O serotype‐independent susceptibility of
            <i>Pseudomonas aeruginosa</i>
            to lectin‐like pyocins

Ghequire, Maarten G. K.; Dingemans, Jozef; Pirnay, Jean‐Paul; Vos, Daniël De; Cornélis, Pierre; Mot, René De

doi:10.1002/mbo3.210

Cited by 19 publications

(27 citation statements)

References 25 publications

(49 reference statements)

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“…To further explore this potential targeting of BamA by use of a different indicator strain-bacteriocin combination, a similar experimental setup was applied to P. aeruginosa PAO1, which is susceptible to PyoL1 of P. aeruginosa C1433 (22,24), a lectin-like bacteriocin sharing only 32% amino acid identity with LlpA1. A set of spontaneous mutants growing inside halos was randomly selected (1 mutant per halo; 30 independent cultures), validated for altered PyoL1 susceptibility, and their ␤-barrel bamA gene fragments were sequenced.…”

Section: Resultsmentioning

confidence: 99%

“…Compared to B-lectins from plants, the affinity of Pseudomonas LlpAs for D-mannose is low, reflecting a much higher affinity of the bacteriocin for D-rhamnose (22), a 6-deoxymannose that is omnipresent in the common polysaccharide antigen (CPA) of Pseudomonas lipopolysaccharide (LPS) (23). No association between LlpA selectivity and O serotype of target cells could be detected for lectin-like bacteriocins from Pseudomonas aeruginosa (also designated L-type pyocins) (24). CPA binding capacity is hosted by the carboxy-terminal lectin domain; however, lack of LPS binding is not sufficient for provoking full LlpA resistance toward susceptible strains (22).…”

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confidence: 99%

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Hitting with a BAM: Selective Killing by Lectin-Like Bacteriocins

Ghequire

Swings

Michiels

et al. 2018

mBio

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Lectin-like bacteriocins (LlpAs) are secreted by proteobacteria and selectively kill strains of their own or related species, and they are composed of two B-lectin domains with divergent sequences. In spp., initial binding of these antibacterial proteins to cells is mediated by the carboxy-terminal domain through d-rhamnose residues present in the common polysaccharide antigen of their lipopolysaccharide, whereas the amino-terminal domain accounts for strain selectivity of killing. Here, we show that spontaneous LlpA-resistant mutants carry mutations in one of three surface-exposed moieties of the essential β-barrel outer membrane protein insertase BamA, the core component of the BAM complex. Polymorphism of this loop in different groups is linked to LlpA susceptibility, and targeted cells all share the same signature motif in this loop. Since heterologous expression of such a gene confers LlpA susceptibility upon a resistant strain, BamA represents the primary bacteriocin selectivity determinant in pseudomonads. Contrary to modular bacteriocins that require uptake via the Tol or Ton system, parasitism of BamA as an LlpA receptor advocates a novel bacteriocin killing mechanism initiated by impairment of the BAM machinery. Bacteria secrete a variety of molecules to eliminate microbial rivals. Bacteriocins are a pivotal group of peptides and proteins that assist in this fight, specifically killing related bacteria. In Gram-negative bacteria, these antibacterial proteins often comprise distinct domains for initial binding to a target cell's surface and subsequent killing via enzymatic or pore-forming activity. Here, we show that lectin-like bacteriocins, a family of bacteriocins that lack the prototypical modular toxin architecture, also stand out by parasitizing BamA, the core component of the outer membrane protein assembly machinery. A particular surface-exposed loop of BamA, critical for its function, serves as a key discriminant for cellular recognition, and polymorphisms in this loop determine whether a strain is susceptible or immune to a particular bacteriocin. These findings suggest a novel mechanism of contact-dependent killing that does not require cellular uptake. The evolutionary advantage of piracy of an essential cellular compound is highlighted by the observation that contact-dependent growth inhibition, a distinct antagonistic system, can equally take advantage of this receptor.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Hitting with a BAM: Selective Killing by Lectin-Like Bacteriocins

Ghequire

Swings

Michiels

et al. 2018

mBio

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“…85 One class of such bacteriocins are the LlpA bacteriocins, which are produced by several bacterial species including the pseudomonads: P. putida, P. protegens, and P. syringae , the plant pathogen Xanthomonas citri , and the human pathogen Burkholderia cenocepacia. 86 LlpA bacteriocins such as Pyocin L1 (PyoL1) display high affinity for D-rhamnose, which is a constituent of the common polysaccharide antigen (CPA) found in the P. aeruginosa cell membrane, accounting for the specificity exhibited by this bacteriocin. PyoL1 displayed antibacterial activity against a majority of P. aeruginosa isolates tested, and displayed no activity against other Pseudomonads.…”

