Bacterial Competition Systems Share a Domain Required for Inner Membrane Transport of the Bacteriocin Pyocin G from Pseudomonas aeruginosa

Atanaskovic, Iva; Sharp, Connor; Press, Cara; Kaminska, Renata; Kleanthous, Colin

doi:10.1128/mbio.03396-21

Cited by 7 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The predicted structure of the cytotoxic domain shares no similarity with other bacteriocin cytotoxic domains for which the structures are known. The mechanism we propose for pyocin SX1 and SX2 (Figure 7B) is a composite of the findings of this research and current knowledge derived from a variety of bacteriocins including pyocins S2, S5, G and the nuclease-type colicins 11,13,[18][19][20]32,33 . For pyocin SX1 and SX2, the translocation process is initiated by binding of the CPA binding domain to the CPA coli colicins 32,33 .…”

Section: Discussionsupporting

confidence: 57%

“…In the case of the pore-forming pyocin S5, transport to the periplasm is sufficient for the C-terminal cytotoxic domain to insert into and depolarize the inner membrane to kill the cell. For nuclease-type pyocins, an additional inner membrane translocation domain is required to mediate transport to the cytoplasm where its nucleic acid substrate is located (19). For pyocin G, inner membrane translocation has been shown to be dependent on both the AAA + ATPase/protease FtsH and TonB1 (20).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mechanism of targeted killing of P. aeruginosa by pyocins SX1 and SX2

Premsuriya

Mosbahi

Atanaskovic

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Pseudomonas aeruginosa is a common cause of serious hospital-acquired infections, the leading proven cause of mortality in people with cystic fibrosis and is associated with high levels of antimicrobial resistance. Pyocins are narrow spectrum protein antibiotics produced by P. aeruginosa that kill strains of the same species and have the potential to be developed as therapeutics targeting multi-drug resistant isolates. We have identified two novel pyocins designated SX1 and SX2 that show potent killing activity against P. aeruginosa and efficacy in an insect infection model. Pyocin SX1 is a metal-dependent DNase while pyocin SX2 kills cells through inhibition of protein synthesis. Mapping the uptake pathways of SX1 and SX2 shows these pyocins utilize a combination of the common polysaccharide antigen (CPA) and a previously uncharacterized TonB-dependent transporter (TBDT) PA0434 to traverse the outer membrane. In addition, TonB1 and FtsH are required by both pyocins to energise their transport into cells and catalyse their translocation across the inner membrane, respectively. Expression of PA0434 was found to be specifically regulated by copper availability and we have designated PA0434 as Copper Responsive Transporter A, or CrtA. To our knowledge these are the first pyocins described that utilize a TBDT not involved in iron uptake.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Mechanism of targeted killing of P. aeruginosa by pyocins SX1 and SX2

Premsuriya

Mosbahi

Atanaskovic

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, in some instances, this toxin domain is preceded by a Pyocin_S domain, as is the case in VPA1263. Pyocin_S was recently suggested to mediate the transport of DNase toxins across the inner membrane, from the periplasm to the cytoplasm ( 45 ). This activity was shown to be mediated by specific inner membrane proteins that serve as receptors.…”

Section: Discussionmentioning

confidence: 99%

A DNase Type VI Secretion System Effector Requires Its MIX Domain for Secretion

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Interestingly, in some instances this toxin domain is preceded by a Pyocin_S domain, as is the case in VPA1263. Pyocin_S was recently suggested to mediate the transport of DNase toxins across the inner-membrane, from the periplasm to the cytoplasm (Atanaskovic et al , 2022). This activity was shown to be mediated by specific inner-membrane proteins that serve as receptors.…”

Section: Discussionmentioning

confidence: 99%

A DNase T6SS effector requires its MIX domain for secretion

Fridman

Jana

Ben-Yaakov

et al. 2022

Preprint

View full text Add to dashboard Cite

Bacteria use diverse classes of secreted polymorphic toxins to outcompete bacterial rivals. The MIX domain defines a widespread class of polymorphic type VI secretion system (T6SS) effectors, many of which are horizontally shared. Although several MIX-effectors have been investigated, the role of the MIX domain and the activity of many fused toxin domains remain unknown. Here, we use the Vibrio parahaemolyticus MIX-effector VPA1263 to demonstrate that MIX is necessary for T6SS-mediated secretion; however, we find that it is dispensable for interaction with the secreted T6SS tail tube component, VgrG. We also identify a C-terminal HNH nuclease toxin domain in VPA1263, and we demonstrate that it functions as a DNase during interbacterial competition. Finally, we identify variants of the genomic island containing vpa1263 in various vibrios, each carrying a different cargo of antibacterial T6SS effectors or anti-phage defense systems. We propose that these genomic islands are hotspots for bacterial defensive weapons.

show abstract

Bacterial Competition Systems Share a Domain Required for Inner Membrane Transport of the Bacteriocin Pyocin G from Pseudomonas aeruginosa

Abstract: Nuclease bacteriocins are potential antimicrobials for the treatment of antibiotic-resistant bacterial infections. While the mechanism of outer membrane translocation is beginning to be understood, the mechanism of inner membrane transport is not known.

Cited by 7 publications

References 33 publications

Mechanism of targeted killing of P. aeruginosa by pyocins SX1 and SX2

Mechanism of targeted killing of P. aeruginosa by pyocins SX1 and SX2

A DNase Type VI Secretion System Effector Requires Its MIX Domain for Secretion

A DNase T6SS effector requires its MIX domain for secretion

Contact Info

Product

Resources

About