Role Of Phages Research Articles

β-lactam resistance genes in bacteriophage and bacterial DNA from wastewater, river water, and irrigation water in Washington State

Our objective was to determine whether β-lactamase genes are carried within bacteriophage capsids, as a first step towards exploring the possible role of bacteriophages as vehicles for dispersal of antimicrobial resistance genes through an agricultural region of Washington State. Water samples (n = 178) from municipal wastewater treatment plants, river and irrigation canals were collected over a period of eight months. The occurrence of four β-lactam resistance gene groups (blaTEM, blaCTX-M, blaPSE and blaCMY-2) and three carbapenem resistance genes (blaKPC, blaOXA-48-like, and blaNDM) in bacterial and phage fractions of water samples was evaluated by PCR. All of the seven targeted resistance genes were detected both in wastewater and river water samples. Relatively high proportions of samples (7.3%–64.9%) positive for resistance genes were found in bacteriophage fractions of water samples compared to the bacterial fractions (5.4%–36.8%). blaOXA-48-like (57.3%) and blaTEM (64.0%) were the most prevalent antimicrobial resistance genes detected at all the sampling points. Resistance genes are commonly present in treated wastewater flowing through municipal and agricultural environments, indicating a plausible role for this water in the dissemination of antimicrobial resistance traits, including blaCTX-M.

Phages Mediate Bacterial Self-Recognition

Cells are social, and self-recognition is a conserved aspect of group behavior where cells assist kin and antagonize non-kin. However, the role of phage in self-recognition is unexplored. Here we find that ademarcation line is formed between different swimming Escherichia coli strains but not between identical clones; hence, motile cells discriminate between self and non-self. The basis for this self-recognition is a 49 kb, T1-type, lytic phage of the family Siphoviridae (named here SW1) that controls formation of the demarcation line by utilizing one of the host's cryptic prophage proteins, YfdM of CPS-53, to propagate. Critically, SW1 provides a conditional benefit to E.coli K-12 compared with the identical strain that lacks the phage. A demarcation line is also formed when strains harbor either the lysogenic phage ϕ80 or lambda and encounter siblings that lack the lysogen. In summary, bacteria can use phage to distinguish siblings that lack phage.

Application of filamentous phages in environment: A tectonic shift in the science and practice of ecorestoration.

Theories in soil biology, such as plant–microbe interactions and microbial cooperation and antagonism, have guided the practice of ecological restoration (ecorestoration). Below‐ground biodiversity (bacteria, fungi, invertebrates, etc.) influences the development of above‐ground biodiversity (vegetation structure). The role of rhizosphere bacteria in plant growth has been largely investigated but the role of phages (bacterial viruses) has received a little attention. Below the ground, phages govern the ecology and evolution of microbial communities by affecting genetic diversity, host fitness, population dynamics, community composition, and nutrient cycling. However, few restoration efforts take into account the interactions between bacteria and phages. Unlike other phages, filamentous phages are highly specific, nonlethal, and influence host fitness in several ways, which make them useful as target bacterial inocula. Also, the ease with which filamentous phages can be genetically manipulated to express a desired peptide to track and control pathogens and contaminants makes them useful in biosensing. Based on ecology and biology of filamentous phages, we developed a hypothesis on the application of phages in environment to derive benefits at different levels of biological organization ranging from individual bacteria to ecosystem for ecorestoration. We examined the potential applications of filamentous phages in improving bacterial inocula to restore vegetation and to monitor changes in habitat during ecorestoration and, based on our results, recommend a reorientation of the existing framework of using microbial inocula for such restoration and monitoring. Because bacterial inocula and biomonitoring tools based on filamentous phages are likely to prove useful in developing cost‐effective methods of restoring vegetation, we propose that filamentous phages be incorporated into nature‐based restoration efforts and that the tripartite relationship between phages, bacteria, and plants be explored further. Possible impacts of filamentous phages on native microflora are discussed and future areas of research are suggested to preclude any potential risks associated with such an approach.

Going Viral: a Novel Role for Bacteriophage in Colorectal Cancer.

