Journal
INFECTION AND IMMUNITY
Volume 88, Issue 7, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00118-20
Keywords
Acinetobacter; histidine; infection; pneumonia
Categories
Funding
- National Institutes of Health (NIH) [R01 AI101171]
- NIH [DK059637, DK020593, F31 AI136255, K99 HL143441]
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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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