Pub Date : 2016-01-01DOI: 10.1080/21597081.2016.1157666
Peter G Stockley, Simon J White, Eric Dykeman, Iain Manfield, Ottar Rolfsson, Nikesh Patel, Richard Bingham, Amy Barker, Emma Wroblewski, Rebecca Chandler-Bostock, Eva U Weiß, Neil A Ranson, Roman Tuma, Reidun Twarock
Using RNA-coat protein crosslinking we have shown that the principal RNA recognition surface on the interior of infectious MS2 virions overlaps with the known peptides that bind the high affinity translational operator, TR, within the phage genome. The data also reveal the sequences of genomic fragments in contact with the coat protein shell. These show remarkable overlap with previous predictions based on the hypothesis that virion assembly is mediated by multiple sequences-specific contacts at RNA sites termed Packaging Signals (PSs). These PSs are variations on the TR stem-loop sequence and secondary structure. They act co-operatively to regulate the dominant assembly pathway and ensure cognate RNA encapsidation. In MS2, they also trigger conformational change in the dimeric capsomere creating the A/B quasi-conformer, 60 of which are needed to complete the T=3 capsid. This is the most compelling demonstration to date that this ssRNA virus, and by implications potentially very many of them, assemble via a PS-mediated assembly mechanism.
{"title":"Bacteriophage MS2 genomic RNA encodes an assembly instruction manual for its capsid.","authors":"Peter G Stockley, Simon J White, Eric Dykeman, Iain Manfield, Ottar Rolfsson, Nikesh Patel, Richard Bingham, Amy Barker, Emma Wroblewski, Rebecca Chandler-Bostock, Eva U Weiß, Neil A Ranson, Roman Tuma, Reidun Twarock","doi":"10.1080/21597081.2016.1157666","DOIUrl":"https://doi.org/10.1080/21597081.2016.1157666","url":null,"abstract":"<p><p>Using RNA-coat protein crosslinking we have shown that the principal RNA recognition surface on the interior of infectious MS2 virions overlaps with the known peptides that bind the high affinity translational operator, TR, within the phage genome. The data also reveal the sequences of genomic fragments in contact with the coat protein shell. These show remarkable overlap with previous predictions based on the hypothesis that virion assembly is mediated by multiple sequences-specific contacts at RNA sites termed Packaging Signals (PSs). These PSs are variations on the TR stem-loop sequence and secondary structure. They act co-operatively to regulate the dominant assembly pathway and ensure cognate RNA encapsidation. In MS2, they also trigger conformational change in the dimeric capsomere creating the A/B quasi-conformer, 60 of which are needed to complete the <i>T</i>=3 capsid. This is the most compelling demonstration to date that this ssRNA virus, and by implications potentially very many of them, assemble via a PS-mediated assembly mechanism.</p>","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"6 1","pages":"e1157666"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21597081.2016.1157666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9147322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-10-27DOI: 10.1080/21597081.2015.1093065
C. Georgopoulos
I was born in a small village near Olympia, on the western coast of Peloponnese, Greece, destined to become a farmer like my father and his father before him. However, WWII changed the course of my life in a profound way. The occupying Italian and German forces confiscated many of the farmers’ crops to feed their troops. Later, angered by the continuous Greek armed resistance, they began to burn the farmers’ fields in retaliation. As a consequence, my frustrated father decided to relocate our small family to Athens, taking advantage of the Red Cross distribution of Canadian wheat to the starving Greeks. Thus, my siblings and I grew up in the heart of the Athens slums full of excountry folk like us. The Greek misery continued even after WWII, due to the equally devastating Greek civil war, pitting the communists against the conservatives who were supported by the British and Americans, and lasting until 1949. When I was 8 y old, my father became a green grocer, selling his vegetables in a small stall in the central Athens market. I spent all of my after-school hours and all day Saturday helping my father in his business. At that time, and until 1959, Greece used the old Turkish “oka” as a mass standard (a remnant of the 400-year occupation of Greece by the Ottoman Empire). An oka was divided into 400 drams, a dram being equivalent to 3.2 g today. To further complicate things, an oka was divided into =2, =4, 1/8, 1/10, and 1/25 fractions. My task was not only to weigh the buyer’s groceries using the appropriate weight standards, but also to determine the price based on their weight. Because speed meant more grocery sales, I quickly became proficient in addition, subtraction, multiplication and division. This mastery of “baby math” at a relatively young age gave me confidence in my abilities, and later enabled me to win a competition, thereby earning me a full scholarship at Athens College High