Microbiome-based signatures of disease have focused primarily on the bacterial component of the microbiome for numerous reasons, including ease of sample preparation and depth of the curated bacterial database. However, even more numerous than bacteria are the bacteriophages of the viral portion of the microbiome, which have emerged with identifiable disease signatures in other diseases, such as inflammatory bowel diseases. Here, G. D. Hannigan, M. B. Duhaime, M. T. Ruffin, IV, C. C. Koumpouras, and P. D. Schloss (mBio 9:e02248-18, https://doi.org/10.1128/mBio.02248-18) present a study that explores the potential bacteriophage signatures in patients with colorectal cancer (CRC) and the associated changes in bacterial signatures. Sampling from a cross section of 60 patients at different stages of CRC in addition to 30 healthy controls, this study highlights the need for greater exploration into the virome, including the "dark matter" of diverse forms that viruses assume in the gastrointestinal tract.

Role of Bacteriophages in the Implementation of a Sustainable Dairy Chain.

The growing human population is currently facing an unprecedented challenge regarding global food sustainability. Thus, it is of paramount to maintain food production and quality while avoiding a negative impact on climate change and the environment at large. Along the food chain, several practices could compromise future food safety and human health. One example is the widespread use of antibiotics and disinfectants in dairy production, which has contributed to the current antibiotic resistance crisis. Moreover, the uncontrolled release of antimicrobials to the environment poses a significant threat to natural ecosystems. For these reasons, research has recently focused on exploiting natural antimicrobials with the goal of achieving a safer and more sustainable dairy production chain. In this context, bacteriophages, viruses that infect bacteria, may become good allies to prevent and treat diseases in cattle, or be used as disinfectants in dairy facilities and as preservatives in dairy products. This review provides an overview of the current research regarding the use of phages as a global approach to reduce economic losses and food waste, while increasing food safety and reducing the environmental impact of food production. Our current understanding of progress, solutions, and future challenges in dairy production, processing, safety, waste processing, and quality assurance is also discussed.

Role of phage \u03d51 in two strains of Salmonella Rissen, sensitive and resistant to phage \u03d51

BackgroundThe study describes the Salmonella Rissen phage ϕ1 isolated from the ϕ1-sensitive Salmonella Rissen strain RW. The same phage was then used to select the resistant strain RRϕ1+, which can harbour or not ϕ1.ResultsFollowing this approach, we found that ϕ1, upon excision from RW cells with mitomycin, behaves as a temperate phage: lyses host cells and generates phage particles; instead, upon spontaneous excision from RRϕ1+ cells, it does not generate phage particles; causes loss of phage resistance; switches the O-antigen from the smooth to the rough phenotype, and favors the transition of Salmonella Rissen from the planktonic to the biofilm growth.The RW and RRϕ1+ strains differ by 10 genes; of these, only two (phosphomannomutase_1 and phosphomannomutase_2; both involved in the mannose synthesis pathway) display significant differences at the expression levels. This result suggests that phage resistance is associated with these two genes.ConclusionsPhage ϕ1 displays the unusual property of behaving as template as well as lytic phage. This feature was used by the phage to modulate several phases of Salmonella Rissen lifestyle.

Antibiotic resistance genes in bacteriophages from diverse marine habitats

Although antibiotic resistance represents a significant and growing threat to human and environmental health worldwide, the contribution of bacteriophages (phages) to the acquisition and spread of antibiotic resistance genes (ARGs) in the environment has not been extensively explored. In this study, a comprehensive analysis of several viromes from diverse marine habitats was performed to investigate whether or not phages carry ARGs. The analysis provides strong evidence that phages from marine habitats are potential reservoirs of ARGs. In fact, genes conferring resistance to aminocoumarin, bacitracin and multidrug resistance (particularly the mexB gene) were found in all analyzed marine viromes. Given this, the role of phages as reservoirs of ARGs should not be underestimated considering their global distribution.

A century of bacteriophage research and applications: impacts on biotechnology, health, ecology and the economy!

