Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity

ABSTRACT Mechanically ventilated patients are at risk of contracting pneumonia. Therefore, these patients often receive prophylactic systemic antimicrobial therapy. Intriguingly however, a previous study showed that antimicrobial activity in bronchoalveolar aspirates (here referred to as “sputa”) fr...

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Autores principales:	Jolien Seinen, Rudolf Engelke, Mohammed R. Abdullah, Franziska Voß, Stephan Michalik, Vishnu M. Dhople, Willem Dieperink, Anne Marie G. A. de Smet, Uwe Völker, Jan Maarten van Dijl, Frank Schmidt, Sven Hammerschmidt
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Streptococcus pneumoniae mechanical ventilation sputum antimicrobial peptides immunoproteomics proteomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6c9f6b805eed4bd5ae06bb19ef52b18c
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spelling	oai:doaj.org-article:6c9f6b805eed4bd5ae06bb19ef52b18c2021-12-02T19:22:27ZSputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity10.1128/mSystems.00702-202379-5077https://doaj.org/article/6c9f6b805eed4bd5ae06bb19ef52b18c2021-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00702-20https://doaj.org/toc/2379-5077ABSTRACT Mechanically ventilated patients are at risk of contracting pneumonia. Therefore, these patients often receive prophylactic systemic antimicrobial therapy. Intriguingly however, a previous study showed that antimicrobial activity in bronchoalveolar aspirates (here referred to as “sputa”) from ventilated patients was only partially explained by antibiotic therapy. Here we report that sputa from these patients presented distinct proteome signatures depending on the presence or absence of antimicrobial activity. Moreover, we show that the same distinction applied to antibodies against Streptococcus pneumoniae, which is a major causative agent of pneumonia. Specifically, the investigated sputa that inhibited growth of S. pneumoniae, while containing subinhibitory levels of the antibiotic cefotaxime, presented elevated levels of proteins implicated in innate immune defenses, including complement and apolipoprotein-associated proteins. In contrast, S. pneumoniae-inhibiting sputa with relatively high cefotaxime concentrations or noninhibiting sputa contained higher levels of proteins involved in inflammatory responses, such as neutrophil elastase-associated proteins. In an immunoproteomics analysis, 18 out of 55 S. pneumoniae antigens tested showed significantly increased levels of IgGs in inhibiting sputa. Hence, proteomics and immunoproteomics revealed elevated levels of antimicrobial host proteins or S. pneumoniae antigen-specific IgGs in pneumococcal growth-inhibiting sputa, thus explaining their anti-pneumococcal activity. IMPORTANCE Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia. This suggests the presence of potentially protective antimicrobial agents in their lung environment. Our present study shows for the first time that bronchoalveolar aspirates, “sputa,” of ventilated patients in a Dutch intensive care unit were characterized by three distinct groups of proteome abundance signatures that can explain their anti-pneumococcal activity. Importantly, this anti-pneumococcal sputum activity was related either to elevated levels of antimicrobial host proteins or to antibiotics and S. pneumoniae-specific antibodies. Further, the sputum composition of some patients changed over time. Therefore, we conclude that our study may provide a novel tool to measure changes that are indicative of infection-related conditions in the lungs of mechanically ventilated patients.Jolien SeinenRudolf EngelkeMohammed R. AbdullahFranziska VoßStephan MichalikVishnu M. DhopleWillem DieperinkAnne Marie G. A. de SmetUwe VölkerJan Maarten van DijlFrank SchmidtSven HammerschmidtAmerican Society for MicrobiologyarticleStreptococcus pneumoniaemechanical ventilationsputumantimicrobial peptidesimmunoproteomicsproteomicsMicrobiologyQR1-502ENmSystems, Vol 6, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pneumoniae mechanical ventilation sputum antimicrobial peptides immunoproteomics proteomics Microbiology QR1-502
spellingShingle	Streptococcus pneumoniae mechanical ventilation sputum antimicrobial peptides immunoproteomics proteomics Microbiology QR1-502 Jolien Seinen Rudolf Engelke Mohammed R. Abdullah Franziska Voß Stephan Michalik Vishnu M. Dhople Willem Dieperink Anne Marie G. A. de Smet Uwe Völker Jan Maarten van Dijl Frank Schmidt Sven Hammerschmidt Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity
description	ABSTRACT Mechanically ventilated patients are at risk of contracting pneumonia. Therefore, these patients often receive prophylactic systemic antimicrobial therapy. Intriguingly however, a previous study showed that antimicrobial activity in bronchoalveolar aspirates (here referred to as “sputa”) from ventilated patients was only partially explained by antibiotic therapy. Here we report that sputa from these patients presented distinct proteome signatures depending on the presence or absence of antimicrobial activity. Moreover, we show that the same distinction applied to antibodies against Streptococcus pneumoniae, which is a major causative agent of pneumonia. Specifically, the investigated sputa that inhibited growth of S. pneumoniae, while containing subinhibitory levels of the antibiotic cefotaxime, presented elevated levels of proteins implicated in innate immune defenses, including complement and apolipoprotein-associated proteins. In contrast, S. pneumoniae-inhibiting sputa with relatively high cefotaxime concentrations or noninhibiting sputa contained higher levels of proteins involved in inflammatory responses, such as neutrophil elastase-associated proteins. In an immunoproteomics analysis, 18 out of 55 S. pneumoniae antigens tested showed significantly increased levels of IgGs in inhibiting sputa. Hence, proteomics and immunoproteomics revealed elevated levels of antimicrobial host proteins or S. pneumoniae antigen-specific IgGs in pneumococcal growth-inhibiting sputa, thus explaining their anti-pneumococcal activity. IMPORTANCE Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia. This suggests the presence of potentially protective antimicrobial agents in their lung environment. Our present study shows for the first time that bronchoalveolar aspirates, “sputa,” of ventilated patients in a Dutch intensive care unit were characterized by three distinct groups of proteome abundance signatures that can explain their anti-pneumococcal activity. Importantly, this anti-pneumococcal sputum activity was related either to elevated levels of antimicrobial host proteins or to antibiotics and S. pneumoniae-specific antibodies. Further, the sputum composition of some patients changed over time. Therefore, we conclude that our study may provide a novel tool to measure changes that are indicative of infection-related conditions in the lungs of mechanically ventilated patients.
format	article
author	Jolien Seinen Rudolf Engelke Mohammed R. Abdullah Franziska Voß Stephan Michalik Vishnu M. Dhople Willem Dieperink Anne Marie G. A. de Smet Uwe Völker Jan Maarten van Dijl Frank Schmidt Sven Hammerschmidt
author_facet	Jolien Seinen Rudolf Engelke Mohammed R. Abdullah Franziska Voß Stephan Michalik Vishnu M. Dhople Willem Dieperink Anne Marie G. A. de Smet Uwe Völker Jan Maarten van Dijl Frank Schmidt Sven Hammerschmidt
author_sort	Jolien Seinen
title	Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity
title_short	Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity
title_full	Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity
title_fullStr	Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity
title_full_unstemmed	Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity
title_sort	sputum proteome signatures of mechanically ventilated intensive care unit patients distinguish samples with or without anti-pneumococcal activity
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/6c9f6b805eed4bd5ae06bb19ef52b18c
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Sputum Proteome Signatures of Mechanically Ventilated Intensive Care Unit Patients Distinguish Samples with or without Anti-pneumococcal Activity

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