Section: Identification Of Narrow-spectrum Antibacterial Agentsmentioning

confidence: 99%

“…PyoL1 displayed antibacterial activity against a majority of P. aeruginosa isolates tested, and displayed no activity against other Pseudomonads. 86 Another pyoicn, pyocin S5 was reported to exhibit antibacterial activity against several P. aeruginosa strains, and was inactive against E. coli and S. aureus even at concentrations of up to 2.16 mg/mL. 87 …”

Section: Identification Of Narrow-spectrum Antibacterial Agentsmentioning

confidence: 99%

Narrow-spectrum antibacterial agents

2018

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While broad spectrum antibiotics play an invaluable role in the treatment of bacterial infections, there are some drawbacks to their use, namely selection for and spread of resistance across multiple bacterial species, and the detrimental effect they can have upon the host microbiome. If the causitive agent of the infection is known, the use of narrow-spectrum antibacterial agents has the potential to mitigate some of these issues. This review outlines the advantages and challenges of narrow-spectrum antibacterial agents, discusses the progress that has been made toward developing diagnostics to enable their use, and describes some of the narrow-spectrum antibacterial agents currently being investigated against some of the most clinically important bacteria including Clostridium difficile, Mycobacterium tuberculosis and several ESKAPE pathogens.

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“…L‐type pyocins host two monocot mannose‐binding lectin domains, one of which is involved in binding the pseudomonad common polyantigen, and kill target cells via an unknown mechanism (Ghequire et al. , ; McCaughey et al. ).…”

Section: Introductionmentioning

confidence: 99%

Identification and functional analysis of a bacteriocin, pyocin S6, with ribonuclease activity from a Pseudomonas aeruginosa cystic fibrosis clinical isolate

et al. 2016

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S‐type pyocins are bacteriocins produced by Pseudomonas aeruginosa isolates to antagonize or kill other strains of the same species. They have a modular organization comprising a receptor‐binding domain recognizing a surface constituent of the target bacterium, a domain for translocation through the periplasm, and a killing or toxic domain with DNase, tRNase, or pore‐forming activity. Pyocins S2, S3, S4, and S5 recognize TonB‐dependent ferri‐siderophore receptors in the outer membrane. We here describe a new nuclease bacteriocin, pyocin S6, encoded in the genome of a P. aeruginosa cystic fibrosis (CF) clinical isolate, CF_PA39. Similarly to pyocins S1 and S2, the S6 toxin–immunity gene tandem was recruited to the genomic region encoding exotoxin A. The pyocin S6 receptor‐binding and translocation domains are identical to those of pyocin S1, whereas the killing domain is similar to the 16S ribonuclease domain of Escherichia coli colicin E3. The cytotoxic activity was abolished in pyocin S6 forms with a mutation in the colicin E3‐equivalent catalytic motif. The CF_PA39 S6 immunity gene displays a higher expression level than the gene encoding the killing protein, the latter being only detected when bacteria are grown under iron‐limiting conditions. In the S1‐pyocinogenic strain P. aeruginosa ATCC 25324 and pyocin S2 producer P. aeruginosa PAO1, a remnant of the pyocin S6 killing domain and an intact S6‐type immunity gene are located downstream of their respective pyocin operons. Strain PAO1 is insensitive for pyocin S6, and its S6‐type immunity gene provides protection against pyocin S6 activity. Purified pyocin S6 inhibits one‐fifth of 110 P. aeruginosa CF clinical isolates tested, showing clearer inhibition zones when the target cells are grown under iron limitation. In this panel, about half of the CF clinical isolates were found to host the S6 genes. The pyocin S6 locus is also present in the genome of some non‐CF clinical isolates.

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O serotype‐independent susceptibility of Pseudomonas aeruginosa to lectin‐like pyocins

Cited by 19 publications

References 25 publications

Hitting with a BAM: Selective Killing by Lectin-Like Bacteriocins

Hitting with a BAM: Selective Killing by Lectin-Like Bacteriocins

Narrow-spectrum antibacterial agents

Identification and functional analysis of a bacteriocin, pyocin S6, with ribonuclease activity from a Pseudomonas aeruginosa cystic fibrosis clinical isolate

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