Human serum albumin alters specific genes that can play a role in survival and persistence in Acinetobacter baumannii

Abstract

In the past few decades Acinetobacter baumannii has emerged as a notorious nosocomial pathogen because of its ability to acquire genetic material and persist in extreme environments. Recently, human serum albumin (HSA) was shown to significantly increase natural transformation frequency in A. baumannii. This observation led us to perform transcriptomic analysis of strain A118 under HSA induction to identify genes that are altered by HSA. Our results revealed the statistically significant differential expression of 296 protein-coding genes, including those associated with motility, biofilm formation, metabolism, efflux pumps, capsule synthesis, and transcriptional regulation. Phenotypic analysis of these traits showed an increase in surface-associated motility, a decrease in biofilm formation, reduced activity of a citric acid cycle associated enzyme, and increased survival associated with zinc availability. Furthermore, the expression of genes known to play a role in pathogenicity and antibiotic resistance were altered. These genes included those associated with RND-type efflux pumps, the type VI secretion system, iron acquisition/metabolism, and ß-lactam resistance. Together, these results illustrate how human products, in particular HSA, may play a significant role in both survival and persistence of A. baumannii.

Cerebrospinal fluid (CSF) boosts metabolism and virulence expression factors inAcinetobacter baumannii

“…Thus, the net effect of CSF might be an increase in expression of this transporter, which leads to higher citrate intracellular concentrations that may help by increasing the rate of growth. These results are consistent with previous observations that the presence of HSA, a major component of CSF, in the culture medium is correlated with elevated expression of the citrate symporter in A. baumannii (22). Further supporting this data, exposure of A. baumannii to pleural fluid (PF), another HSA containing fluid, increases growth rate and survival of A. baumannii A118 (23).…”

“…Proteins of the CitMHS family transport citrate-Mg 2+ complex symport with one proton per complex molecule (26). It is of interest that increased citrate levels help survival of A. baumannii in certain conditions (22).…”

“…Numerous studies on twitching and surface-associated motility in A. baumannii A118 showed dependence on changes in light and temperature (30) as well as on the components of the growth media. In particular, addition of HSA resulted in increased motility and concomitantly upregulation of the cognate genes (22). Exposure of A. baumannii A118 to CSF increased the expression of pilW (log2fold 1.22), pilJ (log2fold change 0.43), fimA (log2fold change 3.09), fimB (log2fold change 2.32), and the fimbrial protein precursor AbA118F_3133 (log2fold change 1.91).…”

“…Previous work showed that the presence of PF is correlated with modifications of the expression of more than 1100 A. baumannii genes including many virulence factors such as motility, biofilm formation, efflux, T6SS, fibrinolytic activity and capsule genes (18), and with an increase in cytotoxicity and immune evasion (23). HSA, a component of PF, might be responsible for all or part of these effects (18,20,22). The experiments showed in previous sections indicate that CSF produces effects similar to those observed with PF such as an increase in cytotoxicity and changes in expression of virulence genes.…”

“…A. baumannii's success in causing numerous infections, where it gets in contact with different body components and fluids, must be the result of its capabilities to not only capture adequate genetic determinants but also regulate expression of the proper cell components (2,(13)(14)(15)(18)(19)(20). We have also previously documented that human serum albumin (HSA) and pleural fluid (HSA-containing fluid), affected A. baumannii behavior, triggering an adaptive response that modulates DNA uptake, cytotoxicity, immune evasion, stress responses and metabolism (18,(20)(21)(22).…”