Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

• DOI: 10.1038/s41467-021-22814-9
• Publication Date: 2021-04-28T10:10:35Z
• Authors: Rachel Wheatley; Julio Diaz Caballero; Natalia Kapel; Fien H. R. de Winter; Pramod Jangir; Angus Quinn; Ester del Barrio-...; Carla López-Causapé; Jessica Hedge; Gabriel Torrens; Thomas Van der Sc...; Basil Britto Xavier; Felipe Fernández-...; Angel Arenzana; Claudia Recanatini; Leen Timbermont; Frangiscos Sifakis; Alexey Ruzin; Omar Ali; Christine Lammens; Herman Goossens; Jan Kluytmans; Samir Kumar-Singh; Antonio Oliver; Surbhi Malhotra-K...; Craig MacLean
• Keywords: 0301 basic medicine; Proteínas de la Membrana Bacteriana Externa; Porinas; General Physics and Astronomy; Bacterial Outer Membrane Proteins/genetics; Choque Hemorrágico; Proteínas de Transporte de Membrana; Drug Resistance, Multiple, Bacterial; Porins/genetics; Membrane Transport Proteins/genetics; Respiratory Tract Infections; Plasmids/genetics; Farmacorresistencia Bacteriana Múltiple; Persona de Mediana Edad; Research Support, Non-U.S. Gov't; Q; Infecciones por Pseudomonas; Plásmidos; Middle Aged; Humanos; Anti-Bacterial Agents; 3. Good health; Antibacterianos; Pseudomonas Infections/drug therapy; Pseudomonas aeruginosa; Proteínas Bacterianas; Engineering sciences. Technology; Bacterial Outer Membrane Proteins; Plasmids; Respiratory Tract Infections/diagnosis; Hydro-Lyases/genetics; Science; General Biochemistry,Genetics and Molecular Biology; Análisis de Secuencia de ADN; Porins; Microbial Sensitivity Tests; Shock, Hemorrhagic; Pseudomonas aeruginosa/drug effects; Article; Meropenem/therapeutic use; Selection, Genetic/genetics; Selección Genética; 03 medical and health sciences; Bacterial Proteins; Journal Article; Humans; Pseudomonas Infections; Selection, Genetic; Hydro-Lyases; Bacterial Proteins/genetics; Hidroliasas; Infecciones del Sistema Respiratorio; Membrane Transport Proteins; General Chemistry; Meropenem; Sequence Analysis, DNA; Drug Resistance, Multiple, Bacterial/genetics; Anti-Bacterial Agents/therapeutic use; Shock, Hemorrhagic/microbiology; Human medicine; Pruebas de Sensibilidad Microbiana

AbstractIt is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses ofPseudomonas aeruginosato treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressedP. aeruginosa, but a second wave of infection emerged due to the growth ofoprDandwbpMmeropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitnessoprDmutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressedwbpMmutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.