School, the best private high school in Greece. At Athens College, one of my favorite professors was Tom Richardson, who was a Fulbright scholar and a graduate of Amherst College in Massachusetts. Richardson was my chemistry professor, a knowledgeable and effective teacher, who instilled in me a passion for doing exact, experimental science. Based mostly on his recommendation, I was awarded a full scholarship as an undergraduate at Amherst. Although I majored in physics at Amherst College, I worked throughout my undergraduate years, including summers, as a laboratory assistant to retired biology professor Harold Henry Plough, in order to earn pocket money and to support myself during school recesses. Plough was a multifaceted scientist. He obtained his PhD degree in 1917 at Columbia University working in the Drosophila lab of T. H. Morgan. Plough’s scientific life was closely interwoven with that of Hermann “Joe” Muller, a fellow graduate student in the Morgan laboratory. According to Plough, who was one of the few who befriended him, Muller was as brilliant
{"title":"How WWII and the old Turkish mass standard led a Greek to a scientific career","authors":"C. Georgopoulos","doi":"10.1080/21597081.2015.1093065","DOIUrl":"https://doi.org/10.1080/21597081.2015.1093065","url":null,"abstract":"I was born in a small village near Olympia, on the western coast of Peloponnese, Greece, destined to become a farmer like my father and his father before him. However, WWII changed the course of my life in a profound way. The occupying Italian and German forces confiscated many of the farmers’ crops to feed their troops. Later, angered by the continuous Greek armed resistance, they began to burn the farmers’ fields in retaliation. As a consequence, my frustrated father decided to relocate our small family to Athens, taking advantage of the Red Cross distribution of Canadian wheat to the starving Greeks. Thus, my siblings and I grew up in the heart of the Athens slums full of excountry folk like us. The Greek misery continued even after WWII, due to the equally devastating Greek civil war, pitting the communists against the conservatives who were supported by the British and Americans, and lasting until 1949. When I was 8 y old, my father became a green grocer, selling his vegetables in a small stall in the central Athens market. I spent all of my after-school hours and all day Saturday helping my father in his business. At that time, and until 1959, Greece used the old Turkish “oka” as a mass standard (a remnant of the 400-year occupation of Greece by the Ottoman Empire). An oka was divided into 400 drams, a dram being equivalent to 3.2 g today. To further complicate things, an oka was divided into =2, =4, 1/8, 1/10, and 1/25 fractions. My task was not only to weigh the buyer’s groceries using the appropriate weight standards, but also to determine the price based on their weight. Because speed meant more grocery sales, I quickly became proficient in addition, subtraction, multiplication and division. This mastery of “baby math” at a relatively young age gave me confidence in my abilities, and later enabled me to win a competition, thereby earning me a full scholarship at Athens College High School, the best private high school in Greece. At Athens College, one of my favorite professors was Tom Richardson, who was a Fulbright scholar and a graduate of Amherst College in Massachusetts. Richardson was my chemistry professor, a knowledgeable and effective teacher, who instilled in me a passion for doing exact, experimental science. Based mostly on his recommendation, I was awarded a full scholarship as an undergraduate at Amherst. Although I majored in physics at Amherst College, I worked throughout my undergraduate years, including summers, as a laboratory assistant to retired biology professor Harold Henry Plough, in order to earn pocket money and to support myself during school recesses. Plough was a multifaceted scientist. He obtained his PhD degree in 1917 at Columbia University working in the Drosophila lab of T. H. Morgan. Plough’s scientific life was closely interwoven with that of Hermann “Joe” Muller, a fellow graduate student in the Morgan laboratory. According to Plough, who was one of the few who befriended him, Muller was as brilliant ","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85787714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-08-28DOI: 10.1080/21597081.2015.1088124
V. Mai, M. Ukhanova, M. Reinhard, Manrong Li, A. Sulakvelidze
We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal Shigella counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with Shigella sonnei strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic Shigella bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTM treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. Shigella phages may be therapeutically effective in a “classical phage therapy” approach, at least during the early stages after Shigella ingestion. Oral prophylactic “phagebiotic” administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota.
