Pyocin

{{Short description|Type of bacteriocin}} '''Pyocins''' are [[bacteriocin]]s produced by [[bacteria]] belonging to the ''[[Pseudomonas]]'' genus.<ref name=":2">{{Cite journal |last1=Estrada |first1=Isaac |last2=Smith |first2=Parker |last3=Mei |first3=Madeline |last4=Goldberg |first4=Joanna B. |last5=Diggle |first5=Stephen P. |date=2025 |title=Microbial Primer: The R-pyocins of Pseudomonas aeruginosa |journal=Microbiology |volume=171 |issue=12 |pages=001640 |doi=10.1099/mic.0.001640 |pmid=41370006 |doi-access=free |issn=1465-2080}}</ref><ref name=":1">{{Cite journal|title=R-pyocins as targeted antimicrobials against Pseudomonas aeruginosa|journal=npj Antimicrobials and Resistance|date=2025-02-28|issn=2731-8745|pages=17|volume=3|issue=1|doi=10.1038/s44259-025-00088-1|language=en|first1=Madeline|last1=Mei|first2=Isaac|last2=Estrada|first3=Stephen P.|last3=Diggle|first4=Joanna B.|last4=Goldberg |pmid=40021925 |pmc=11871291 }}</ref> [[François Jacob]] described the first pyocin in 1954.<ref>{{Cite journal|last=Jacob|first=Francois|title=Biosynthèse induite et mode d'action d'une pyocine, antibiotique de Pseudomonas pyocyanea|journal=Ann. Inst. Pasteur|volume=86|pages=149–160}}</ref> Pyocins can be divided into three distinct classes: S-type, R-type, and F-type pyocins. S-type pyocins are [[colicin]]-like bacteriocins and R-type and F-type pyocins belong to tailocins.<ref name=":0">{{Cite journal|last1=Ghequire|first1=Maarten G.K.|last2=De Mot|first2=René|date=July 2014|title=Ribosomally encoded antibacterial proteins and peptides from Pseudomonas|journal=FEMS Microbiology Reviews|language=en|volume=38|issue=4|pages=523–568|doi=10.1111/1574-6976.12079|pmid=24923764|bibcode=2014FEMMR..38..523G |issn=1574-6976|doi-access=free}}</ref>

== R-type and F-type pyocins == R- and F-type pyocins have mainly been investigated in ''[[Pseudomonas aeruginosa]]''.<ref>{{Cite journal|title=Microbe Profile: Pseudomonas aeruginosa: opportunistic pathogen and lab rat|journal=Microbiology|date=2020|issn=1465-2080|pages=30–33|volume=166|issue=1|doi=10.1099/mic.0.000860|first1=Stephen P.|last1=Diggle|author2-link=Marvin Whiteley|first2=Marvin|last2=Whiteley |pmid=31597590 |pmc=7273324 |doi-access=free }}</ref> These two types differ by their structure; they are both composed of a sheath and a hollow tube forming a long helicoidal hexameric structure attached to a baseplate.<ref name=":2" /><ref name=":1" /> There are multiple tail fibers that allow the particle to bind to the target cell. However, the R-pyocins are a large, rigid contractile tail-like structure whereas the F-pyocins are small flexible, non-contractile tail-like structures.<ref name=":1" /><ref name=":0" /> The F-type pyocins described so far are pyocin 28, 430f, F1, F2, and F3.<ref name=":0" />

R-pyocins are known for their distinctive structure, which resembles the contractile tail of a [[Myoviridae]] [[bacteriophage]], but they lack the DNA-containing capsid head. This non-replicative nature offers advantages over [[phage therapy]], such as predictable dosing and the inability to facilitate [[horizontal gene transfer]] of [[virulence]] or antibiotic resistance genes.<ref name=":1" />

The killing mechanism of R-pyocins is highly targeted and involves several steps:

* Receptor Binding: The R-pyocin tail fibers recognize and bind to specific monosaccharide residues in the outer core oligosaccharide of the target bacterium's [[lipopolysaccharide]] (LPS), which decorates the outer membrane. The LPS acts as both the receptor and, potentially, a shield. * Contraction and Puncture: Upon binding, the baseplate undergoes a conformational change that triggers the sheath to contract. The contraction drives the inner tube and tail spike to puncture the outer membrane of the target cell. * Cell Death: This interaction is thought to form an ion-conducting channel that rapidly dissipates the cell's proton motive force, leading to membrane depolarization and ultimately cell death.

