Evaluating efficacy of bacteriophage therapy against<i>Staphylococcus aureus</i>infections using a silkworm larval infection model

Takemura‐Uchiyama, Iyo; Uchiyama, Jumpei; Kato, Shin; Inoue, Tetsuyoshi; Ujihara, Takako; Ohara, Naoya; Daibata, Masanori; Matsuzaki, Shigenobu

doi:10.1111/1574-6968.12220

Cited by 42 publications

(37 citation statements)

References 23 publications

(29 reference statements)

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“…Using two new phages to infect the bacterium, we found no adverse effects on the silkworm, but the phages did destroy the bacteria cells 3 . Our results using silkworm larvae were similar to those using these phages against S. aureus infections in mice.…”

Section: The Silk Roadmentioning

confidence: 88%

Perspective: The age of the phage

Matsuzaki

Uchiyama

Takemura‐Uchiyama

et al. 2014

Nature

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Section: The Silk Roadmentioning

confidence: 88%

Perspective: The age of the phage

Matsuzaki

Uchiyama

Takemura‐Uchiyama

et al. 2014

Nature

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“…The transduction activities of other phages are also of interest in staphylococci. Thus, we examined the generalized transduction activity and host range using three types of staphylococcal phages: siphophages fMR25 and 80, podophage S13 0 and myophage S25-3 Hoshiba et al, 2010;Takemura-Uchiyama et al, 2013) (Supplementary Table S2). Phages 80 and fMR25 were S. aureusspecific phages that exhibited transduction activities in S. aureus (Supplementary Table S1 and Supplementary Figure S4).…”

Section: Generalized Transduction In Staphylococcus Sppmentioning

confidence: 99%

“…Electron microscopy, genome size estimation and nucleoside analysis were conducted to characterize the phage, according to published methods (Uchiyama et al, 2008(Uchiyama et al, , 2012Takemura-Uchiyama et al, 2013). Phage S6 was shown to belong to the family Myoviridae with a genome size of ca.…”

mentioning

confidence: 99%

“…Uracil was used as a nucleic acid base instead of thymine in the DNA of phage S6 (Supplementary Figure S1). Tests of the host range using a published procedure (Takemura- Uchiyama et al, 2013) demonstrated that phage S6 exhibited lysis-from-without and/or plaque-forming activities in all of the animalderived and human-derived Staphylococcus spp. we tested, including S. aureus, S. epidermidis, S. felis, S. arlettae, S. kloosii, S. pettenkoferi, S. schleiferi, S. sciuri and S. pseudintermedius (Supplementary Table S1 and Supplementary Figure S2).…”

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confidence: 99%

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Intragenus generalized transduction in Staphylococcus spp. by a novel giant phage

et al. 2014

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Bacteriophage (phage)-mediated generalized transduction is expected to contribute to the emergence of drug-resistant staphylococcal clones in various environments. In this study, novel phage S6 was isolated from sewage and used to test generalized transduction in human-and animal-derived staphylococci. Phage S6 was a novel type of giant myophage, which possessed a DNA genome that contained uracil instead of thymine, and it could infect all of the tested staphylococcal species. The phage S6 appeared to be similar to the transducing phage PBS1, which infects Bacillus spp. Moreover, phage S6 facilitated the transduction of a plasmid in Staphylococcus aureus and from S. aureus to non-aureus staphylococcal species, as well as vice versa. Transduction of methicillin resistance also occurred in S. aureus. This is the first report of successful intragenus generalized transduction among staphylococci.

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“…Indeed, human trials with phages against a number of infections have confirmed their safety and shown that phage therapy can provide good results for untreatable chronic infections (12,13). Specifically, recent results showed the efficacy of phages in animal models, such as S. aureus septicemia in mice (14) and in silkworms (15). The safety and efficacy of phage products for removal of this bacterium in a sinusitis sheep model have also been proven (16).…”

mentioning

confidence: 98%

Two Phages, phiIPLA-RODI and phiIPLA-C1C, Lyse Mono- and Dual-Species Staphylococcal Biofilms

Gutiérrez

Vandenheuvel

Martínez

et al. 2015

Appl Environ Microbiol

131

133

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Phage therapy is a promising option for fighting against staphylococcal infections. Two lytic phages, vB_SauM_phiIPLA-RODI (phiIPLA-RODI) and vB_SepM_phiIPLA-C1C (phiIPLA-C1C), belonging to the Myoviridae family and exhibiting wide host ranges, were characterized in this study. The complete genome sequences comprised 142,348 bp and 140,961 bp and contained 213 and 203 open reading frames, respectively. The gene organization was typical of Spounavirinae members, with long direct terminal repeats (LTRs), genes grouped into modules not clearly separated from each other, and several group I introns. In addition, four genes encoding tRNAs were identified in phiIPLA-RODI. Comparative DNA sequence analysis showed high similarities with two phages, GH15 and 676Z, belonging to the Twort-like virus genus (nucleotide identities of >84%); for phiIPLA-C1C, a high similarity with phage phiIBB-SEP1 was observed (identity of 80%). Challenge assays of phages phiIPLA-RODI and phiIPLA-C1C against planktonic staphylococcal cells confirmed their lytic ability, as they were able to remove 5 log units in 8 h. Exposure of biofilms to phages phiIPLA-RODI and phiIPLA-C1C reduced the amount of adhered bacteria to about 2 log units in both monospecies and dual-species biofilms, but phiIPLA-RODI turned out to be as effective as the mixture of both phages. Moreover, the frequencies of bacteriophage-insensitive mutants (BIMs) of Staphylococcus aureus and S. epidermidis with resistance to phiIPLA-RODI and phiIPLA-C1C were low, at 4.05 ؋ 10 ؊7 ؎ 2.34 ؋ 10 ؊9 and 1.1 ؋ 10 ؊7 ؎ 2.08 ؋ 10 ؊9 , respectively. Overall, a generally reduced fitness in the absence of phages was observed for BIMs, which showed a restored phage-sensitive phenotype in a few generations. These results confirm that lytic bacteriophages can be efficient biofilm-disrupting agents, supporting their potential as antimicrobials against staphylococcal infections.T wo staphylococcal species, Staphylococcus aureus and Staphylococcus epidermidis, are the main causes of nosocomial infections due to their ability to adhere to, colonize, and develop biofilms in medical devices and human organs (1). Staphylococcal biofilms are complex structures in which bacterial cells are surrounded by an extracellular material (polysaccharides, teichoic acids, proteins, and extracellular DNA) which confers protection against antibacterial drugs and the host immune system. In addition, growth of bacteria in a biofilm facilitates the development of antibiotic-resistant organisms (2). S. epidermidis is one of the most abundant species in the human skin microbiota, from which it easily reaches catheters, heart valves, and contact lenses. Despite being regarded as an innocuous bacterium, it is now accepted as an opportunistic pathogen and one of the most common causes of bacteremia in immunocompromised patients (3), preterm infants (4), and biofilm-related infections (5). In addition, resistance to methicillin due to the presence of the mecA gene is widely spread in hospital isolates (6). Similarly, virule...

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Evaluating efficacy of bacteriophage therapy againstStaphylococcus aureusinfections using a silkworm larval infection model

Cited by 42 publications

References 23 publications

Perspective: The age of the phage

Perspective: The age of the phage

Intragenus generalized transduction in Staphylococcus spp. by a novel giant phage

Two Phages, phiIPLA-RODI and phiIPLA-C1C, Lyse Mono- and Dual-Species Staphylococcal Biofilms

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