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Background: Salmonella enterica serotype Typhi is one of the major pathogens causing typhoid fever and a public health burden worldwide. Recently, the increasing number of multidrug-resistant strains of Salmonella spp. has made this utmost necessary to consider bacteriophages as a potential alternative to antibiotics for S. Typhi infection treatment. Salmonella phage STWB21, isolated from environmental water, has earlier been reported to be effective as a safe biocontrol agent by our group. In this study, we evaluated the efficacy of phage STWB21 in reducing the burden of salmonellosis in a mammalian host by inhibiting Salmonella Typhi invasion into the liver and spleen tissue., Results: Phage treatment significantly improved the survival percentage of infected mice. This study also demonstrated that oral administration of phage treatment could be beneficial in both preventive and therapeutic treatment of salmonellosis caused by S. Typhi. Altogether the result showed that the phage treatment could control tissue inflammation in mice before and after Salmonella infection., Conclusions: To the best of our knowledge, this is the first report of phage therapy in a mouse model against a clinically isolated Salmonella Typhi strain that includes direct visualization of histopathology and ultrathin section microscopy images from the liver and spleen sections., (© 2023. The Author(s).)

Antimicrobial resistance (AMR) is a major problem and an immediate alternative to antibiotics is the need of the hour. Research on the possible alternative products to tackle bacterial infections is ongoing worldwide. One of the most promising alternatives to antibiotics is the use of bacteriophages (phage) or phage-driven antibacterial drugs to cure bacterial infections caused by AMR bacteria. Phage-driven proteins, including holins, endolysins, and exopolysaccharides, have shown great potential in the development of antibacterial drugs. Likewise, phage virion proteins (PVPs) might also play an important role in the development of antibacterial drugs. Here, we have developed a machine learning-based prediction method to predict PVPs using phage protein sequences. We have employed well-known basic and ensemble machine learning methods with protein sequence composition features for the prediction of PVPs. We found that the gradient boosting classifier (GBC) method achieved the best accuracy of 80% on the training dataset and an accuracy of 83% on the independent dataset. The performance on the independent dataset is better than other existing methods. A user-friendly web server developed by us is freely available to all users for the prediction of PVPs from phage protein sequences. The web server might facilitate the large-scale prediction of PVPs and hypothesis-driven experimental study design.

Bacterial infections continue to jeopardize human and animal health, impacting millions of lives by causing significant deaths every year. The use of antibiotics remains the primary choice of therapy and has only been partly successful in reducing the disease burden due to the evolving nature of resistant microbes. Widespread and inappropriate use of antibiotics resulted in the development of antibiotic-resistant microbial species provoking substantial economic burdens. The most promising way to resolve the issue of antibiotic resistance is the use of bacterial viruses called bacteriophages to treat microbial infections. Earlier reports on experimental bacteriophage therapy showed successful patient outcomes, and many clinical trials of such clinical bacteriophages have already been investigated in many western countries. In this review, we are focusing on the advantages as well as drawbacks of bacteriophage therapy to use it as an alternative to antibiotics for microbial infections, together with its current success status. There is also a need to extensively study the past, present, and future outlook of phage therapy in comparison to presently available antimicrobial agents and especially immunological response by the host after phage administration. Our aim is to highlight the fast-promoting field of bacteriophage therapy and provocations that lie ahead as the world is gradually moving aside from complete dependence on antimicrobial agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Antimicrobial resistance (AMR) in bacteria is an important global health problem affecting humans, animals, and the environment. AMR is considered as one of the major components in the "global one health". Misuse/overuse of antibiotics in any one of the segments can impact the integrity of the others. In the presence of antibiotic selective pressure, bacteria tend to develop several defense mechanisms, which include structural changes of the bacterial outer membrane, enzymatic processes, gene upregulation, mutations, adaptive resistance, and biofilm formation. Several components of mobile genetic elements (MGEs) play an important role in the dissemination of AMR. Each one of these components has a specific function that lasts long, irrespective of any antibiotic pressure. Integrative and conjugative elements (ICEs), insertion sequence elements (ISs), and transposons carry the antimicrobial resistance genes (ARGs) on different genetic backbones. Successful transfer of ARGs depends on the class of plasmids, regulons, ISs proximity, and type of recombination systems. Additionally, phage-bacterial networks play a major role in the transmission of ARGs, especially in bacteria from the environment and foods of animal origin. Several other functional attributes of bacteria also get successfully modified to acquire ARGs. These include efflux pumps, toxinantitoxin systems, regulatory small RNAs, guanosine pentaphosphate signaling, quorum sensing, two-component system, and clustered regularly interspaced short palindromic repeats (CRISPR) systems. The metabolic and virulence state of bacteria is also associated with a range of genetic and phenotypic resistance mechanisms. In spite of the availability of a considerable information on AMR, the network associations between selection pressures and several of the components mentioned above are poorly understood. Understanding how a pathogen resists and regulates the ARGs in response to antimicrobials can help in controlling the development of resistance. Here, we provide an overview of the importance of genetic network and regulation of AMR in bacterial pathogens. [ABSTRACT FROM AUTHOR]

