Zur-regulated lipoprotein A contributes to the fitness of Acinetobacter baumannii.

Acinetobacter baumannii is a notorious nosocomial pathogen that commonly infects severely ill patients. Zinc (Zn) is essential to survive and adapt to different environment and host niches in A. baumannii. Of the Zinc uptake regulator (Zur)-regulated genes in A. baumannii, the A1S_3412 gene encoding a Zur-regulated lipoprotein A (ZrlA) is critical for cell envelope integrity and overcoming antibiotic exposure. This study investigated whether ZrlA contributes to the fitness of A. baumannii in vitro and in vivo using the wildtype A. baumannii ATCC 17978, ΔzrlA mutant, and zrlAcomplemented strains. The ΔzrlA mutant showed reduced biofilm formation, surface motility, and adherence to and invasion of epithelial cells compared to the wild-type strain. In a mouse pneumonia model, the ?zrlA mutant showed significantly lower bacterial numbers in the blood than the wildtype strain. These virulence traits were restored in the zrlAcomplemented strain. Under static conditions, the expression of csuCDE, which are involved in the chaperone-usher pili assembly system, was significantly lower in the ΔzrlA mutant than in the wild-type strain. Moreover, the expression of the bfmR/S genes, which regulate the CsuA/BABCDE system, was significantly lower in the ΔzrlA mutant under static conditions than in the wild-type strain. Our results indicate that the zrlA gene plays a role in the fitness of A. baumannii by regulating the BfmR/S two-component system and subsequently the CsuA/BABCDE chaperone-usher pili assembly system, suggesting it as a potential target for anti-virulence strategies against A. baumannii.