TY - JOUR
T1 - Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection
AU - Wheatley, Rachel
AU - Caballero, Julio Diaz
AU - Kapel, Natalia
AU - Winter, Fien H. R. de
AU - Jangir, Pramod
AU - Quinn, Angus
AU - Barrio-Tofiño, Ester del
AU - López-Causapé, Carla
AU - Hedge, Jessica
AU - Torrens, Gabriel
AU - Schalk, Thomas Van der
AU - Xavier, Basil Britto
AU - Fernández-Cuenca, Felipe
AU - Arenzana, Angel
AU - Recanatini, Claudia
AU - Timbermont, Leen
AU - Sifakis, Frangiscos
AU - Ruzin, Alexey
AU - Ali, Omar
AU - Lammens, Christine
AU - Goossens, Herman
AU - Kluytmans, Jan
AU - Kumar-Singh, Samir
AU - Oliver, Antonio
AU - Malhotra-Kumar, Surbhi
AU - MacLean, Craig
PY - 2021/4/28
Y1 - 2021/4/28
N2 - It 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 of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, 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 suppressed wbpM mutants 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.
AB - It 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 of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, 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 suppressed wbpM mutants 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.
U2 - 10.1038/s41467-021-22814-9
DO - 10.1038/s41467-021-22814-9
M3 - Article
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
M1 - 2460
ER -