Journal Article

Acinetobacter baumannii Kills Fungi via a Type VI DNase Effector

Sun, Yu, Li, Dan, Luo, Zhao-Qing, Jie, Jing, Guan, Qingtian, Song, Lei, Chu, Xiao, Luo, Jingjing

2023

Overview

Acinetobacter baumannii is an increasing important nosocomial pathogen that is difficult to combat due to its ability to survive in harsh environments and the emergence of isolates that are resistant to multiple antibiotics. A better understanding of the mechanism underlying the toughness of A. baumannii may identify its Achilles’ heel, which will facilitate the development of novel preventive and treatment measures. Many Gram-negative bacteria deploy a type VI secretion system (T6SS) to inject toxins into target cells to promote their survival and replication in complex environments. Here, we report that Acinetobacter baumannii uses its T6SS to kill fungi and that the effector TafE ( ACX60_15365 ) is responsible for such killing. Although ectopically expressed TafE is toxic to both Escherichia coli and Saccharomyces cerevisiae , deletion of tafE only affects the antifungal activity of A. baumannii . We demonstrate that TafE is a DNase capable of targeting the nuclei of yeast cells and that an Ntox15 domain is essential for its ability to degrade DNA. Furthermore, our findings show that A. baumannii is protected from the toxicity of TafE by elaborating the immunity protein TaeI ( ACX60_15360 ), which antagonizes the activity of the effector by direct binding. The discovery of A. baumannii T6SS effectors capable of killing multiple taxonomically distinct microbes has shed light on a mechanism of the high-level fitness of this pathogen in environments characterized by scarce nutrients and the potential presence of diverse microorganisms. IMPORTANCE Acinetobacter baumannii is an increasing important nosocomial pathogen that is difficult to combat due to its ability to survive in harsh environments and the emergence of isolates that are resistant to multiple antibiotics. A better understanding of the mechanism underlying the toughness of A. baumannii may identify its Achilles’ heel, which will facilitate the development of novel preventive and treatment measures. In this study, our findings show that A. baumannii kills fungi with the DNase effector TafE injected into competitor cells by its type VI secretion system. A. baumannii is protected from the activity of TafE by the immunity protein TaeI, which inactivates the effector by direct binding. Our results suggest that inactivation of its T6SS or effectors may reduce the fitness of A. baumannii and increase the effectiveness of treatment by means such as antibiotics. Furthermore, our finding suggests that targeted degradation of TaeI may be an effective strategy to kill A. baumannii .

• Publisher: American Society for Microbiology
• Subject: Acinetobacter baumannii / Acinetobacter baumannii - genetics / Anti-Bacterial Agents - metabolism / anti-fungal effector / Antibiotics / Antifungal activity / Bacteria / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Bacteriology / Bioinformatics / Deoxyribonuclease / Deoxyribonucleases - metabolism / E coli / Fungi / Fungi - metabolism / Gram-negative bacteria / Gram-positive bacteria / Harsh environments / Immunity / interkingdom competition / Nutrients / Pathogens / Plasmids / Polymers / polymicrobial niches / Proteins / Research Article / Toxicity / type VI secretion system / Type VI Secretion Systems - genetics / Type VI Secretion Systems - metabolism / Yeast