{"title":"Bacteriophage administration significantly reduces Shigella colonization and shedding by Shigella-challenged mice without deleterious side effects and distortions in the gut microbiota","authors":"V. Mai, M. Ukhanova, M. Reinhard, Manrong Li, A. Sulakvelidze","doi":"10.1080/21597081.2015.1088124","DOIUrl":"https://doi.org/10.1080/21597081.2015.1088124","url":null,"abstract":"We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal Shigella counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with Shigella sonnei strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic Shigella bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTM treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. Shigella phages may be therapeutically effective in a “classical phage therapy” approach, at least during the early stages after Shigella ingestion. Oral prophylactic “phagebiotic” administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81133147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-08-25DOI: 10.1080/21597081.2015.1086500
J. Davison
Summary Coliphage T5 injects its DNA in 2 steps: the first step transfer (FST) region 7.9% is injected and its genes are expressed and only then does the remainder (second step transfer, SST) of its DNA enter the cell. In the FST region, only 2 essential genes (A1 and A2) have been identified and a third (dmp) non-essential gene codes for a deoxyribonucleotide 5′ monophosphatase. Thirteen additional putative ORFs are present in the FST region. Numerous properties have been attributed to FST region, including SST, host DNA degradation, inhibition of host RNA and protein synthesis, restriction insensitivity and protection of T5 DNA. These effects do not occur following infection with an A1 mutant. The A2 gene seems only to be involved in SST transfer. This is puzzling since there are more seemingly unrelated effects than there are essential genes to accomplish them and it is possible that some important genes were not identified. This review attempts to analyze these problems that were first identified in the 1970–80 s. In particular, an attempt is made to determine which potential ORFs are conserved in evolution (and thus likely to be important); by comparing T5 to 10 newly isolated and completely sequenced T5-like phages. A similar approach is used to identify conserved repeats, inverted repeats and palindromes that occur in all T5-like phages in the region containing the injection stop signal (iss) and the terminase substrate. Finally, an attempt is made to re-analyze the mechanism whereby T5 protects itself from the enzymes that degrade host DNA, from the RecBCD nuclease and from restriction enzymes. For all of these FST effects new hypotheses and possible new genetic and biochemical approaches are envisaged.
{"title":"Pre-early functions of bacteriophage T5 and its relatives","authors":"J. Davison","doi":"10.1080/21597081.2015.1086500","DOIUrl":"https://doi.org/10.1080/21597081.2015.1086500","url":null,"abstract":"Summary Coliphage T5 injects its DNA in 2 steps: the first step transfer (FST) region 7.9% is injected and its genes are expressed and only then does the remainder (second step transfer, SST) of its DNA enter the cell. In the FST region, only 2 essential genes (A1 and A2) have been identified and a third (dmp) non-essential gene codes for a deoxyribonucleotide 5′ monophosphatase. Thirteen additional putative ORFs are present in the FST region. Numerous properties have been attributed to FST region, including SST, host DNA degradation, inhibition of host RNA and protein synthesis, restriction insensitivity and protection of T5 DNA. These effects do not occur following infection with an A1 mutant. The A2 gene seems only to be involved in SST transfer. This is puzzling since there are more seemingly unrelated effects than there are essential genes to accomplish them and it is possible that some important genes were not identified. This review attempts to analyze these problems that were first identified in the 1970–80 s. In particular, an attempt is made to determine which potential ORFs are conserved in evolution (and thus likely to be important); by comparing T5 to 10 newly isolated and completely sequenced T5-like phages. A similar approach is used to identify conserved repeats, inverted repeats and palindromes that occur in all T5-like phages in the region containing the injection stop signal (iss) and the terminase substrate. Finally, an attempt is made to re-analyze the mechanism whereby T5 protects itself from the enzymes that degrade host DNA, from the RecBCD nuclease and from restriction enzymes. For all of these FST effects new hypotheses and possible new genetic and biochemical approaches are envisaged.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80844187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-08-18DOI: 10.1080/21597081.2015.1084073
W. Pope, G. Hatfull
Bacteriophages are the dark matter of the biological universe: the population is vast and replete with novel genes whose function is unknown. The genomic insights such as the mosaic architecture gleaned from perhaps 2,000 currently sequenced bacteriophage genomes is far from representative of the total number phage particles in the biosphere - about 10ˆ31. The recent comparative analysis of 627 mycobacteriophages isolated on Mycobacterium smegmatis mc2 155 is the most extensive examination yet in pursuit of this question.
