Pub Date : 2016-10-21eCollection Date: 2016-01-01DOI: 10.1080/21597081.2016.1251379
A V Aleshkin, O N Ershova, N V Volozhantsev, E A Svetoch, A V Popova, E O Rubalskii, A I Borzilov, V A Aleshkin, S S Afanas'ev, A V Karaulov, K M Galimzyanov, O V Rubalsky, S S Bochkareva
We have developed a phagebiotic composition using 8 virulent bacteriophages (2 strains of each species) which are able to lyse Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. The unique character of the developed composition is ensured by particular properties of each bacteriophage comprising the preparation, including their range of lytic activity toward specific bacterial pathogens, morphology of their plaques, cycle of their development, restriction profile of their DNAs, specificity of their genomes (based on complete genome sequencing), and other properties. The preparation did not produce any signs of acute or chronic intoxication in the experimental animals. Therapeutic and prophylactic efficiency of the phagebiotic composition was demonstrated in the prevention and treatment of the experimental acute K. pneumoniae infection in mice. The investigations have shown that the preparation possesses a high therapeutic efficiency and is highly competitive with ciprofloxacin which is very effective against the infective strain K. pneumoniae. Our small-scale clinical trial was aimed to evaluate therapeutic effectiveness of the phagebiotic composition in an epidemiological emergency situation in an intensive care unit, caused by multi-resistant strains of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Seventy nine per cent of the initial samples from 14 patients' endotracheal aspirate, blood and urine were contaminated. Twenty-four hours after the 3-day phage therapy (20 ml of cocktail at a titer for each phage 108 pfu/ml were introduced intragastrically through a tube once a day) contamination level dropped to 21%. Hence the obtained results enabled us to create a new phagebiotic composition that may be used as an alternative to antibiotics to treat these healthcare-associated infections.
{"title":"Phagebiotics in treatment and prophylaxis of healthcare-associated infections.","authors":"A V Aleshkin, O N Ershova, N V Volozhantsev, E A Svetoch, A V Popova, E O Rubalskii, A I Borzilov, V A Aleshkin, S S Afanas'ev, A V Karaulov, K M Galimzyanov, O V Rubalsky, S S Bochkareva","doi":"10.1080/21597081.2016.1251379","DOIUrl":"10.1080/21597081.2016.1251379","url":null,"abstract":"<p><p>We have developed a phagebiotic composition using 8 virulent bacteriophages (2 strains of each species) which are able to lyse <i>Acinetobacter baumannii</i>, <i>Klebsiella pneumoniae</i>, <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i>. The unique character of the developed composition is ensured by particular properties of each bacteriophage comprising the preparation, including their range of lytic activity toward specific bacterial pathogens, morphology of their plaques, cycle of their development, restriction profile of their DNAs, specificity of their genomes (based on complete genome sequencing), and other properties. The preparation did not produce any signs of acute or chronic intoxication in the experimental animals. Therapeutic and prophylactic efficiency of the phagebiotic composition was demonstrated in the prevention and treatment of the experimental acute <i>K. pneumoniae</i> infection in mice. The investigations have shown that the preparation possesses a high therapeutic efficiency and is highly competitive with ciprofloxacin which is very effective against the infective strain <i>K. pneumoniae</i>. Our small-scale clinical trial was aimed to evaluate therapeutic effectiveness of the phagebiotic composition in an epidemiological emergency situation in an intensive care unit, caused by multi-resistant strains of <i>Acinetobacter baumannii</i>, <i>Klebsiella pneumoniae</i> and <i>Pseudomonas aeruginosa</i>. Seventy nine per cent of the initial samples from 14 patients' endotracheal aspirate, blood and urine were contaminated. Twenty-four hours after the 3-day phage therapy (20 ml of cocktail at a titer for each phage 10<sup>8</sup> pfu/ml were introduced intragastrically through a tube once a day) contamination level dropped to 21%. Hence the obtained results enabled us to create a new phagebiotic composition that may be used as an alternative to antibiotics to treat these healthcare-associated infections.</p>","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88135284","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 : 2016-10-01DOI: 10.1080/21597081.2016.1268664
P. Serwer, E. Wright
ABSTRACT We argue that a paradigm shift is needed in the analysis of phage DNA packaging. We then test a prediction of the following paradigm shift-engendering hypothesis. The motor of phage DNA packaging has two cycles: (1) the well-known packaging ATPase-driven (type 1) cycle and (2) a proposed back-up, shell expansion/contraction-driven (type 2) cycle that reverses type 1 cycle stalls by expelling accidentally packaged non-DNA molecules. We test the prediction that increasing the cellular concentration of all macromolecules will cause packaging-active capsids to divert to states of hyper-expansion and contraction. We use a directed evolution-derived, 3-site phage T3 mutant, adapted to propagation in concentrated bacterial cytoplasm. We find this prediction correct while discovering novel T3 capsids previously obscure.
