Bacterial multicellular behavior in antiviral defense

Luthe, Tom; Kever, Larissa; Thormann, Kai M.; Frunzke, Julia

doi:10.1016/j.mib.2023.102314

Cited by 15 publications

(6 citation statements)

References 79 publications

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“…It is also interesting to note that some of the findings here are also in contradiction with common perceptions toward certain phage-antibiotic interactions. In particular, while several studies have demonstrated that aminoglycosides and other protein translation inhibitors are antagonistic to the action of the phages due to the inhibition of the synthesis proteins ( 41 , 53 ), here we found that the aminoglycoside AMK synergistically inhibited the growth of the bacteria, with phage, in a concentration-dependent manner ( Fig. 4a ).…”

Section: Discussionsupporting

confidence: 46%

A novel coli myophage and antibiotics synergistically inhibit the growth of the uropathogenic E. coli strain CFT073 in stoichiometric niches

Khunti,

Chantakorn,

Tantibhadrasapa

et al. 2023

Microbiol Spectr

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Urinary tract infections are widespread bacterial infections affecting millions of people annually, with Escherichia coli being the most prevalent. Although phage therapy has recently gained interest as a promising alternative therapy for antibiotic-resistant bacteria, several studies have raised concerns regarding the evolution of phage resistance, making the therapy ineffective. In this study, we discover a novel coli myophage designated as Killian that targets E. coli strains, including the uropathogenic E. coli (UPEC) strain CFT073. It requires at least 20 minutes for 90% of its particles to adsorb to the host cells, undergoes subcellular activities for replication for 30 minutes, and eventually lyses the cells with a burst size of about 139 particles per cell. Additionally, Killian can withstand a wide variety of temperatures (4–50°C) and pHs ( 4 – 10 ). Genome analysis reveals that Killian’s genome consists of 169,905 base pairs with 35.5% GC content, encoding 276 open reading frames; of these, 209 are functionally annotated with no undesirable genes detected, highlighting its potential as an antibiotic alternative against UPEC. However, after an 8-hour phage treatment at high multiplicities of infection, bacterial density continuously increases, indicating an onset of bacterial growth revival. Thus, the combination study between the phage and three different antibiotics, including amikacin, ciprofloxacin, and piperacillin, was performed and showed that certain pairs of phage and antibiotics exhibited synergistic interactions in suppressing the bacterial growth revival. These findings suggest that Killian-antibiotic combinations are effective in inhibiting the growth of UPEC. IMPORTANCE Phage therapy has recently been in the spotlight as a viable alternative therapy for bacterial infections. However, several studies have raised concerns about the emergence of phage resistance that occurs during treatment, making the therapy not much effective. Here, we present the discovery of a novel E. coli myophage that, by itself, can effectively kill the uropathogenic E. coli , but the emergence of bacterial growth revival was detected during the treatment. Phage and antibiotics are then combined to improve the efficiency of the phage in suppressing the bacterial re-growth. This research would pave the way for the future development of phage-antibiotic cocktails for the sustainable use of phages for therapeutic purposes.

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Section: Discussionsupporting

confidence: 46%

A novel coli myophage and antibiotics synergistically inhibit the growth of the uropathogenic E. coli strain CFT073 in stoichiometric niches

Khunti,

Chantakorn,

Tantibhadrasapa

et al. 2023

Microbiol Spectr

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“…Co-cultivations of microorganisms therefore represent a promising approach for the discovery of novel antibiotics otherwise not produced under laboratory conditions 5 . In recent years, also the interaction of Streptomyces with their most abundant predator in the environment – bacteriophages (or phages for short) – increasingly gained attention 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of the newStreptomycesphages Kamino, Geonosis, Abafar and Scarif infecting a broad range of host species