{"title":"Adding pieces to the puzzle: New insights into bacteriophage diversity from integrated research-education programs","authors":"W. Pope, G. Hatfull","doi":"10.1080/21597081.2015.1084073","DOIUrl":"https://doi.org/10.1080/21597081.2015.1084073","url":null,"abstract":"Bacteriophages are the dark matter of the biological universe: the population is vast and replete with novel genes whose function is unknown. The genomic insights such as the mosaic architecture gleaned from perhaps 2,000 currently sequenced bacteriophage genomes is far from representative of the total number phage particles in the biosphere - about 10ˆ31. The recent comparative analysis of 627 mycobacteriophages isolated on Mycobacterium smegmatis mc2 155 is the most extensive examination yet in pursuit of this question.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"251 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72962453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-08-12DOI: 10.1080/21597081.2015.1080787
L. Leblanc, S. Nezami, Diane G. Yost, Philippos K. Tsourkas, P. Amy
Paenibacillus larvae is the causative agent of American foulbrood (AFB) disease which affects early larval stages during honeybee development. Due to its virulence, transmissibility, capacity to develop antibiotic resistance, and the inherent resilience of its endospores, Paenibacillus larvae is extremely difficult to eradicate from infected hives which often must be burned. AFB contributes to the worldwide decline of honeybee populations, which are crucial for pollination and the food supply. We have isolated a novel bacteriophage lysin, PlyPalA, from the genome of a novel Paenibacillus larvae bacteriophage originally extracted from an environmental sample. PlyPalA has an N-terminal N-acetylmuramoyl-L-alanine amidase catalytic domain and possesses lytic activity against infectious strains of Paenibacillus larvae without harming commensal bacteria known to compose the honeybee larval microbiota. A single dose of PlyPalA rescued 75% of larvae infected with endospores, showing that it represents a powerful tool for future treatment of AFB. This represents the first time that lysins have been tested for therapeutic use in invertebrates.
{"title":"Isolation and characterization of a novel phage lysin active against Paenibacillus larvae, a honeybee pathogen","authors":"L. Leblanc, S. Nezami, Diane G. Yost, Philippos K. Tsourkas, P. Amy","doi":"10.1080/21597081.2015.1080787","DOIUrl":"https://doi.org/10.1080/21597081.2015.1080787","url":null,"abstract":"Paenibacillus larvae is the causative agent of American foulbrood (AFB) disease which affects early larval stages during honeybee development. Due to its virulence, transmissibility, capacity to develop antibiotic resistance, and the inherent resilience of its endospores, Paenibacillus larvae is extremely difficult to eradicate from infected hives which often must be burned. AFB contributes to the worldwide decline of honeybee populations, which are crucial for pollination and the food supply. We have isolated a novel bacteriophage lysin, PlyPalA, from the genome of a novel Paenibacillus larvae bacteriophage originally extracted from an environmental sample. PlyPalA has an N-terminal N-acetylmuramoyl-L-alanine amidase catalytic domain and possesses lytic activity against infectious strains of Paenibacillus larvae without harming commensal bacteria known to compose the honeybee larval microbiota. A single dose of PlyPalA rescued 75% of larvae infected with endospores, showing that it represents a powerful tool for future treatment of AFB. This represents the first time that lysins have been tested for therapeutic use in invertebrates.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"238 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82877873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-07-24eCollection Date: 2015-07-01DOI: 10.1080/21597081.2015.1074329
A V Aleshkin, E O Rubalskii, N V Volozhantsev, V V Verevkin, E A Svetoch, I A Kiseleva, S S Bochkareva, O Yu Borisova, A V Popova, A G Bogun, S S Afanas'ev
Traveler's diarrhea (TD) is caused by Escherichia coli in 30% of cases. We have developed a phage cocktail for prophylaxis of TD caused by E.coli, Shigella flexneri, Shigella sonnei, Salmonella enterica, Listeria monocytogenes or Staphylococcus aureus, and investigated its effectiveness against infection caused by the non-pathogenic Lac (-) strain of E.coli K12 C600 in animal and human trials. On the 6th day of both animal and human trials E. coli K12 C600 strain was detected in titer of 104 CFU/g of mice feces and 106 CFU/g of human feces in the control (untreated) groups, while it was not detected in the samples of either of the study (phage-treated) groups. These results have great significance because the original coliphages included in the cocktail have a broad host-range including ETEC, EAEC and EHEC strains which cause severe cases of TD.