R-pyocins are categorized into five subtypes (R1-R5), distinguished by the specificity of their tail fiber for different LPS receptors.<ref name=":2" /><ref name=":1" /> Subtypes are often grouped together as a single functional subtype due to high sequence similarity in their variable C-terminal tail fiber regions. Studies have shown that a high frequency of ''P. aeruginosa'' strains isolated from [[cystic fibrosis]] (CF) lung infections are susceptible to R2-pyocins, supporting their potential as therapeutic agents.<ref>{{Cite journal|title=Heterogenous Susceptibility to R-Pyocins in Populations of Pseudomonas aeruginosa Sourced from Cystic Fibrosis Lungs|journal=mBio|date=2021-05-04|pages=10.1128/mbio.00458–21|volume=12|issue=3|doi=10.1128/mbio.00458-21|doi-access=free|first1=Madeline|last1=Mei|first2=Jacob|last2=Thomas|first3=Stephen P.|last3=Diggle |pmid=33947755 |pmc=8262887 }}</ref><ref>{{Cite journal|title=High prevalence of lipopolysaccharide mutants and R2-pyocin susceptible variants in Pseudomonas aeruginosa populations sourced from cystic fibrosis lung infections|journal=Microbiology Spectrum|date=2023-10-25|pages=e01773–23|volume=11|issue=6|doi=10.1128/spectrum.01773-23|doi-access=free|first1=Madeline|last1=Mei|first2=Preston|last2=Pheng|first3=Detriana|last3=Kurzeja-Edwards|first4=Stephen P.|last4=Diggle |pmid=37877708 |pmc=10714928 }}</ref> Further, R-pyocins have also been shown to be effective at clearing ''P. aeruginosa'' [[Biofilm|biofilms]].<ref>{{Cite journal|title=Competition in Biofilms between Cystic Fibrosis Isolates of Pseudomonas aeruginosa Is Shaped by R-Pyocins|journal=mBio|date=2019-01-29|pages=10.1128/mbio.01828–18|volume=10|issue=1|doi=10.1128/mbio.01828-18|doi-access=free|first1=Olubukola|last1=Oluyombo|first2=Christopher N.|last2=Penfold|first3=Stephen P.|last3=Diggle |pmid=30696740 |pmc=6355985 }}</ref>

== S-type pyocins == S-type (soluble) pyocins are binary protein complexes that compose of a cytotoxic protein and an immunity protein that protects the producing strain from cytotoxic effects. The amino-terminal domain of the protein takes part in receptor binding as the carboxy-terminal domain is responsible for cytotoxic effect. Most S-type pyocins act by degrading DNA and RNA but some exhibit their cytotoxicity by forming pores to cell surface or by lipid degradation. Several S-type pyocins have been found so far: S1, S2, AP41, S3, S4, S5, S6.<ref name=":0" />

Pyocin G is an example of a novel S1-type nuclease pyocin. It binds to hemin uptake receptor Hur on target cell surface and translocates to the cytoplasm where it degrades DNA. Pyocin G uses inner membrane proteins TonB1 and FtsH for translocation. Pyocin G is highly active against ''P. aeruginosa'' clinical isolates ''in vitro'' as well as ''in vivo'' and could be active in ''P.aeruginosa'' infections also in humans<ref>{{Cite journal|last1=Atanaskovic|first1=Iva|last2=Mosbahi|first2=Khedidja|last3=Sharp|first3=Connor|last4=Housden|first4=Nicholas G.|last5=Kaminska|first5=Renata|last6=Walker|first6=Daniel|last7=Kleanthous|first7=Colin|date=June 2020|title=Targeted Killing of Pseudomonas aeruginosa by Pyocin G Occurs via the Hemin Transporter Hur|journal=Journal of Molecular Biology|language=en|volume=432|issue=13|pages=3869–3880|doi=10.1016/j.jmb.2020.04.020|pmc=7322526|pmid=32339530}}</ref>

In silico methods are revealing also new types of S-pyocins when large databases of sequenced DNA from ''Pseudomonas''-genus are being screened for new pyocin coding sequences.<ref name=":0" />

== References == {{reflist}} [[Category:Bacteriocins]] [[Category:Bactericides]] [[Category:Bacterial toxins]] [[Category:Antimicrobial peptides]]