Invasive Acinetobacter baumannii ABC141 strain relies on the twin-arginine translocation export system for adhesion
Charline Debruyne1,2, Landon Hodge1, Karsten Hokamp3
1Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Abstract:
Acinetobacter baumannii is associated with severe hospital-acquired, multi-drug-resistant infections worldwide, causing significant mortality and morbidity in intensive care patients or those under prolonged hospitalization. Multiple studies have recently shown that a proportion of circulating clinical isolates establish a transient multiplication niche inside phagocytic and non-phagocytic eukaryotic cells. We have previously demonstrated that the A. baumannii ABC141 strain invades human endothelial and epithelial cells, where it efficiently multiplies without induction of cytotoxicity. Here, we show that ABC141 adhesion, invasion and intracellular multiplication depend on the growth stage, being most efficient in the exponential growth phase. To define the gene expression signature most favourable to an intracellular lifestyle, a transcriptomic comparison was carried out between exponentially grown ABC141 and cultures in the stationary phase. Although most of the pathways identified reflected growth-related metabolic changes, we observed an up-regulation of the twin-arginine translocation (Tat) export system. Analysis of a mutant strain lacking the tatABC operon revealed that this export system is required only for adhesion to host cells, but not for invasion or intracellular multiplication. These data highlight a new role for the Tat export pathway in A. baumannii pathogenesis.
Insights
Acinetobacter baumannii efficiently invades host cells during its exponential growth phase. The twin-arginine translocation (Tat) export system is crucial for bacterial adhesion, but not invasion or intracellular multiplication, revealing a novel role in pathogenesis.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Acinetobacter baumannii causes severe, multi-drug-resistant hospital-acquired infections.
- Clinical isolates can invade and multiply within eukaryotic host cells.
- Previous work showed strain ABC141 invades and multiplies intracellularly without causing cytotoxicity.
Purpose of the Study:
- To investigate the growth phase-dependent characteristics of A. baumannii intracellular survival.
- To identify gene expression changes associated with intracellular lifestyle.
- To elucidate the role of the twin-arginine translocation (Tat) export system in A. baumannii pathogenesis.
Main Methods:
- Transcriptomic comparison of exponentially and stationary phase A. baumannii ABC141 cultures.
- Analysis of a tatABC operon mutant strain.
- Assessment of bacterial adhesion, invasion, and intracellular multiplication in host cells.
Main Results:
- Bacterial adhesion, invasion, and intracellular multiplication are most efficient in the exponential growth phase.
- The twin-arginine translocation (Tat) export system is upregulated in exponentially grown cells.
- A tatABC mutant showed impaired adhesion but retained invasion and intracellular multiplication capabilities.
Conclusions:
- Bacterial growth phase significantly influences the ability of A. baumannii to interact with host cells.
- The Tat export system plays a previously unrecognized role in A. baumannii adhesion to host cells.
- These findings offer new insights into the pathogenesis of A. baumannii infections.
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