AbstractAbout a century ago, bacteriophages or phages – viruses that infect bacteria – were discovered and reported in the scientific literature. This review aims at a comprehensive survey of bacteriophage discovery, research and applications since the 1920s, and its impact on molecular biology, biotechnology, health, ecology and the economy. Phage therapy has been proven a valuable asset to deal with pathogenic bacterial infections since the early 1920s, and has been practiced ever since, especially in the former Soviet Union and in Eastern Europe. The Western world remained sceptical and resorted to the widespread use of antibiotics since the 1940s. Now that antibiotic resistance among pathogenic bacteria has spread alarmingly and few really novel antibiotic compounds are in the pipeline, renewed attention is being directed to the use of phages as antibacterial agents in medicine. Because of this renewed interest in phage therapy in the Western world, novel applications with phages are being pursued in the human health, environmental and the agri‐food sectors. This review will focus on (1) the history of early phage use and its successes and problems, (2) the study of phages as important tools in the development of molecular biology and biotechnology, (3) current developments in phage research including the use of phage endolysins for use in antibacterial treatment, (4) phage production systems including undesirable phage contamination of industrial fermentation processes based on bacteria, (5) recent applications in phage therapy and in phage‐based control, and (6) the roles of phages in nature and in the human gut. © 2018 Society of Chemical Industry

The Russian Italian Round Table in the N. A. Semashko National Research Institute of Public Health about the Problem of In-Hospital Infectious Diseases and Antibiotic Resistance

The article presents the results of information exchange within the framework of the Russian Italian round about the problem of in-hospital infectious diseases and antibiotic resistance and the role of bacteriophages in inhibition and prevalence of antimicrobial resistance organized and carried out in The Federal State Budget Scientific Institution «N. A. Semashko National Research Institute of Public Health» (Moscow, Russia).

Staphylococcus aureus biofilm and the role of bacteriophages in its eradication

The ability to form biofilm is an important virulence factor of many microorganisms. Infections involving biofilms account for approx. 65% of all human infections. Biofilms may develop on intravascular catheters or implanted devices such as prosthetic heart valves. Implanted devices are covered by biofilm and become reservoirs of microorganisms which can be a cause of persistent infections (endocarditis, deep tissue abscesses, septic arthritis, and osteomyelitis). Treatment of infections caused by biofilm-growing cells is linked to a high risk of failure due to an extreme resistance to antimicrobial agents and increased capacity to evade the immune responses. A large number of biofilm-associated infections involve Staphylococcus aureus. Treatment of staphylococcal infections is a great challenge for clinicians because of the presence of various mechanisms of resistance to antibiotics in S. aureus, for example methicillin resistance and biofilm production. Therapeutic difficulties related with antibiotic-resistant bacteria and limitations in research on new antimicrobials were the reasons that nearly 100 years after discovery, bacteriophages caught the attention of scientists around the world as a new therapeutic option for bacterial infections. Numerous in vitro studies on S. aureus strains showed that phages can both prevent biofilm formation and contribute to the elimination of bacteria from the mature biofilm structure. The major role in biofilm eradication play depolymerases produced by some phages which facilitate their penetration into the inner layers of biofilm by disturbing the biofilm structure. This leads to the conclusion that bacteriophages treatment might become a new strategy in the prevention and eradication of infectious bacterial biofilms, including these formed by S. aureus.

Biology of Vibrio cholera. Editorial overview.

