Genomic and Proteomic Characterizations of Sfin-1, a Novel Lytic Phage Infecting Multidrug-Resistant Shigella spp. and Escherichia coli C

Abstract

Shigellosis is a public health threat in developed as well as developing countries like “India.” While antibiotic therapy is the mainstay of treatment for shigellosis, current emergence of multidrug-resistant strains of Shigella spp. has posed the problem more challenging. Lytic bacteriophages which destroy antibiotic resistant Shigella spp. have great potential in this context and hence their identification and detailed characterization is necessary. In this study we presented the isolation and a detailed characterization of a novel bacteriophage Sfin-1 , which shows potent lytic activity against multidrug-resistant isolates of Shigella flexneri , Shigella dysenteriae , Shigella sonnei obtained from clinical specimens from shigellosis patients. It is also active against Escherichia coli C. The purified phage is lytic in nature, exhibited absorption within 5–10 min, a latent period of 5–20 min and burst size of ∼28 to ∼146 PFU/cell. The isolated phage shows stability in a broad pH range and survives an hour at 50°C. Genome sequencing and phylogenetic analyses showed that Sfin-1 is a novel bacteriophage, which is very closely related to T1-like phages (89.59% identity with Escherichia virus T1). In silico analysis indicates that Sfin-1 genome consists of double stranded linear DNA of 50,403 bp (GC content of 45.2%) encoding 82 potential coding sequences, several potential promoters and transcriptional terminators. Under electron microscopy, Sfin-1 shows morphology characteristics of the family Siphoviridae with an isometric head (61 nm) and a non-contractile tail (155 nm). This is most likely the first report of a lytic bacteriophage that is active against three of the most virulent multidrug-resistant Shigella species and therefore might have a potential role in phage therapy of patients infected with these organisms.

Isolation, phenotypic characterization and comparative genomic analysis of 2019SD1, a polyvalent enterobacteria phage

“…Accordingly, the maximum number of progenies released from one host bacterium was recorded as 151 PFU bacterial cell −1 . Although the latent period was fairly similar to the one observed for vB_SflS-ISF001 (20 min) 30 , but was markedly higher or lower than that recorded for pSf-2 (30 min) 56 , SH6 phage (16 min) 55 and Sfin-1 (15 min for S. dysenteriae and 10 min for S. sonnei ) 29 . Interestingly, the burst size of 2019SD1 was greater than that of other reported Shigella phages of Drexlerviridae family like pSf-2 (16 PFU infected cell −1 ) 56 , SH6 phage (103 ± 16 PFU infected cell −1 ) 55 and SsoS-ISF002 (76 ± 9 PFU infected cell −1 ) 27 .…”

“…1 A). The plaque size was nearly similar to that observed for other Shigella phages namely vB_SsoS_008 (2.5–2.7 mm) 52 , but markedly higher or lower than that recorded for pSf-1 (4.5 mm) 53 , JK16 (4 mm) 28 , vB-SdyS-ISF003 (3 mm) 50 SsoS-ISF002 (0.5 to 3.0 mm) 27 , SH6 (2 mm) 54 , Sfin-1(1.5–2.0 mm) 29 , vB_SflS-ISF001 (0.5–2.0 mm) 30 . Analysis of TEM images of phage particles suggested that the 2019SD1 had an icosahedral capsid (60 ± 5 nm dia) and a 140 ± 6 nm long tail (Fig.…”

“…Some of the phages reported against Shigella species include sf6 24 , SfIV 25 , SfI 26 , vB_SsoS-ISF002 27 and vB_SsoS-ISF003 28 . More recently, a new phage, Sfin-1, showing potent lytic activity against multidrug-resistant isolates of S. flexneri , S. dysenteriae and S. sonnei has been described from India 29 . However, limited studies are available on detailed biological properties and whole genome analysis of lytic phages infecting S. dysenteriae 30 and other bacteria from Enterobacteriaceae family.…”

Potential for Phages in the Treatment of Bacterial Sexually Transmitted Infections

“…The isolated N. gonorrhoeae [ 36 ] lysogenic phage is from an activated prophage within its genome, while S. agalactiae [ 59 , 61 , 62 , 113 ] phages have been isolated environmentally. Shigella flexneri and S. sonnei have virulent phages [ 102 , 103 , 104 , 105 , 106 ], some of which are being used clinically to treat shigellosis [ 25 , 98 ]. However, these treatments have not been considered for use in the treatment of STIs, as historically, shigellosis is obtained through the traditional fecal–oral route.…”

Isolation and Characterization of Bacillus cereus Phage vB_BceP-DLc1 Reveals the Largest Member of the Φ29-Like Phages

“…When compared with some other B. cereus phages [66][67][68], the burst size of DLc1 is relatively low and the latent period is shorter (Figure 8B). Although it has been shown that a large burst size is preferred in phage therapy [69], DLc1 with a short latent period and high adsorption efficacy also displayed its advantages.…”