Citation: Arshad, H.; Siokis, A.; Franke, R.; Habib, A.; Alfonso, J.C.L.; Poliakova, Y.; Lücke, E.; Michaelis, K.; Brönstrup, M.; Meyer-Hermann, M.; et al. Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease. Cells 2022, 11, 2283. https://doi.org/10.3390/ cells11152283 Academic Editor: Matthew A Nugent Received: 17 June 2022 Accepted: 20 July 2022 Published: 24 July 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cells Article Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease Haroon Arshad 1,2,†,‡ , Anastasios Siokis 3,†,§ , Raimo Franke 4 , Aamna Habib 4, k , Juan Carlos López Alfonso 3,¶ , Yuliya Poliakova 5,** , Eva Lücke 6 , Katina Michaelis 6 , Mark Brönstrup 4 , Michael Meyer-Hermann 3 , Ursula Bilitewski 4 , Jordi Vila 5 , Laurent Abel 7,8,9 , Thomas Illig 10 , Jens Schreiber 6 and Frank Pessler 1,2,11, * 1 Research Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany; dr.haroonarshad@gmail.com 2 Research Group Biomarkers for Infectious Diseases, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany 3 Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; anastasiossio@gmail.com (A.S.); jc.atlantis@gmail.com (J.C.L.A.); mmh@theoretical-biology.de (M.M.-H.) 4 Department of Chemical Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; raimo.franke@helmholtz-hzi.de (R.F.); aamna.habib@tuf.edu.pk (A.H.); mark.broenstrup@helmholtz-hzi.de (M.B.); ursula.bilitewski@helmholtz-hzi.de (U.B.) 5 Department of Clinical Microbiology, Biomedical Diagnostic Centre (CDB), Hospital Clinic, School of Medicine, University of Barcelona, 08036 Barcelona, Spain; yuliya.poliakova@synlab.es (Y.P.); jvila@clinic.cat (J.V.) 6 Clinic for Pneumology, Otto-von-Guericke University, 39106 Magdeburg, Germany; eva.luecke@med.ovgu.de (E.L.); katina_i.m@hotmail.com (K.M.); jens.schreiber@med.ovgu.de (J.S.) 7 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, 75015 Paris, France; laurent.abel@inserm.fr 8 Imagine Institute, Paris Descartes University, 75015 Paris, France 9 Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA 10 Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany; illig.thomas@mh-hannover.de 11 Centre for Individualised Infection Medicine, 30625 Hannover, Germany * Correspondence: frank.pessler@helmholtz-hzi.de; Tel.: +49-511-220027-167; Fax: +49-(0)-511-220027-186 † These authors contributed equally to this work. ‡ Present affiliations: DHQ Hospital, Faisalabad 38000, Pakistan. § Present affiliations: Sanofi Deutschland, 60311 Frankfurt am Main, Germany. k Present affiliations: Department of Pharmaceutical Sciences, The University of Faisalabad, Faisalabad 38000, Pakistan. ¶ Present affiliations: New Yorker, 38108 Braunschweig, Germany. ** Present affiliations: SYNLAB Diagnosticos Globales, 28010 Madrid, Spain. Abstract: Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evalu- ated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach nor- mal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during Cells 2022, 11, 2283. https://doi.org/10.3390/cells11152283 https://www.mdpi.com/journal/cells