Abstract
ABSTRACTModular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently inhibit the toxin’s activity through formation of bacteriocin-immunity complexes or by insertion in the inner membrane, depending on the type of toxin module. We demonstrate strain-specific inhibitory activity for PmnH, a Pseudomonas bacteriocin with an unprecedented dual-toxin architecture, hosting both a colicin M domain, potentially interfering with peptidoglycan synthesis, and a novel colicin N-type domain, a pore-forming module distinct from the colicin Ia-type domain in Pseudomonas aeruginosa pyocin S5. A downstream-linked gene product confers PmnH immunity upon susceptible strains. This protein, ImnH, has a transmembrane topology similar to that of Pseudomonas colicin M-like and pore-forming immunity proteins, although homology with either of these is essentially absent. The enhanced killing activity of PmnH under iron-limited growth conditions reflects parasitism of the ferrichrome-type transporter for entry into target cells, a strategy shown here to be used as well by monodomain colicin M-like bacteriocins from pseudomonads. The integration of a second type of toxin module in a bacteriocin gene could offer a competitive advantage against bacteria displaying immunity against only one of both toxic activities.
Highlights
Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria
Another hybrid organization, comprising two apparently unrelated modules, is found in PmnH, joining a colicin M (ColM) domain (Pfam PF14859) to a pore-forming domain (Pfam PF01024) (Fig. 1A) [24]. This pore-forming domain is phylogenetically distinct from the domain in pyocin S5 (PyoS5) (Fig. 1B; see Fig. S1 in the supplemental material): the latter domain is more closely related to colicin Ia (ColIa) [25], whereas PmnH’s C-terminal domain belongs to a clade with colicin N (ColN) [26, 27], sharing 44.6% and 33.5% amino acid identity to the corresponding colicin domains, respectively
In light of (i) the structural similarities observed between the amino-terminal domains of pseudomonads are M-type bacteriocins (PseuMs) and colicin M and (ii) the homology between the aminoterminal domains of PmnH and previously characterized PseuMs from P. aeruginosa NCTC10332, P. fluorescens Q8r1-96, and P. syringae pv. tomato DC3000 (Fig. S3), we examined the possibility that FiuA may be parasitized by PseuM bacteriocins as well
Summary
Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Together with the multisubunit cell-perforating tailocins [8], S-type bacteriocins constitute a very abundant group in Pseudomonas genomes [3] These modular polypeptides resemble the colicins from Escherichia coli [9] and share a general organization that includes a domain for target cell attachment, a domain mediating subsequent translocation, and a carboxy-terminal toxin domain. In contrast to other immunity proteins protecting from enzymatic toxin domains, PmiA proteins display very poor sequence homology with the exception of a short semiconserved periplasmic motif, whose role in the PseuM immunity mechanism remains elusive at this point
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