{"title":"Testing a proposed paradigm shift in analysis of phage DNA packaging","authors":"P. Serwer, E. Wright","doi":"10.1080/21597081.2016.1268664","DOIUrl":"https://doi.org/10.1080/21597081.2016.1268664","url":null,"abstract":"ABSTRACT We argue that a paradigm shift is needed in the analysis of phage DNA packaging. We then test a prediction of the following paradigm shift-engendering hypothesis. The motor of phage DNA packaging has two cycles: (1) the well-known packaging ATPase-driven (type 1) cycle and (2) a proposed back-up, shell expansion/contraction-driven (type 2) cycle that reverses type 1 cycle stalls by expelling accidentally packaged non-DNA molecules. We test the prediction that increasing the cellular concentration of all macromolecules will cause packaging-active capsids to divert to states of hyper-expansion and contraction. We use a directed evolution-derived, 3-site phage T3 mutant, adapted to propagation in concentrated bacterial cytoplasm. We find this prediction correct while discovering novel T3 capsids previously obscure.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72674028","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 : 2016-10-01DOI: 10.1080/21597081.2016.1251381
R. Stevens, Hongming Zhang, Chaiwing Hsiao, S. Kachlany, Eduardo M. B. Tinoco, Jessica DePew, D. Fouts
ABSTRACT φEf11, a temperate Siphoviridae bacteriophage, was isolated by induction from a root canal isolate of Enterococcus faecalis. Sequence analysis suggested that the φEf11 genome included a contiguous 8 gene module whose function was related to head structure assembly and another module of 10 contiguous genes whose products were responsible for tail structure assembly. SDS-PAGE analysis of virions of a φEf11 derivative revealed 11 well-resolved protein bands. To unify the deduced functional gene assignments emanating from the DNA sequence data, with the structural protein analysis of the purified virus, 6 of the SDS-PAGE bands were subjected to mass spectrometry analysis. 5 of the 6 protein bands analyzed by mass spectrometry displayed identical amino acid sequences to those predicted to be specified by 4 of the ORFs identified in the φEf11 genome. These included: ORF8 (predicted scaffold protein), ORF10 (predicted major head protein), ORF15 (predicted major tail protein), and ORF23 (presumptive antireceptor).
{"title":"Structural proteins of Enterococcus faecalis bacteriophage ϕEf11","authors":"R. Stevens, Hongming Zhang, Chaiwing Hsiao, S. Kachlany, Eduardo M. B. Tinoco, Jessica DePew, D. Fouts","doi":"10.1080/21597081.2016.1251381","DOIUrl":"https://doi.org/10.1080/21597081.2016.1251381","url":null,"abstract":"ABSTRACT φEf11, a temperate Siphoviridae bacteriophage, was isolated by induction from a root canal isolate of Enterococcus faecalis. Sequence analysis suggested that the φEf11 genome included a contiguous 8 gene module whose function was related to head structure assembly and another module of 10 contiguous genes whose products were responsible for tail structure assembly. SDS-PAGE analysis of virions of a φEf11 derivative revealed 11 well-resolved protein bands. To unify the deduced functional gene assignments emanating from the DNA sequence data, with the structural protein analysis of the purified virus, 6 of the SDS-PAGE bands were subjected to mass spectrometry analysis. 5 of the 6 protein bands analyzed by mass spectrometry displayed identical amino acid sequences to those predicted to be specified by 4 of the ORFs identified in the φEf11 genome. These included: ORF8 (predicted scaffold protein), ORF10 (predicted major head protein), ORF15 (predicted major tail protein), and ORF23 (presumptive antireceptor).","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90045027","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 : 2016-10-01DOI: 10.1080/21597081.2016.1271250
M. Salas
I was born in Canero, Spain, a very small village in the north coast of Asturias. When I was one year old, my parents moved to Gij on, also in Asturias, where I spent my childhood and early youth. There, I attended the school and obtained the baccalaureate title in 1954. Since I wanted to pursue a university career, I had to spend one year doing the so-called pre-university studies and to decide whether I wanted to follow a scientific or a humanistic career. I choose to go into science. At the end of the year I had to decide which specific career I wanted to follow. I doubted between medicine and chemistry. Since medicine was not available at Oviedo University, close to Gij on, I decided to go to Madrid University to follow a course common for both careers. Finally, I decided to study chemistry. In