H3-T6SS of Pseudomonas aeruginosa PA14 contributes to environmental adaptation via secretion of a biofilm-promoting effector

Abstract

Microbial species often occur in complex communities and exhibit intricate synergistic and antagonistic interactions. To avoid predation and compete for favorable niches, bacteria have evolved specialized protein secretion systems. The type VI secretion system (T6SS) is a versatile secretion system widely distributed among Gram-negative bacteria that translocates effectors into target cells or the extracellular milieu via various physiological processes. Pseudomonas aeruginosa is an opportunistic pathogen responsible for many diseases, and it has three independent T6SSs (H1-, H2-, and H3-T6SS). In this study, we found that the H3-T6SS of highly virulent P. aeruginosa PA14 is negatively regulated by OxyR and OmpR, which are global regulatory proteins of bacterial oxidative and acid stress. In addition, we identified a H3-T6SS effector PA14_33970, which is located upstream of VgrG3. PA14_33970 interacted directly with VgrG3 and translocated into host cells. Moreover, we found that H3-T6SS and PA14_33970 play crucial roles in oxidative, acid, and osmotic stress resistance, as well as in motility and biofilm formation. PA14_33970 was identified as a new T6SS effector promoting biofilm formation and thus named TepB. Furthermore, we found that TepB contributes to the virulence of P. aeruginosa PA14 toward Caenorhabditis elegans. Overall, our study indicates that H3-T6SS and its biofilm-promoting effector TepB are regulated by OxyR and OmpR, both of which are important for adaptation of P. aeruginosa PA14 to multiple stressors, providing insights into the regulatory mechanisms and roles of T6SSs in P. aeruginosa.

The role of the type VI secretion system in the stress resistance of plant-associated bacteria

“…This may be a general strategy for pathogens to resist acidic conditions (Zhang et al 2013 ). Alternatively, H3-T6SS, which is negatively regulated by OmpR in P. aeruginosa , and its secreted effector protein TepB, were able to aid in bacterial survival under acidic conditions (Yang et al 2022b ).…”

Killing in the name of: T6SS structure and effector diversity

“…Additionally, recent studies have shown effectors that promote biofilm formation, along with proteins encoded within T6SS clusters that mediate adhesion. These proteins may not necessarily be secreted by the T6SS but can still alter the behaviour of T6SS + bacteria [88,89]. These functions benefit T6SS-harbouring organisms by enhancing the effectiveness of the contact-dependent T6 system or by facilitating communication between bacteria that could result in beneficial group behaviours such as protection from predation.…”

“… P. aeruginosa TepB effector, T 6SS e ffector p romoting b iofilm formation, is involved in the manipulation of bacterial behaviour [89]. This effector is delivered by P.…”

“… P. aeruginosa TepB effector, T 6SS e ffector p romoting b iofilm formation, is involved in the manipulation of bacterial behaviour [ 89 ]. This effector is delivered by P. aeruginosa H3-T6SS and is responsible for three different phenotypes, namely biofilm formation, motility and stress resistance.…”

“…This effector is delivered by P. aeruginosa H3-T6SS and is responsible for three different phenotypes, namely biofilm formation, motility and stress resistance. Indeed, deletion of tepB results in reduced biofilm growth, diminished swimming and swarming motility and attenuated resistance to oxidative, osmotic and acid stresses [ 89 ]. This suggests that TepB acts as an inter-microbial signal effector, a role for a T6SS effector that has only been suggested for the T6SS but elegantly demonstrated for other competition systems such as the T5SS CDI systems [ 120 ].…”