Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient
Wheatley, Rachel M.; Caballero, Julio Diaz; van der Schalk, Thomas E.; De Winter, Fien H.R.; Shaw, Liam P.; Kapel, Natalia; Recanatini, Claudia; Timbermont, Leen; Kluytmans, Jan; Esser, Mark; Lacoma, Alicia; Prat-Aymerich, Cristina; Oliver, Antonio; Kumar-Singh, Samir; Malhotra-Kumar, Surbhi; Craig MacLean, R.
(2022) Nature Communications, volume 13
(Article)
Abstract
Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host
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immunity profiling, and clinical data. Crucially, we show that lung colonization in the ICU was driven by the translocation of P. aeruginosa from the gut. Meropenem treatment for a suspected urinary tract infection selected for elevated resistance in both the gut and lung. However, resistance was driven by parallel evolution in the gut and lung coupled with organ specific selective pressures, and translocation had only a minor impact on AMR. These findings suggest that reducing intestinal colonization of Pseudomonas may be an effective way to prevent lung infections in critically ill patients.
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Keywords: Humans, Pseudomonas aeruginosa/genetics, Anti-Bacterial Agents/pharmacology, Meropenem/pharmacology, Lung, Bacteria, Intensive Care Units, General Chemistry, General Biochemistry,Genetics and Molecular Biology, General, General Physics and Astronomy, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Funding Information: This research was supported by Wellcome Trust Grant (106918/Z/15/Z) and the Innovative Medicines Initiative Joint Undertaking under COMBACTE-MAGNET (Combatting Bacterial Resistance in Europe-Molecules against Gram-negative Infections, grant agreement no. 115737) and COMBACTE-NET (Combatting Bacterial Resistance in Europe-Networks, grant agreement no. 115523), resources of which are composed of financial contribution from the European Union’s Seventh Framework Program (FP7/2007-2013) and EFPIA companies’ in kind contribution. We thank the Oxford Genomics Center (funded by Wellcome Trust Grant 203141/Z/16/Z) for the generation and initial processing of Illumina sequence data. We thank the local ASPIRE ICU research team for their contribution to this project at Hospital Universitari Germans Trias i Pujol and the WP3A working group for assistance with project. Publisher Copyright: © 2022, The Author(s). © 2022. The Author(s).
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