Abstract
Acinetobacter baumannii, a Gram-negative coccobacillus, has become a prevalent nosocomial health threat affecting the majority of hospitals both in the U.S. and around the globe. Microbial cell surface hydrophobicity (CSH) has previously been correlated with virulence, uptake by immune cells, and attachment to epithelial cells. A mutant strain of A. baumannii (ΔtrxA) lacking the redox protein thioredoxin A was found to be more hydrophobic than its wild type (WT) and complemented counterparts, as measured by both Microbial Adhesion to Hydrocarbon (MATH) and salt aggregation. The hydrophobicity of the mutant could be abrogated through treatment with sodium cyanoborohydride (SCBH). This modulation correlated with reduction of disulfide bonds, as SCBH was able to reduce 5,5′-dithio-bis-[2-nitrobenzoic acid] and treatment with the known disulfide reducer, β-mercaptoethanol, also decreased ΔtrxA CSH. Additionally, the ΔtrxA mutant was more readily taken up than WT by J774 macrophages and this differential uptake could be abrogated though SCBH treatment. When partitioned into aqueous and hydrophobic phases, ΔtrxA recovered from the hydrophobic partition was phagocytosed more readily than from the aqueous phase further supporting the contribution of CSH to A. baumannii uptake by phagocytes. A second Gram-negative bacterium, Francisella novicida, also showed the association of TrxA deficiency (FnΔtrxA) with increased hydrophobicity and uptake by J774 cells. We previously have demonstrated that modification of the type IV pilus system (T4P) was associated with the A. baumannii ΔtrxA phenotype, and the Francisella FnΔtrxA mutant also was found to have a marked T4P deficiency. Interestingly, a F. novicida mutant lacking pilT also showed increased hydrophobicity over FnWT. Collective evidence presented in this study suggests that Gram-negative bacterial thioredoxin mediates CSH through multiple mechanisms including disulfide-bond reduction and T4P modulation.
Highlights
The Gram-negative multi-drug resistant (MDR) pathogen Acinetobacter baumannii is an important cause of nosocomial infections in the United States and worldwide (Antunes et al, 2011; Clark et al, 2016; Wieland et al, 2018)
We explore the possible Thioredoxin A (TrxA)-dependent virulence mechanisms affecting hydrophobicity and present several lines of evidences to demonstrate that TrxA can modulate A. baumannii and other Gram-negative bacterial cell surface hydrophobicity (CSH) through disulfide-bond reduction and regulation of type IV pili
Our laboratory noted the differential binding of Congo Red dye to the cell wall of the wild type (WT) A. baumannii and a ΔtrxA mutant (May et al, 2019) which prompted further exploration into possible modulation of cell surface hydrophobicity by thioredoxin
Summary
The Gram-negative multi-drug resistant (MDR) pathogen Acinetobacter baumannii is an important cause of nosocomial infections in the United States and worldwide (Antunes et al, 2011; Clark et al, 2016; Wieland et al, 2018). A. baumannii has become increasingly drug resistant, as well as possessing the ability to survive on abiotic surfaces and resist desiccation (Fournier and Richet, 2006). This led the World Health Organization to recently list the organism as the top pathogen requiring research and identification of new antimicrobials for treatment (Tacconelli and Magrini, 2017). Stenotrophomonas maltophilia, a nosocomial pathogen, showed increased hydrophobicity associated with increased adhesion to abiotic surfaces and biofilm formation with decreased swimming (flagella) motility, but not twitching motility (Pompilio et al, 2008)
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