{"title":"A small-scale experiment of using phage-based probiotic dietary supplement for prevention of E. coli traveler's diarrhea.","authors":"A V Aleshkin, E O Rubalskii, N V Volozhantsev, V V Verevkin, E A Svetoch, I A Kiseleva, S S Bochkareva, O Yu Borisova, A V Popova, A G Bogun, S S Afanas'ev","doi":"10.1080/21597081.2015.1074329","DOIUrl":"https://doi.org/10.1080/21597081.2015.1074329","url":null,"abstract":"<p><p>Traveler's diarrhea (TD) is caused by Escherichia coli in 30% of cases. We have developed a phage cocktail for prophylaxis of TD caused by E.coli, Shigella flexneri, Shigella sonnei, Salmonella enterica, Listeria monocytogenes or Staphylococcus aureus, and investigated its effectiveness against infection caused by the non-pathogenic Lac (-) strain of E.coli K12 C600 in animal and human trials. On the 6th day of both animal and human trials E. coli K12 C600 strain was detected in titer of 10<sup>4</sup> CFU/g of mice feces and 10<sup>6</sup> CFU/g of human feces in the control (untreated) groups, while it was not detected in the samples of either of the study (phage-treated) groups. These results have great significance because the original coliphages included in the cocktail have a broad host-range including ETEC, EAEC and EHEC strains which cause severe cases of TD.</p>","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"5 3","pages":"e1074329"},"PeriodicalIF":0.0,"publicationDate":"2015-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21597081.2015.1074329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34147527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-06-25eCollection Date: 2015-07-01DOI: 10.1080/21597081.2015.1050154
Fred Eiserling
My love for science began with a trip at age 12 to Los Angeles’ Griffith Observatory. My father, a professional photographer, helped me construct a small telescope. I first saw Jupiter’s moons, and was captivated by their changing positions. That telescope was not much better than Galileo’s, but it still was exciting. I later made my own Newtonian mirror, went to astronomy meetings, met Edwin Hubble and spend time with Thomas Cragg at Mount Wilson Observatory, all before age 16. As an undergraduate at UCLA in 1955 I wanted to major in astronomy, but was told by the faculty that there were no jobs in astronomy and that UCLA did not even have a PhD program. Still, I took courses in astronomy. In one course, from Prof. George Abell, we plotted the 1957 orbit of a new satellite called Sputnik. Little did we know then that in 5 years there would be plenty of jobs in astronomy. Discouraged from astronomy I switched to Biology and then to Bacteriology. I loved optics, microscopes and imaging and was able to get a part-time undergraduate job in the laboratory of Fritiof Sjostrand who had just come from Sweden to UCLA as professor of zoology. There were 2 electron microscopes, and their technology was as exciting to me as big telescopes. I later decided to stay on as a graduate student in bacteriology, and did my first phage experiments with Professor W. R. Romig. He had a soft southern accent, was very modest, and is not as well recognized in the bacteriophage community as he should be. He was among the very first to show that purified DNA extracted from a phage (SPO1) was infectious when used to transform Bacillus subtilis Bob Romig was an excellent teacher and mentor. He spent a great deal of time with each graduate student, gently pointing out missing control experiments and showing us how to design better experimental protocols. The most exciting part of this graduate experience was linking my phage experiments to electron microscopy. By now I was allowed to use the electron microscopes in the Sjostrand lab, and learned to do negative staining of phage. I discovered that by disrupting bacterial DNA replication by UV irradiation, or Mitomycin C treatment that every variety of Bacillus I examined produced either whole phage or phage parts after these treatments. I concluded in my PhD thesis, rather boldly, that bacterial genomes were all made in part from bacteriophage genes, which was a somewhat novel idea in 1962. I was incredibly fortunate to be able to work in the Sjostrand lab. One day, Professor Sjostrand told me one of his visitors needed a tennis partner, and that was to be me. The visitor was Hugh Huxley, and after tennis he showed me how to do negative contrast of macromolecules using uranyl acetate. This was a huge improvement in contrast and resolution. I also learned how to make novel support films containing holes for mounting ultrathin sections of bacteria and to add additional contrast with uranium salts. Professor Sjostrand was interes
