TY - JOUR
T1 - Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient
AU - Wheatley, Rachel M
AU - Caballero, Julio Diaz
AU - van der Schalk, Thomas E
AU - De Winter, Fien H R
AU - Shaw, Liam P
AU - Kapel, Natalia
AU - Recanatini, Claudia
AU - Timbermont, Leen
AU - Kluytmans, Jan
AU - Esser, Mark
AU - Lacoma, Alicia
AU - Prat-Aymerich, Cristina
AU - Oliver, Antonio
AU - Kumar-Singh, Samir
AU - Malhotra-Kumar, Surbhi
AU - Craig MacLean, R
PY - 2022/11/22
Y1 - 2022/11/22
N2 - 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 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.
AB - 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 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.
KW - Humans
KW - Pseudomonas aeruginosa/genetics
KW - Anti-Bacterial Agents/pharmacology
KW - Meropenem/pharmacology
KW - Lung
KW - Bacteria
KW - Intensive Care Units
U2 - 10.1038/s41467-022-34101-2
DO - 10.1038/s41467-022-34101-2
M3 - Article
C2 - 36414617
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6523
ER -