Localized recombination drives diversification of killing spectra for phage-derived syringacins

Baltrus, David A.; Clark, Meara; Smith, Caitlin; Hockett, Kevin L.

doi:10.1038/s41396-018-0261-3

Cited by 22 publications

(52 citation statements)

References 44 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tailocin target specificity is defined by its receptor-binding proteins (RBPs): tail fibers, tail spikes, and tail tips [3]. Recent studies have indicated that the RBPs are modular: they naturally undergo localized recombination [4], and they can be swapped in and out manually to engineer target specificity [5][6][7][8]. Following recognition and binding, tailocins kill target cells with very high potency, with one to a few particles sufficient for killing a sensitive cell [5,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins

et al. 2021

View full text Add to dashboard Cite

Tailocins are bactericidal protein complexes produced by a wide variety of bacteria that kill closely related strains and may play a role in microbial community structure. Thanks to their high specificity, tailocins have been proposed as precision antibacterial agents for therapeutic applications. Compared to tailed phages, with whom they share an evolutionary and morphological relationship, bacterially produced tailocins kill their host upon production but producing strains display resistance to self-intoxication. Though lipopolysaccharide (LPS) has been shown to act as a receptor for tailocins, the breadth of factors involved in tailocin sensitivity, and the mechanisms behind resistance to self-intoxication, remain unclear. Here, we employed genome-wide screens in four non-model pseudomonads to identify mutants with altered fitness in the presence of tailocins produced by closely related pseudomonads. Our mutant screens identified O-antigen composition and display as most important in defining sensitivity to our tailocins. In addition, the screens suggest LPS thinning as a mechanism by which resistant strains can become more sensitive to tailocins. We validate many of these novel findings, and extend these observations of tailocin sensitivity to 130 genome-sequenced pseudomonads. This work offers insights into tailocin–bacteria interactions, informing the potential use of tailocins in microbiome manipulation and antibacterial therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This likely reflects the different environmental niches that P. aeruginosa and P. syringae occupy. Intriguingly, diversification and expansion of the tailocin family in P. syringae is driven by localized recombination of tailocin genes like those encoding the tail fibers (Baltrus et al, 2019).…”

Section: Tailocinsmentioning

confidence: 99%

“…Similarly, for CLBs appropriate domain swapping could yield chimeric bacteriocins for which there is no immunity protein-based resistance in the targeted bacterial species (Akutsu et al, 1989). For tailocins, the exchange of tail fibers has already been shown to produce novel chimeras (Baltrus et al, 2019).…”

Section: Applications Of Bacteriocins and Future Perspectivesmentioning

confidence: 99%

Bacteriocins Targeting Gram-Negative Phytopathogenic Bacteria: Plantibiotics of the Future

et al. 2020

View full text Add to dashboard Cite

Gram-negative phytopathogenic bacteria are a significant threat to food crops. These microbial invaders are responsible for a plethora of plant diseases and can be responsible for devastating losses in crops such as tomatoes, peppers, potatoes, olives, and rice. Current disease management strategies to mitigate yield losses involve the application of chemicals which are often harmful to both human health and the environment. Bacteriocins are small proteinaceous antibiotics produced by bacteria to kill closely related bacteria and thereby establish dominance within a niche. They potentially represent a safer alternative to chemicals when used in the field. Bacteriocins typically show a high degree of selectivity toward their targets with no off-target effects. This review outlines the current state of research on bacteriocins active against Gramnegative phytopathogenic bacteria. Furthermore, we will examine the feasibility of weaponizing bacteriocins for use as a treatment for bacterial plant diseases.

show abstract

“…A wide body of evidence shows that tailocin-producing strains are resistant to the tailocins they produce 5,13 , in a phenotype referred to as resistance to self-intoxication ( Fig. 3A, Fig.…”

Section: Disruption Of Genes Encoding Outer Membrane Lipid Asymmetry mentioning

confidence: 99%

“…Tailocin target specificity is defined by its receptor-binding proteins (RBPs): tail fibers, tail spikes and tail tips 4 . Recent studies have indicated that the RBPs are modular: they naturally undergo localized recombination 5 , and they can be swapped in and out manually to engineer target specificity [6][7][8][9] . Following recognition and binding, tailocins kill target cells with very high potency, with one to a few particles sufficient for killing a sensitive cell 6,10-12 .…”

Section: Introductionmentioning

confidence: 99%

Systematic Discovery of Pseudomonad Genetic Factors Involved in Sensitivity to Tailocins

Carim

Azadeh

Kazakov

et al. 2020

Preprint

View full text Add to dashboard Cite

Tailocins are bactericidal protein complexes produced by a wide variety of bacteria to compete against closely related strains. Like tailed bacteriophages, with whom they share an evolutionary and morphological relationship, tailocins bind and kill a narrow spectrum of target cells. Thanks to their high specificity, tailocins have garnered recent attention for their potential as precision antibacterial agents. Nevertheless, the field currently lacks a systematic investigation of genetic determinants of tailocin sensitivity. Here, we employed barcoded transposon-insertion mutant libraries and comparative genomics to assess genetic contributions to tailocin sensitivity in pseudomonads. Our mutant screens identified O-specific antigen (OSA) composition and display as most important in defining sensitivity to our tailocins. Additionally, the screens suggest lipopolysaccharide (LPS) thinning as a mechanism by which resistant strains can become more sensitive to tailocins. Our comparative genomics analyses show a loose relationship between OSA biosynthetic genes and tailocin sensitivity, as well as sensitivity nuances that require further investigation. Overall, our data reinforces the model that LPS molecules can act as either a receptor for, or shield against, tailocin binding and killing. This work offers insight into the specificity of tailocins and tailocin-mediated competition, informing the potential use of tailocins in microbiome manipulation and antibacterial therapy.

show abstract

Localized recombination drives diversification of killing spectra for phage-derived syringacins

Cited by 22 publications

References 44 publications

Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins

Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins

Bacteriocins Targeting Gram-Negative Phytopathogenic Bacteria: Plantibiotics of the Future

Systematic Discovery of Pseudomonad Genetic Factors Involved in Sensitivity to Tailocins

Contact Info

Product

Resources

About