{"title":"Life in science.","authors":"Fred Eiserling","doi":"10.1080/21597081.2015.1050154","DOIUrl":"https://doi.org/10.1080/21597081.2015.1050154","url":null,"abstract":"My love for science began with a trip at age 12 to Los Angeles’ Griffith Observatory. My father, a professional photographer, helped me construct a small telescope. I first saw Jupiter’s moons, and was captivated by their changing positions. That telescope was not much better than Galileo’s, but it still was exciting. I later made my own Newtonian mirror, went to astronomy meetings, met Edwin Hubble and spend time with Thomas Cragg at Mount Wilson Observatory, all before age 16. As an undergraduate at UCLA in 1955 I wanted to major in astronomy, but was told by the faculty that there were no jobs in astronomy and that UCLA did not even have a PhD program. Still, I took courses in astronomy. In one course, from Prof. George Abell, we plotted the 1957 orbit of a new satellite called Sputnik. Little did we know then that in 5 years there would be plenty of jobs in astronomy. Discouraged from astronomy I switched to Biology and then to Bacteriology. I loved optics, microscopes and imaging and was able to get a part-time undergraduate job in the laboratory of Fritiof Sjostrand who had just come from Sweden to UCLA as professor of zoology. There were 2 electron microscopes, and their technology was as exciting to me as big telescopes. I later decided to stay on as a graduate student in bacteriology, and did my first phage experiments with Professor W. R. Romig. He had a soft southern accent, was very modest, and is not as well recognized in the bacteriophage community as he should be. He was among the very first to show that purified DNA extracted from a phage (SPO1) was infectious when used to transform Bacillus subtilis Bob Romig was an excellent teacher and mentor. He spent a great deal of time with each graduate student, gently pointing out missing control experiments and showing us how to design better experimental protocols. The most exciting part of this graduate experience was linking my phage experiments to electron microscopy. By now I was allowed to use the electron microscopes in the Sjostrand lab, and learned to do negative staining of phage. I discovered that by disrupting bacterial DNA replication by UV irradiation, or Mitomycin C treatment that every variety of Bacillus I examined produced either whole phage or phage parts after these treatments. I concluded in my PhD thesis, rather boldly, that bacterial genomes were all made in part from bacteriophage genes, which was a somewhat novel idea in 1962. I was incredibly fortunate to be able to work in the Sjostrand lab. One day, Professor Sjostrand told me one of his visitors needed a tennis partner, and that was to be me. The visitor was Hugh Huxley, and after tennis he showed me how to do negative contrast of macromolecules using uranyl acetate. This was a huge improvement in contrast and resolution. I also learned how to make novel support films containing holes for mounting ultrathin sections of bacteria and to add additional contrast with uranium salts. Professor Sjostrand was interes","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"5 3","pages":"e1050154"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21597081.2015.1050154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34066294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-06-24eCollection Date: 2015-07-01DOI: 10.1080/21597081.2015.1062588
Jelena Guzina, Marko Djordjevic
Current approach to understanding bacteriophage transcription strategies during infection includes a combination of experimental and bioinformatics approaches, which is often time and resource consuming. Given the exponentially growing number of sequenced bacteriophage genomes, it becomes sensible asking to what extent one can understand bacteriophage transcription by using bioinformatics methods alone. We here argue that a suitable choice of computational methods may provide a highly efficient first-line approach for underst-anding bacteriophage transcription.