In this monographic issue, we have the pleasure to present contributions from six of the leading laboratories at the forefront of Vibrio cholerae genetics, ecology and evolution, together with a brief tribute by Diego Romero to Doctor Jaime Ferrán y Clua, a pioneering Spanish bacteriologist who developed the first vaccine against this pathogen. V. cholerae is a free-living aquatic bacterium that interacts with and infects a variety of organisms. In humans it causes cholera, the deadly diarrhoea that was responsible for millions of deaths during seven pandemics since 1817, and still thousands every year. The Boucher lab presents a study of the ecology, evolution and dispersal of pandemic V. cholerae biotypes in relation to environmental reservoirs. They show how both species-specific and lineage-specific genetic determinants play a role in the ability of V. cholerae strains to cause pandemics, having evolved gradually over centuries. One of the key aspects that makes a particularly successful pathogen is its genomic plasticity. The V. cholerae genome contains a superintegron (SI) that is involved in development and dissemination of antibiotic resistance genes among diverse bacterial species, permitting population expansion in challenging conditions. Escudero and Mazel review the SI as a true hotspot of V. cholerae's genomic diversity and low-cost memory of adaptive functions in its complex lifestyle and ecology. Another remarkable aspect of V. cholerae 's genetics is the presence of two chromosomes. Segregation and division in multi-chromosomal becteria is relatively complex, and V. cholerae remains the paradigm. Espinosa and colleagues review the cell cycle of V. cholerae , comparing and contrasting with that of E. coli . In addition to genome plasticity, V. cholerae uses a variety of attack/defence strategies to compete and thrive in different niches, through interaction with bacteriophages, bacteria and eukaryotes. The role of phages in the life cycle of V. cholerae has been increasingly recognized and investigated over the past decade. Andrew Camilli and colleagues take us through the exciting evolutionary arms race between V. cholerae and virulent bacteriophages, based both on mechanisms of phage resistance in the bacterium and a unique phage-encoded CRISPR-Cas system used to counteract this resistance. Finally, the authors discuss the impact of these predator-prey dynamics in the context of infection, and their use as a strategy to limit cholera transmission within a community. In regards to its ability to coexist with other microbes, V. cholerae can produce effectors that are either released to the extracellular media, or delivered via intimate cell-to-cell contact such as those injected via the type VI secretion system (T6SS). The Pukatzki lab reviews the versatility of the T6SS to produce different combinations of such effectors, which establishes the strains of V. cholerae that can co-exist in the environment. After killing a cell, its DNA is released and incorporated by natural competence into other living cells, thereby being a potential source of diversification for V. cholerae's T6SS effectors. Finally, I revisisit the discovery of non-canonical D-amino acids, recently identified effectors secreted by V. cholerae which have increasingly been shown to be important in enhancing the ability of the bacterium to colonize and persist in a particular niche. I focus on recent observations that suggest different D-amino acids influence distinct cellular processes in bacteria, and dis cuss their role in modulating environmental bacterial biodiversity.

The role of bacteriophages in the complex treatment of peritonitis of appendicular origin (experimental study)

Relevance: with the management of laparoscopic methods of surgical treatment of acute appendicitis, the problem of the occurrence of early postoperative complications has not changed at present, which makes it necessary to carry out preventive measures.
 Objective: to study the possibility of improving the results of surgical treatment of peritonitis, the most frequent complication of acute appendicitis, by reducing the number of postoperative complications of infectious genesis.
 Methods: Studies were performed on 47 non-linear white rats weighing 200-250 grams by modelling peritonitis using the biological model as an example, followed by antibiotic therapy and combination therapy using bacteriophages. To model peritonitis, the infection of the abdominal cavity with the E. coli strain 25922 was used. The laboratory animals were divided into 3 groups: the first group was control group, the second group received treatment in the form of a single intraperitoneal injection of Cefipime, the third group received treatment as a single intraperitoneal injection of the Sextapage.
 Results: the evaluation of the methods was carried out on the basis of the study of the clinical picture of the course of peritonitis in experimental animals, the data of pathomorphological and histological examination of the sectional peritoneum. As a result of experimental studies, there was no significant difference in the methods of perioperative prevention of complications of acute appendicitis, which makes it possible to perform monotherapy with bacteriophages. Phages in comparison with antibiotics have no less therapeutic efficacy.
 Conclusions: Thus, our experimental studies revealed completely satisfactory results of monotherapy of experimental peritonitis with a bacteriophage. According to the morphological data, the inflammatory process in the abdominal cavity is stopped by the phage fast enough and there is a tendency for a faster fading of the inflammation than in the treatment with antibiotics.

Mechanisms of the evolutionary arms race between Vibrio cholerae and Vibriophage clinical isolates.