Salmonella is one of the common causal agents of bacterial gastroenteritisrelated morbidity and mortality among children below 5 years and the elderly populations. Salmonellosis in humans is caused mainly by consuming contaminated food originating from animals. The genus Salmonella has several serovars, and many of them are recently reported to be resistant to multiple drugs. Therefore, isolation of lytic Salmonella bacteriophages in search of bactericidal activity has received importance. In this study, a Salmonella phage STWB21 was isolated from a lake water sample and found to be a novel lytic phage with promising potential against the host bacteria Salmonella typhi. However, some polyvalence was observed in their broad host range. In addition to S. typhi, the phage STWB21 was able to infect S. paratyphi, S. typhimurium, S. enteritidis, and a few other bacterial species such as Sh. flexneri 2a, Sh. flexneri 3a, and ETEC. The newly isolated phage STWB21 belongs to the Siphoviridae family with an icosahedral head and a long flexible non-contractile tail. Phage STWB21 is relatively stable under a wide range of pH (4–11) and temperatures (4°C–50°C) for different Salmonella serovars. The latent period and burst size of phage STWB21 against S. typhi were 25 min and 161 plaque-forming units per cell. Since Salmonella is a foodborne pathogen, the phage STWB21 was applied to treat a 24 h biofilm formed in onion and milk under laboratory conditions. A significant reduction was observed in the bacterial population of S. typhi biofilm in both cases. Phage STWB21 contained a dsDNA of 112,834 bp in length, and the GC content was 40.37%. Also, genomic analysis confirmed the presence of lytic genes and the absence of any lysogeny or toxin genes. Overall, the present study reveals phage STWB21 has a promising ability to be used as a biocontrol agent of Salmonella spp. and proposes its application in food industries. [ABSTRACT FROM AUTHOR]

Cholera continues to be a major burden for developing nations, especially where sanitation, quality of water supply, and hospitalization have remained an issue. Recently, growing antimicrobial-resistant strains of Vibrio cholerae underscores alternative therapeutic strategies for cholera. Bacteriophage therapy is considered one of the best alternatives for antibiotic treatment. For the identification of potential therapeutic phages for cholera, we have introduced a comprehensive comparative analysis of whole-genome sequences of 86 Vibrio cholerae phages. We have witnessed extensive variation in genome size (ranging from 33 to 148 kbp), GC (G + C) content (varies from 34.5 to 50.8%), and the number of proteins (ranging from 15 to 232). We have identified nine clusters and three singletons using BLASTn, confirmed by nucleotide dot plot and sequence identity. A high degree of sequence and functional similarities in both the genomic and proteomic levels have been observed within the clusters. Evolutionary analysis confirms that phages are conserved within the clusters but diverse between the clusters. For each therapeutic phage, the top 2 closest phages have been identified using a system biology approach and proposed as potential therapeutic phages for cholera. This method can be applied for the classification of the newly isolated Vibrio cholerae phage. Furthermore, this systematic approach might be useful as a model for screening potential therapeutic phages for other bacterial diseases. [ABSTRACT FROM AUTHOR]

