Abstract
The type VI secretion system (T6SS) is widely distributed in Gram-negative bacteria, whose function is known to translocate substrates to eukaryotic and prokaryotic target cells to cause host damage or as a weapon for interbacterial competition. Pseudomonas aeruginosa encodes three distinct T6SS clusters (H1-, H2-, and H3-T6SS). The H1-T6SS-dependent substrates have been identified and well characterized; however, only limited information is available for the H2- and H3-T6SSs since relatively fewer substrates for them have yet been established. Here, we obtained P. aeruginosa H2-T6SS-dependent secretomes and further characterized the H2-T6SS-dependent copper (Cu2+)-binding effector azurin (Azu). Our data showed that both azu and H2-T6SS were repressed by CueR and were induced by low concentrations of Cu2+. We also identified the Azu-interacting partner OprC, a Cu2+-specific TonB-dependent outer membrane transporter. Similar to H2-T6SS genes and azu, expression of oprC was directly regulated by CueR and was induced by low Cu2+. In addition, the Azu-OprC-mediated Cu2+ transport system is critical for P. aeruginosa cells in bacterial competition and virulence. Our findings provide insights for understanding the diverse functions of T6SSs and the role of metal ions for P. aeruginosa in bacteria-bacteria competition.
Highlights
Copper (Cu) is an indispensable metal ion that plays a crucial role in the development of almost all aspects of mammalian physiology; defects in Cu homeostasis impact everything from immune responses to microbial infection [1, 2]
T6SS plays an important role in anti-bacterial competition or delivers effector proteins to both eukaryotic and prokaryotic cells
We report a Cu2+-scavenging pathway consisting of a copper transporter, OprC, and a type VI secretion system (H2-T6SS)
Summary
Copper (Cu) is an indispensable metal ion that plays a crucial role in the development of almost all aspects of mammalian physiology; defects in Cu homeostasis impact everything from immune responses to microbial infection [1, 2]. Given the essential role of Cu in bacterial physiology, it is not surprising that restriction of this micronutrient is an important innate defense strategy [4]. Azurin (Azu) is a high affinity of oxidized copper (Cu2+)-bound protein [10], which coordinates the activity of respiratory metalloenzymes as cofactors by copper uptake in Pseudomonas aeruginosa [11]. Insights into the mechanisms of metal regulation and transport have been achieved, little is known on the importance of Cu2+ availability in bacterial pathogenesis
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