Functional Characterization of Acinetobacter baumannii Lacking the RNA Chaperone Hfq

Abstract

The RNA chaperone Hfq is involved in the riboregulation of diverse genes via small RNAs. Recent studies have demonstrated that Hfq contributes to the stress response and the virulence of several pathogens, and the roles of Hfq vary among bacterial species. Here, we attempted to elucidate the role of Hfq in Acinetobacter baumannii ATCC 17978. In the absence of hfq, A. baumannii exhibited retarded cell growth and was highly sensitive to environmental stress, including osmotic and oxidative pressure, pH, and temperature. Compared to the wild-type, the Hfq mutant had reduced outer membrane vesicles secretion and fimbriae production as visualized by atomic force microscopy. The absence of hfq reduced biofilm formation, airway epithelial cell adhesion and invasion, and survival in macrophage. Further, the hfq mutant induced significantly higher IL-8 levels in airway epithelial cells, which would promote bacterial clearance by the host. In addition to results similar to those reported for other bacteria, our findings demonstrate that Hfq is required in the regulation of the iron-acquisition system via downregulating the bauA and basD genes, the stress-related outer membrane proteins carO, A1S_0820, ompA, and nlpE, and the stress-related cytosolic proteins uspA and groEL. Our data indicate that Hfq plays a critical role in environmental adaptation and virulence in A. baumannii by modulating stress responses, surface architectures, and virulence factors. This study is the first to illustrate the functional role of Hfq in A. baumannii.

Coping with low water activities and osmotic stress in Acinetobacter baumannii: significance, current status and perspectives

“…Some regulatory systems involved in osmo‐sensing in Acinetobacter are known. A regulatory protein involved in the general stress response, including osmotic stress, as well as in pathogenesis, is the RNA chaperone Hfq (Kuo et al ., ). Hfq is important for survival under dry conditions (see above), and moreover, a deletion mutant in A. baumannii exhibited a dramatic growth defect at high osmolarity (ca.…”

“…Notably, Hfq of A. baumannii has an extended C‐terminus, which distinguishes the protein from Hfq of other Gram‐negative pathogens. This C‐terminus nearly doubles the size of the protein and is important for full function of the RNA chaperone; accordingly, a mutant with a truncated Hfq was more susceptible to desiccation than the wild type (Kuo et al ., ; Sharma et al ., ).…”

Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection

“…Hfq deficiency retards cell growth and enhances cellular sensitivity to environment stress. The expression level of OmpA in Hfq mutant strain is dramatically lower than that in a wild type strain [69]. In addition, there is a causal correlation between biofilm formation and AbOmpA expression in A.baumannii under the treatment of antibiotics at sub-minimum inhibitory concentrations (MIC).…”

The Outer Membrane Proteins OmpA, CarO, and OprD of Acinetobacter baumannii Confer a Two-Pronged Defense in Facilitating Its Success as a Potent Human Pathogen

“…However, growth conditions like temperature, oxygen content, osmolarity, and media components regulate the expression of porins in A. baumannii ( Hwa et al, 2010 ; Fernando and Kumar, 2012 ; Bazyleu and Kumar, 2014 ). Transcriptional and post-transcriptional regulatory networks ( Kuo et al, 2017 ; Sharma et al, 2018 ) also determine the virulence and antibiotic resistance of A. baumannii .…”