{"title":"Bioinformatics as a first-line approach for understanding bacteriophage transcription.","authors":"Jelena Guzina, Marko Djordjevic","doi":"10.1080/21597081.2015.1062588","DOIUrl":"https://doi.org/10.1080/21597081.2015.1062588","url":null,"abstract":"<p><p>Current approach to understanding bacteriophage transcription strategies during infection includes a combination of experimental and bioinformatics approaches, which is often time and resource consuming. Given the exponentially growing number of sequenced bacteriophage genomes, it becomes sensible asking to what extent one can understand bacteriophage transcription by using bioinformatics methods alone. We here argue that a suitable choice of computational methods may provide a highly efficient first-line approach for underst-anding bacteriophage transcription.</p>","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"5 3","pages":"e1062588"},"PeriodicalIF":0.0,"publicationDate":"2015-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21597081.2015.1062588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34066296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-06-23eCollection Date: 2015-07-01DOI: 10.1080/21597081.2015.1062590
Dwayne R Roach, David M Donovan
Antibiotics have the remarkable power to control bacterial infections. Unfortunately, widespread use, whether regarded as prudent or not, has favored the emergence and persistence of antibiotic resistant strains of human pathogenic bacteria, resulting in a global health threat. Bacteriophages (phages) are parasites that invade the cells of virtually all known bacteria. Phages reproduce by utilizing the host cell's machinery to replicate viral proteins and genomic material, generally damaging and killing the cell in the process. Thus, phage can be exploited therapeutically as bacteriolytic agents against bacteria. Furthermore, understanding of the molecular processes involved in the viral life cycle, particularly the entry and cell lysis steps, has led to the development of viral proteins as antibacterial agents. Here we review the current preclinical state of using phage-derived endolysins, virion-associated peptidoglycan hydrolases, polysaccharide depolymerases, and holins for the treatment of bacterial infection. The scope of this review is a focus on the viral proteins that have been assessed for protective effects against human pathogenic bacteria in animal models of infection and disease.
{"title":"Antimicrobial bacteriophage-derived proteins and therapeutic applications.","authors":"Dwayne R Roach, David M Donovan","doi":"10.1080/21597081.2015.1062590","DOIUrl":"https://doi.org/10.1080/21597081.2015.1062590","url":null,"abstract":"<p><p>Antibiotics have the remarkable power to control bacterial infections. Unfortunately, widespread use, whether regarded as prudent or not, has favored the emergence and persistence of antibiotic resistant strains of human pathogenic bacteria, resulting in a global health threat. Bacteriophages (phages) are parasites that invade the cells of virtually all known bacteria. Phages reproduce by utilizing the host cell's machinery to replicate viral proteins and genomic material, generally damaging and killing the cell in the process. Thus, phage can be exploited therapeutically as bacteriolytic agents against bacteria. Furthermore, understanding of the molecular processes involved in the viral life cycle, particularly the entry and cell lysis steps, has led to the development of viral proteins as antibacterial agents. Here we review the current preclinical state of using phage-derived endolysins, virion-associated peptidoglycan hydrolases, polysaccharide depolymerases, and holins for the treatment of bacterial infection. The scope of this review is a focus on the viral proteins that have been assessed for protective effects against human pathogenic bacteria in animal models of infection and disease.</p>","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":"5 3","pages":"e1062590"},"PeriodicalIF":0.0,"publicationDate":"2015-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21597081.2015.1062590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34067320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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