the third year we studied organic chemistry, and I enjoyed very much the long hours we spent in the laboratory. I thought that, in the future, I would like to do research in organic chemistry. But that was not the case. In the summer of 1958, when I had finished my third year of chemistry, I went to Gij on to spend the holidays, and I was very lucky to meet Severo Ochoa, which had a decisive influence on my future. I attended a conference he gave about his work and I was fascinated by his talk. Since my father was a good friend of Ochoa, besides being cousins in law, I had the chance to talk to him about my future. I had not yet studied biochemistry and he promised to send me a biochemistry book. I was very excited when I received the book General Biochemistry by Fruton and Simmonds, dedicated by Severo Ochoa. When I finished my chemistry studies I had decided to dedicate myself to biochemistry. Ochoa advised me to do the Ph.D. Thesis in Madrid with Alberto Sols, an excellent biochemist, who had been trained with Carl and Gerty Cori at the Washington University School of Medicine in St. Louis. Then, I could go to Ochoa’s laboratory at New York University (NYU) School of Medicine for a postdoctoral training. Ochoa wrote me a reference letter for Alberto Sols who accepted me, even if I was a woman, since he could not refuse a request made by Severo Ochoa who had already obtained the Nobel Prize. Thus, in January 1961, I started my Ph.D. Thesis working on carbohydrate metabolism, mainly on glucose-phosphate isomerase from yeast. I found that the enzyme has an anomerase-like activity producing the open form of glucose6-phosphate. This was the first finding in my scientific career, something that was very exciting for me. The work was published in the Journal of Biological Chemistry. At the end of my studies in chemistry, I
{"title":"My scientific life","authors":"M. Salas","doi":"10.1080/21597081.2016.1271250","DOIUrl":"https://doi.org/10.1080/21597081.2016.1271250","url":null,"abstract":"I was born in Canero, Spain, a very small village in the north coast of Asturias. When I was one year old, my parents moved to Gij on, also in Asturias, where I spent my childhood and early youth. There, I attended the school and obtained the baccalaureate title in 1954. Since I wanted to pursue a university career, I had to spend one year doing the so-called pre-university studies and to decide whether I wanted to follow a scientific or a humanistic career. I choose to go into science. At the end of the year I had to decide which specific career I wanted to follow. I doubted between medicine and chemistry. Since medicine was not available at Oviedo University, close to Gij on, I decided to go to Madrid University to follow a course common for both careers. Finally, I decided to study chemistry. In the third year we studied organic chemistry, and I enjoyed very much the long hours we spent in the laboratory. I thought that, in the future, I would like to do research in organic chemistry. But that was not the case. In the summer of 1958, when I had finished my third year of chemistry, I went to Gij on to spend the holidays, and I was very lucky to meet Severo Ochoa, which had a decisive influence on my future. I attended a conference he gave about his work and I was fascinated by his talk. Since my father was a good friend of Ochoa, besides being cousins in law, I had the chance to talk to him about my future. I had not yet studied biochemistry and he promised to send me a biochemistry book. I was very excited when I received the book General Biochemistry by Fruton and Simmonds, dedicated by Severo Ochoa. When I finished my chemistry studies I had decided to dedicate myself to biochemistry. Ochoa advised me to do the Ph.D. Thesis in Madrid with Alberto Sols, an excellent biochemist, who had been trained with Carl and Gerty Cori at the Washington University School of Medicine in St. Louis. Then, I could go to Ochoa’s laboratory at New York University (NYU) School of Medicine for a postdoctoral training. Ochoa wrote me a reference letter for Alberto Sols who accepted me, even if I was a woman, since he could not refuse a request made by Severo Ochoa who had already obtained the Nobel Prize. Thus, in January 1961, I started my Ph.D. Thesis working on carbohydrate metabolism, mainly on glucose-phosphate isomerase from yeast. I found that the enzyme has an anomerase-like activity producing the open form of glucose6-phosphate. This was the first finding in my scientific career, something that was very exciting for me. The work was published in the Journal of Biological Chemistry. At the end of my studies in chemistry, I","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89610643","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 : 2016-10-01DOI: 10.1080/21597081.2016.1251380
