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pmid:31941798

Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping.

Roger Karlsson · Annika Thorsell · Margarita Gomila · Francisco Salvà-Serra · Hedvig E Jakobsson · Lucia Gonzales-Siles · Daniel Jaén-Luchoro · Susann Skovbjerg · Johannes Fuchs · Anders Karlsson · Fredrik Boulund · Anna Johnning · Erik Kristiansson · Edward R B Moore

Molecular & cellular proteomics : MCP · 2020 doi:10.1074/mcp.RA119.001667

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title
Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping.
doi
10.1074/mcp.RA119.001667
pmid
31941798
authors array · 14 items
[0]
Roger Karlsson
[1]
Annika Thorsell
[2]
Margarita Gomila
[3]
Francisco Salvà-Serra
[4]
Hedvig E Jakobsson
[5]
Lucia Gonzales-Siles
[6]
Daniel Jaén-Luchoro
[7]
Susann Skovbjerg
[8]
Johannes Fuchs
[9]
Anders Karlsson
[10]
Fredrik Boulund
[11]
Anna Johnning
[12]
Erik Kristiansson
[13]
Edward R B Moore
journal
Molecular & cellular proteomics : MCP
year
2020
abstract
Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.
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The mass spectrometry proteomics data (MSMS-spectra for all species-unique peptides presented in Tables I–IV, as well as raw-files and PD1.4 search files of representative clinical samples) have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifiers PXD014522.
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sections[22] "DATA AVAILABILITY" paragraph 2
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The mass spectrometry proteomics data (MSMS-spectra for all species-unique peptides presented in Tables I–IV, as well as raw-files and PD1.4 search files of representative clinical samples) have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifiers PXD014522.
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The mass spectrometry proteomics data (MSMS-spectra for all species-unique peptides presented in Tables I–IV, as well as raw-files and PD1.4 search files of representative clinical samples) have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifiers PXD014522.
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Discovery of species-unique peptide biomarkers of bacterial pathogens by tandem mass spectrometry-based proteotyping
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The peptide biomarker candidates of M. catarrhalis and the proteins from which they originate
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WP_003660336.1
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[2]
11
[3]
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[3]
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8
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[1]
33
[2]
10
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31
[2]
8
[3]
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[1]
33
[2]
13
[3]
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[2]
10
[3]
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The peptide biomarker candidates of S. pneumoniae and the proteins from which they originate
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Number of times detected in unique clinical samples
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12
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KDEAEAAFATIR
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Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping.
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The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. 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