Abstract
Klebsiella pneumoniae is recognized as an urgent threat to human health due to the increasing isolation of multidrug resistant strains. Hypervirulent strains are a major concern due to their ability to cause life-threating infections in healthy hosts. The type VI secretion system (T6SS) is widely implicated in microbial antagonism, and it mediates interactions with host eukaryotic cells in some cases. In silico search for genes orthologous to T6SS component genes and T6SS effector genes across 700 K. pneumoniae genomes shows extensive diversity in T6SS genes across the K. pneumoniae species. Temperature, oxygen tension, pH, osmolarity, iron levels, and NaCl regulate the expression of the T6SS encoded by a hypervirulent K. pneumoniae strain. Polymyxins and human defensin 3 also increase the activity of the T6SS. A screen for regulators governing T6SS uncover the correlation between the transcription of the T6SS and the ability to kill E. coli prey. Whereas H-NS represses the T6SS, PhoPQ, PmrAB, Hfq, Fur, RpoS and RpoN positively regulate the T6SS. K. pneumoniae T6SS mediates intra and inter species bacterial competition. This antagonism is only evident when the prey possesses an active T6SS. The PhoPQ two component system governs the activation of K. pneumoniae T6SS in bacterial competitions. Mechanistically, PhoQ periplasmic domain, and the acid patch within, is essential to activate K. pneumoniae T6SS. Klebsiella T6SS also mediates anti-fungal competition. We have delineated the contribution of each of the individual VgrGs in microbial competition and identified VgrG4 as a T6SS effector. The DUF2345 domain of VgrG4 is sufficient to intoxicate bacteria and yeast. ROS generation mediates the antibacterial effects of VgrG4, and the antitoxin Sel1E protects against the toxic activity of VgrG4. Our findings provide a better understanding of the regulation of the T6SS in bacterial competitions, and place ROS as an early event in microbial competition.
Highlights
The type VI secretion system (T6SS) is a bacterial nanomachinery that delivers substrates into a target cell in a one-step process
We demonstrate that Klebsiella exploits the type VI secretion system (T6SS) nanoweapon to kill bacterial competitors and fungi
We identified one of the toxins deployed by the T6SS to antagonize other microbes and revealed how Klebsiella protects itself from this toxin
Summary
The type VI secretion system (T6SS) is a bacterial nanomachinery that delivers substrates into a target cell in a one-step process. Rao and co-workers identified the T6SS of Edwardsiella tarda in a mass spectrometric screen for secreted virulence factors [2]. Initial studies reported that T6SSs contributed to virulence and/or interaction with eukaryotic cells in multiple bacterial species, primarily pathogens (Vibrio cholerae, Burkholderia ssp., Pseudomonas aeruginosa, E. tarda, Salmonella gallinarum) [3,4,5,6]. The first antibacterial T6SS was described in P. aeruginosa in 2010 [7], and since the T6SS has been implicated in efficient killing of competitors, quorum sensing and horizontal gene transfer [8,9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