Phages, such as those infecting Bacteroides spp., have been proven to be reliable indicators of human fecal contamination in microbial source tracking (MST) studies, and the efficacy of these MST markers found to vary geographically. This study reports the application and evaluation of candidate MST methods (phages infecting previously isolated B. fragilis strain GB-124, newly isolated Bacteroides strains (K10, K29, and K33) and recently isolated Kluyvera intermedia strain ASH-08), along with non-source specific somatic coliphages (SOMCPH infecting strain WG-5) and indicator bacteria (Escherichia coli) for identifying fecal contamination pathways in Kolkata, India. Source specificity of the phage-based methods was first tested using 60 known non-human fecal samples from common animals, before being evaluated with 56 known human samples (municipal sewage) collected during both the rainy and dry season. SOMCPH were present in 40-90% of samples from different animal species and in 100% of sewage samples. Phages infecting Bacteroides strain GB-124 were not detected from the majority (95%) of animal samples (except in three porcine samples) and were present in 93 and 71% of the sewage samples in the rainy and dry season (Mean = 1.42 and 1.83 log10PFU/100mL, respectively), though at lower levels than SOMCPH (Mean = 3.27 and 3.02 log10PFU/100mL, respectively). Phages infecting strain ASH-08 were detected in 89 and 96% of the sewage samples in the rainy and dry season, respectively, but were also present in all animal samples tested (except goats). Strains K10, K29, and K30 were not found to be useful MST markers due to low levels of phages and/or co-presence in non-human sources. GB-124 and SOMCPH were subsequently deployed within two low-income neighborhoods to determine the levels and origin of fecal contamination in 110 environmental samples. E. coli , SOMCPH, and phages of GB-124 were detected in 68, 42, and 28% of the samples, respectively. Analyses of 166 wastewater samples from shared community toilets and 21 samples from sewage pumping stations from the same districts showed that SOMCPH were present in 100% and GB-124 phages in 31% of shared toilet samples (Median = 5.59 and <1 log10 PFU/100 mL, respectively), and both SOMCPH and GB-124 phages were detected in 95% of pumping station samples (Median = 5.82 and 4.04 log10 PFU/100 mL, respectively). Our findings suggest that GB-124 and SOMCPH have utility as low-cost fecal indicator tools which can facilitate environmental surveillance of enteric organisms, elucidate human and non-human fecal exposure pathways, and inform interventions to mitigate exposure to fecal contamination in the residential environment of Kolkata, India. Phages infecting Bacteroides fragilis strain GB-124 and non-source specific somatic coliphages (SOMCPH) were deployed for identification of fecal contamination pathways in Kolkata, India. Analyses of environmental samples representative of nine different exposure pathways, pooled sewage from shared community toilets and sewage from pumping stations showed the presence of both SOMCPH and GB-124 phages in all the sample types. [ABSTRACT FROM AUTHOR]

Background: Cholera is a primordial disease caused by Vibrio cholerae which existed from centuries in different parts of the world and still shows its periodic, endemic and epidemic presence. Thousands of cholera cases are reported from different parts of India and the disease remains endemic throughout the year. At present, we do not have enough knowledge about the phenotypic nature of the circulating V. cholerae strains in this part of the world. Objectives: This study was carried out over a period of 6 years with the aim defer with the changes in the prevalence and distribution of biotypes, serotypes and phage types of V. cholerae clinical isolates from various endemic regions of the country to determine phenotypic characteristics of the circulating strains and also to predict the attributes of cholera strains responsible for causing significant outbreaks in future. Materials and Methods: A total of 1882 V.cholerae O1 isolates from different cholera endemic areas of India were included in this study. V.cholerae strains which were identified as O1 biotype ElTor further analyzed for serotype and phage types using the standard methodologies. Polyvalent O1 and monospecific Inaba and Ogawa antisera were used for serotyping. A panel of five phages of Basu and Mukherjee phage typing scheme and five phages from the new phage typing scheme were used for phage typing analysis following standard methodology. Results: Maximum numbers of strains were isolated from cholera-endemic states like Gujarat and Maharashtra. All the isolates were confirmed as V. cholerae O1 biotype ElTor and majority of them were serotype Ogawa (93.2%). New phage typing scheme resulted in almost 100% typeable V. cholerae O1 strains included in this study and phage type 27 was the predominant type. Although 80% of the strains used in this study were sensitive to all the vibrio phages, S5 phage was found most efficient in lysing cholera strains indicating its broader host range. Conclusion: The current study identified phage type 27 as the most dominant type and serotype Ogawa was found continuous in circulation throughout the year which has caused recent cholera outbreaks in India during the past years. Phage sensitivity data propose an alternative cost-effective approach to prevent cholera outbreak by therapeutic uses of typing phages irrespective of origin or clonality of the strains. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]