Daily rhythms modulate Acinetobacter baumannii physiology impacting infection outcome and antibiotic-inactivating capacity

We recently demonstrated that the human pathogen Acinetobacter baumannii exhibits light-regulated daily and circadian rhythms, suggesting that the physiological state of the bacterium varies along the day. Because this temporal dimension may influence host-pathogen interactions, we investigated here whether key bacterial processes relevant to pathogenesis fluctuate according to light-dark-induced rhythms and whether these fluctuations impact infection outcome. In particular, β-lactamase activity displayed significant daily variation in several multidrug-resistant strains, with higher activity at the end of the light phase compared to the dark phase, in light-dark entrained cultures. Consistent with these findings, macrocolony ring formation also followed a rhythmic pattern. In addition, we show that both prior bacterial entrainment and the time of infection critically determine disease progression in a murine skin-wound infection model. Specifically, higher bacterial titers were recovered when light-dark entrained bacteria infected mice at the end of the dark phase (morning) with respect to infections caused by arrhythmic bacteria, while the opposite occurred in the evening. Together, these results demonstrate that A. baumannii displays diurnal regulation of physiological and pathogenic traits that influence infection dynamics and antibiotic-inactivating activity, introducing a new temporal dimension to bacterial pathogenesis with important implications for understanding disease progression and treatment strategies.