Burkholderia cenocepacia utilizes a type VI secretion system for bacterial competition

Abstract

Burkholderia cenocepacia is an opportunistic bacterial pathogen that poses a significant threat to individuals with cystic fibrosis by provoking a strong inflammatory response within the lung. It possesses a type VI secretion system (T6SS), a secretory apparatus that can perforate the cellular membrane of other bacterial species and/or eukaryotic targets, to deliver an arsenal of effector proteins. The B. cenocepacia T6SS (T6SS‐1) has been shown to be implicated in virulence in rats and contributes toward actin rearrangements and inflammasome activation in B. cenocepacia ‐infected macrophages. Here, we present bioinformatics evidence to suggest that T6SS‐1 is the archetype T6SS in the Burkholderia genus. We show that B. cenocepacia T6SS‐1 is active under normal laboratory growth conditions and displays antibacterial activity against other Gram‐negative bacterial species. Moreover, B. cenocepacia T6SS‐1 is not required for virulence in three eukaryotic infection models. Bioinformatics analysis identified several candidate T6SS‐dependent effectors that may play a role in the antibacterial activity of B. cenocepacia T6SS‐1. We conclude that B. cenocepacia T6SS‐1 plays an important role in bacterial competition for this organism, and probably in all Burkholderia species that possess this system, thereby broadening the range of species that utilize the T6SS for this purpose.

Host Adaptation PredisposesPseudomonas aeruginosato Type VI Secretion System-Mediated Predation by theBurkholderia cepaciaComplex

“…In our studies, competition mediated by the T6SS-1 provided strong competitive advantages to three Bcc pathogens (BcAU1054, BmCGD2M, and BdAU0158) against hostadapted P. aeruginosa. Gene clusters encoding the T6SS-1 are prevalent throughout the Bcc (Spiewak et al, 2019), suggesting that T6SS-mediated killing of host-adapted P. aeruginosa may be a common asset of Bcc pathogens. The role of additional T6SSs in Bcc pathogens remains unknown, but it appears that interbacterial antagonism is mostly mediated by the T6SS- There is growing appreciation for the genotypic and phenotypic diversity of P.…”

“…Type VI secretion (T6S) has been studied in the Bcc pathogen Burkholderia cenocepacia strain J2315 (BcJ2315), which produces a T6SS that is important for infection of macrophages and influences the immune response to this pathogen (Aubert et al, 2015;Hunt et al, 2004;Rosales-Reyes et al, 2012). Recent bioinformatic analysis has detected T6SS-encoding genes throughout the Bcc, with one system (referred to as T6SS-1) predominating; however, several species encode multiple T6SSs (Spiewak et al, 2019). The B. cenocepacia strain H111 T6SS was shown to have modest antibacterial activity (Spiewak et al, 2019), though the potential antibacterial role of T6SSs in other Bcc pathogens remains unknown.…”

“…Recent bioinformatic analysis has detected T6SS-encoding genes throughout the Bcc, with one system (referred to as T6SS-1) predominating; however, several species encode multiple T6SSs (Spiewak et al, 2019). The B. cenocepacia strain H111 T6SS was shown to have modest antibacterial activity (Spiewak et al, 2019), though the potential antibacterial role of T6SSs in other Bcc pathogens remains unknown. P. aeruginosa produces three separate T6SSs (the H1-, H2-, and H3-T6SSs), and while both the H1-and H2-T6SSs are antibacterial weapons, the H1-T6SS is the stronger mediator of interbacterial competition (Allsopp et al, 2017;Hood et al, 2010;Russell et al, 2011).…”

Comprehensive genome analysis of a pangolin-associatedParaburkholderia fungorumprovides new insights into its secretion systems and virulence

“…Besides that, we found a T6SS cluster (TssA-TssM) in the pangolin Pf genome, probably playing an important role in bacterial competition (Spiewak et al, 2019).…”

“…This secretion system has emerged as virulence factor that may take part in the pathogenic bacterial-host interactions or promote commensal or mutualistic relationships between bacteria and eukaryotes or to mediate cooperative or competitive interactions between bacteria (Jani & Cotter, 2010). For instance, in Gram-negative bacteria, it has been used for the purpose of interbacterial competition in Bcc member (Spiewak et al, 2019), and endure the innate immune response in host (Lennings, West & Schwarz, 2019). We also identified several regulatory genes that form the major requirement for a functional T6SS, such as structural proteins (VasH, VasK, VasF, VasA), effector protein (VgrG), and functional domains (chaperone ClpB, ImpA, ImpB, ImpC, ImpD, ImpF, ImpG, ImpH, ImpJ) in the pangolin Pf genome.…”