This review highlights recent findings on the evolutionary arms race between the causative agent of cholera Vibrio cholerae and virulent bacteriophages (phages) ICP1, ICP2, and ICP3 isolated from cholera patient stool samples. We discuss mechanisms of phage resistance such as a unique phage-inhibitory chromosomal island and mutations that affect phage receptor expression. We also discuss the molecular characterization of ICP1 and its unique CRISPR-Cas system, which it uses to combat the phage-inhibitory chromosomal island. The role of phages in the life cycle of V. cholerae has been increasingly recognized and investigated in the past decade. This article will review hypotheses as to how the predator-prey relationship may have an impact on infections within individuals and on the self-limiting nature of cholera epidemics. In addition, we put forth a strategy of using phages as an intervention to reduce household transmission of cholera within a community.

Bacteriophages as potential new mammalian pathogens

Increased intestinal permeability and translocation of gut bacteria trigger various polyaetiological diseases associated with chronic inflammation and underlie a variety of poorly treatable pathologies. Previous studies have established a primary role of the microbiota composition and intestinal permeability in such pathologies. Using a rat model, we examined the effects of exposure to a bacteriophage cocktail on intestinal permeability and relative abundance of taxonomic units in the gut bacterial community. There was an increase in markers of impaired gut permeability, such as the lactulose/mannitol ratio, plasma endotoxin concentrations, and serum levels of inflammation-related cytokines, following the bacteriophage challenge. We observed significant differences in the alpha diversity of faecal bacterial species and found that richness and diversity index values increased following the bacteriophage challenge. There was a reduction in the abundance of Blautia, Catenibacterium, Lactobacillus, and Faecalibacterium species and an increase in Butyrivibrio, Oscillospira and Ruminococcus after bacteriophage administration. These findings provide novel insights into the role of bacteriophages as potentially pathogenic for mammals and their possible implication in the development of diseases associated with increased intestinal permeability.

Three novel Pseudomonas phages isolated from composting provide insights into the evolution and diversity of tailed phages

BackgroundAmong viruses, bacteriophages are a group of special interest due to their capacity of infecting bacteria that are important for biotechnology and human health. Composting is a microbial-driven process in which complex organic matter is converted into humus-like substances. In thermophilic composting, the degradation activity is carried out primarily by bacteria and little is known about the presence and role of bacteriophages in this process.ResultsUsing Pseudomonas aeruginosa as host, we isolated three new phages from a composting operation at the Sao Paulo Zoo Park (Brazil). One of the isolated phages is similar to Pseudomonas phage Ab18 and belongs to the Siphoviridae YuA-like viral genus. The other two isolated phages are similar to each other and present genomes sharing low similarity with phage genomes in public databases; we therefore hypothesize that they belong to a new genus in the Podoviridae family. Detailed genomic descriptions and comparisons of the three phages are presented, as well as two new clusters of phage genomes in the Viral Orthologous Clusters database of large DNA viruses. We found sequences encoding homing endonucleases that disrupt a putative ribonucleotide reductase gene and an RNA polymerase subunit 2 gene in two of the phages. These findings provide insights about the evolution of two-subunits RNA polymerases and the possible role of homing endonucleases in this process. Infection tests on 30 different strains of bacteria reveal a narrow host range for the three phages, restricted to P. aeruginosa PA14 and three other P. aeruginosa clinical isolates. Biofilm dissolution assays suggest that these phages could be promising antimicrobial agents against P. aeruginosa PA14 infections. Analyses on composting metagenomic and metatranscriptomic data indicate association between abundance variations in both phage and host populations in the environment.ConclusionThe results about the newly discovered and described phages contribute to the understanding of tailed bacteriophage diversity, evolution, and role in the complex composting environment.

The Efficacy of Isolated Bacteriophages from Pig Farms against ESBL/AmpC-Producing Escherichia coli from Pig and Turkey Farms.

Extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases are plasmid (but also chromosomally) encoded enzymes found in Enterobacteriaceae, determining resistance to a variety of important antibiotics including penicillins, cephalosporins, and monobactams. In recent decades, the prevalence of ESBL/AmpC-producing bacteria has increased rapidly across the world. Here, we evaluate the potential use of bacteriophages in terms of a reduction of antibiotic-resistant bacteria in healthy animals. The aim of our studies was to isolate bacteriophages capable of destroying ESBL/AmpC-producing Escherichia coli isolated from livestock habitats. The efficacy of isolated phages against ESBL/AmpC E. coli strains varies, but creation of a phage cocktail with broad activity spectrum is possible. This may indicate that the role of phages may not be limited to phage therapy, but bacterial viruses may also be applied against spread of bacteria with antibiotic resistance genes in the environment. We also addressed the hypothesis, that phages, effective for therapeutic purposes may be isolated from distant places and even from different environments other than the actual location of the targeted bacteria. This may be beneficial for practical purposes, as the construction of effective phage preparations does not require access to disease outbreaks.

Exploring the contribution of bacteriophages to antibiotic resistance

Bacteriophages (phages) are the most abundant and diverse biological entities in our planet. They infect susceptible bacterial hosts into which they either multiply or persist. In the latter case, phages can confer new functions to their hosts as a result of gene transfer, thus contributing to their adaptation (short-term) and evolution (long-term). In this regard, the role of phages on the dissemination of antibiotic resistance genes (ARGs) among bacterial hosts in natural environments has not yet been clearly resolved. Here, we carry out a comprehensive analysis of thirty-three viromes from different habitats to investigate whether phages harbor ARGs. Our results demonstrate that while human-associated viromes do not or rarely carry ARGs, viromes from non-human sources (e.g. pig feces, raw sewage, and freshwater and marine environments) contain a large reservoir of ARGs, thus pointing out that phages could play a part on the spread of antibiotic resistance. Given this, the role of phages should not be underestimated and it should be considered when designing strategies to tackle the global crisis of antibiotic resistance.

Abundance of antibiotic resistance genes in environmental bacteriophages.

The ecosystem is continuously exposed to a wide variety of antimicrobials through waste effluents, agricultural run-offs and animal-related and anthropogenic activities, which contribute to the spread of antibiotic resistance genes (ARGs). The contamination of ecosystems with ARGs may create increased opportunities for their transfer to naive microbes and eventually lead to entry into the human food chain. Transduction is a significant mechanism of horizontal gene transfer in natural environments, which has traditionally been underestimated as compared to transformation. We explored the presence of ARGs in environmental bacteriophages in order to recognize their contribution in the spread of ARGs in environmental settings. Bacteriophages were isolated against environmental bacterial isolates, purified and bulk cultured. They were characterized, and detection of ARG and intI genes including blaTEM, blaOXA-2, intI1, intI2, intI3, tetA and tetW was carried out by PCR. This study revealed the presence of various genes [tetA (12.7 %), intI1 (10.9 %), intI2 (10.9 %), intI3 (9.1 %), tetW (9.1 %) and blaOXA-2 (3.6 %)] and blaTEM in a significantly higher proportion (30.9 %). blaSHV, blaOXA-1, tetO, tetB, tetG, tetM and tetS were not detected in any of the phages. Soil phages were the most versatile in terms of ARG carriage. Also, the relative abundance of tetA differed significantly vis-à-vis source. The phages from organized farms showed varied ARGs as compared to the unorganized sector, although blaTEM ARG incidences did not differ significantly. The study reflects on the role of phages in dissemination of ARGs in environmental reservoirs, which may provide an early warning system for future clinically relevant resistance mechanisms.

The role of bacteriophages in periodontal health and disease.

The human periodontium health is commonly compromised by chronic inflammatory conditions and has become a major public health concern. Dental plaque, the precursor of periodontal disease, is a complex biofilm consisting mainly of bacteria, but also archaea, protozoa, fungi and viruses. Viruses that specifically infect bacteria - bacteriophages - are most common in the oral cavity. Despite this, their role in the progression of periodontal disease remains poorly explored. This review aims to summarize how bacteriophages interact with the oral microbiota, their ability to increase bacterial virulence and mediate the transfer of resistance genes and suggests how bacteriophages can be used as an alternative to the current periodontal disease therapies.

Healthy human gut phageome

The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.