Rackow,

Rolland,

Mohnen

et al. 2024

Preprint

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Streptomyces, a multifaceted genus of soil-dwelling bacteria within the phylum Actinobacteria, features intricate phage-host interactions shaped by its complex life cycle and the synthesis of a diverse array of specialized metabolites. Here, we describe the isolation and characterization of four novelStreptomycesphages infecting a variety of different host species. While phage Kamino, isolated onStreptomyces kasugaensis, is predicted to be temperate and encodes a serine integrase in its genome, phages Geonosis (isolated onS. griseus) and phages Abafar and Scarif, isolated onS. albidoflavus, are virulent phages. Phages Kamino and Geonosis were shown to amplify well in liquid culture leading to a pronounced culture collapse already at low titres. Determination of the host range by testing >40 differentStreptomycesspecies identified phages Kamino, Abafar and Scarif as broad host range phages, with Kamino showing productive infections on 15 different species. Isolated phages were further tested regarding their sensitivity to antiphage molecules. Here, the strongest effects were observed for the DNA-intercalating molecule daunorubicin. Overall, the phages described in this study expand the publicly available portfolio of phages infectingStreptomycesand will be instrumental for advancing the mechanistic understanding of the intricate antiviral strategies employed by these multicellular bacteria.

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“…Recent studies also revealed several mechanisms that are shared among cells within a microbial community. These communal defences encompass the extrusion of membrane vesicles serving as a phage decoy, quorum sensing-based activation of defense systems, biofilm formation and secretion of antiphage small molecules (Luthe et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

“…In-depth analysis of this observation using aminoglycoside-resistant strains revealed a strong inhibition of phage infection by addition of pure apramycin as well culture supernatant (=spent medium) of the natural apramycin producer Streptoalloteichus tenebrarius (Tamura et al, 2008), hinting towards an ecological relevance of such chemically-mediated antiphage defense via aminoglycosides. Their secretion into the environment could create an antiviral microenvironment, thereby providing a chemical defense against phages at the community level (Hardy et al, 2023, Luthe et al, 2023. However, in order to benefit from this, neighboring cells or mycelial structures must possess resistance mechanisms to counteract the antibacterial impact of the compound without abolishing the antiphage effect.…”

Section: Introductionmentioning

confidence: 99%

Decoupling the molecular versatility of aminoglycosides via drug or target modification enables community-wide antiphage defense

Kever,

Zhang,

Hardy

et al. 2024

Preprint

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The ongoing arms race between bacteria and phages has forced bacteria to evolve a sophisticated set of antiphage defense mechanisms that constitute the bacterial immune system. In our previous study, we highlighted the antiphage properties of aminoglycoside antibiotics, which are naturally secreted byStreptomyces. Successful inhibition of phage infection was achieved by addition of pure compounds and supernatants from a natural producer strain highlighting the potential for community-wide antiphage defense. However, given the dual functionality of these compounds, neighboring bacterial cells require resistance to the antibacterial activity of aminoglycosides to benefit from the protection they confer against phages. In this study, we demonstrated the successful uncoupling of antiphage and antibacterial properties via different aminoglycoside-resistance mechanisms encompassing drug and target site modifications. Furthermore, we confirmed the antiphage impact of aminoglycosides in a community context by co-culturing phage-susceptible, apramycin-resistantS. venezuelaewith the apramycin-producing strainStreptoalloteichus tenebrarius. Given the prevalence of aminoglycoside resistance among natural bacterial isolates that allow functional uncoupling of these compounds, this study highlights the ecological relevance of chemical defense via aminoglycosides at the community level.

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Bacterial multicellular behavior in antiviral defense

Cited by 15 publications

References 79 publications

A novel coli myophage and antibiotics synergistically inhibit the growth of the uropathogenic E. coli strain CFT073 in stoichiometric niches

A novel coli myophage and antibiotics synergistically inhibit the growth of the uropathogenic E. coli strain CFT073 in stoichiometric niches

Isolation and characterization of the newStreptomycesphages Kamino, Geonosis, Abafar and Scarif infecting a broad range of host species

Decoupling the molecular versatility of aminoglycosides via drug or target modification enables community-wide antiphage defense

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