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Histidine Utilization Is a Critical Determinant of Acinetobacter Pathogenesis.
Authors Lonergan ZR, Palmer LD, Skaar EP
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Infection and immunity
Year 2020
Date Published 6/1/2020
Volume : Pages 88 : Not Specified
PubMed Reference 32341119
Abstract Acinetobacter baumannii is a nosocomial pathogen capable of causing a range of
diseases, including respiratory and urinary tract infections and bacteremia.
Treatment options are limited due to the increasing rates of antibiotic
resistance, underscoring the importance of identifying new targets for
antimicrobial development. During infection, A. baumannii must acquire nutrients
for replication and survival. These nutrients include carbon- and nitrogen-rich
molecules that are needed for bacterial growth. One possible nutrient source
within the host is amino acids, which can be utilized for protein synthesis or
energy generation. Of these, the amino acid histidine is among the most
energetically expensive for bacteria to synthesize; therefore, scavenging
histidine from the environment is likely advantageous. We previously identified
the A. baumannii histidine utilization (Hut) system as being linked to nutrient
zinc homeostasis, but whether the Hut system is important for
histidine-dependent energy generation or vertebrate colonization is unknown.
Here, we demonstrate that the Hut system is conserved among pathogenic
Acinetobacter and regulated by the transcriptional repressor HutC. In addition,
the Hut system is required for energy generation using histidine as a carbon and
nitrogen source. Histidine was also detected extracellularly in the murine lung,
demonstrating that it is bioavailable during infection. Finally, the
ammonia-releasing enzyme HutH is required for acquiring nitrogen from histidine
in vitro, and strains inactivated for hutH are severely attenuated in a murine
model of pneumonia. These results suggest that bioavailable histidine in the
lung promotes Acinetobacter pathogenesis and that histidine serves as a crucial
nitrogen source during infection.


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