a core but narrow common exoproteome.

SUBMITTER: Smith DS

PROVIDER: S-EPMC5320583 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Identification of commonly expressed exoproteins and proteolytic cleavage events by proteomic mining of clinically relevant UK isolates of Staphylococcus aureus.

Smith Debra S DS Siggins Matthew K MK Gierula Magdalena M Pichon Bruno B Turner Claire E CE Lynskey Nicola N NN Mosavie Mia M Kearns Angela M AM Edwards Robert J RJ Sriskandan Shiranee S

Microbial genomics 20160223 2

The range of exoproteins and core exoproteome of 14 Staphylococcus aureus isolates representing major lineages associated with asymptomatic carriage and clinical disease in the UK was identified by MS proteomics using a combined database incorporating sequences derived from 39 S. aureus genomes. In all, 632 different proteins were identified and, of these, only 52 (8 %) were found in all 14 isolates whereas 144 (23 %) were found in just a single isolate. Comparison of the observed ...[more]

PMID: 28348843

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Project description:BACKGROUND:Neuronal cell loss contributes to the pathology of acute and chronic neurodegenerative diseases, including Alzheimer's disease (AD). It remains crucial to identify molecular mechanisms sensitizing neurons to various insults and cell death. To date, the multifunctional, autophagy-related protein Beclin 1 has been shown to be both necessary and sufficient for neuronal integrity in neurodegenerative models associated with protein aggregation. Interestingly, besides its role in cellular homeostasis, Beclin 1 has also been ascribed a role in apoptosis. This makes it critical to elucidate whether Beclin 1 regulates neuronal death and survival across neurodegenerative conditions independent of protein clearance. Here, we provide experimental evidence for a direct functional link between proteolytic cleavage of Beclin 1 and apoptotic neuronal cell loss in two independent models of neurodegeneration in vivo. METHODS:Proteolytic cleavage of Beclin 1 was characterized in lysates of human AD brain samples. We developed viral tools allowing for the selective neuronal expression of the various Beclin 1 forms, including Beclin 1 cleavage products as well as a cleavage-resistant form. The effect of these Beclin 1 forms on survival and integrity of neurons was examined in models of acute and chronic neurodegeneration in vitro and in vivo. Markers of neuronal integrity, neurodegeneration and inflammation were further assessed in a Kainic acid-based mouse model of acute excitotoxic neurodegeneration and in a hAPP-transgenic mouse model of AD following perturbation of Beclin 1 in the susceptible CA1 region of the hippocampus. RESULTS:We find a significant increase in caspase-mediated Beclin 1 cleavage fragments in brain lysates of human AD patients and mimic this phenotype in vivo using both an excitotoxic and hAPP-transgenic mouse model of neurodegeneration. Surprisingly, overexpression of the C-terminal cleavage-fragment exacerbated neurodegeneration in two distinct models of degeneration. Local inhibition of caspase activity ameliorated neurodegeneration after excitotoxic insult and prevented Beclin 1 cleavage. Furthermore, overexpression of a cleavage-resistant form of Beclin 1 in hippocampal neurons conferred neuroprotection against excitotoxic and Amyloid beta-associated insults in vivo. CONCLUSIONS:Together, these findings indicate that the cleavage state of Beclin 1 determines its functional involvement in both neurodegeneration and neuroprotection. Hence, manipulating the cleavage state of Beclin 1 may represent a therapeutic strategy for preventing neuronal cell loss across multiple forms of neurodegeneration.

Dataset Information

Identification of commonly expressed exoproteins and proteolytic cleavage events by proteomic mining of clinically relevant UK isolates of Staphylococcus aureus.

Publications

Identification of commonly expressed exoproteins and proteolytic cleavage events by proteomic mining of clinically relevant UK isolates of <i>Staphylococcus aureus</i>.

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