K. Moelling, F. Broecker
ABSTRACT We have analyzed fecal bacterial and viral communities of a patient with recurrent C. difficile infection (rCDI) who was cured by fecal microbiota transplantation (FMT). The “Zürich Patient” experienced immediate cure and has remained free of symptoms for now over 5 y. Donor-similar bacterial compositions after 4.5 y post-FMT demonstrated sustainable engraftment of donor microbiota predominated by Bacteroidetes and Firmicutes bacteria. Appearance of beneficial species Faecalibacterium prausnitzii and Akkermansia municiphila was detected while disease-related Proteobacteria decreased. Stabilization of the microbiota took longer than expected from the rapidly improving clinical symptoms, suggesting the need for longer-lasting patient observation. The virome was mainly composed of Caudovirales bacteriophages but surprisingly also contained sequences related to a Chlorella giant virus that normally infects green algae not known to inhabitate the human intestine. FMT is highly effective against rCDI and is presently broadening its application to other conditions including inflammatory bowel disease (IBD). Here, we discuss the prospects and challenges of FMT against rCDI and other indications including a focus on bacteriophages.
{"title":"Fecal microbiota transplantation to fight Clostridium difficile infections and other intestinal diseases","authors":"K. Moelling, F. Broecker","doi":"10.1080/21597081.2016.1251380","DOIUrl":"https://doi.org/10.1080/21597081.2016.1251380","url":null,"abstract":"ABSTRACT We have analyzed fecal bacterial and viral communities of a patient with recurrent C. difficile infection (rCDI) who was cured by fecal microbiota transplantation (FMT). The “Zürich Patient” experienced immediate cure and has remained free of symptoms for now over 5 y. Donor-similar bacterial compositions after 4.5 y post-FMT demonstrated sustainable engraftment of donor microbiota predominated by Bacteroidetes and Firmicutes bacteria. Appearance of beneficial species Faecalibacterium prausnitzii and Akkermansia municiphila was detected while disease-related Proteobacteria decreased. Stabilization of the microbiota took longer than expected from the rapidly improving clinical symptoms, suggesting the need for longer-lasting patient observation. The virome was mainly composed of Caudovirales bacteriophages but surprisingly also contained sequences related to a Chlorella giant virus that normally infects green algae not known to inhabitate the human intestine. FMT is highly effective against rCDI and is presently broadening its application to other conditions including inflammatory bowel disease (IBD). Here, we discuss the prospects and challenges of FMT against rCDI and other indications including a focus on bacteriophages.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73409555","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 : 2016-10-01DOI: 10.1080/21597081.2016.1270090
W. Summers
ABSTRACT The discovery of bacteriophage one century ago by the French-Canadian Félix d'Herelle set off controversies as to the nature of bacteriophage as well as over the priority and credit for this discovery. The background and life of d'Herelle reveals a complex, self-taught outsider in science who was strongly influenced by his admiration of Louis Pasteur, but also his attachment to the philosophical positions of early 17th century philosophers, especially Francis Bacon. D'Herelle left substantial unpublished writings on his philosophical musings toward the end of his life.
{"title":"Félix Hubert d'Herelle (1873–1949): History of a scientific mind","authors":"W. Summers","doi":"10.1080/21597081.2016.1270090","DOIUrl":"https://doi.org/10.1080/21597081.2016.1270090","url":null,"abstract":"ABSTRACT The discovery of bacteriophage one century ago by the French-Canadian Félix d'Herelle set off controversies as to the nature of bacteriophage as well as over the priority and credit for this discovery. The background and life of d'Herelle reveals a complex, self-taught outsider in science who was strongly influenced by his admiration of Louis Pasteur, but also his attachment to the philosophical positions of early 17th century philosophers, especially Francis Bacon. D'Herelle left substantial unpublished writings on his philosophical musings toward the end of his life.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74654879","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 : 2016-08-02eCollection Date: 2016-07-01DOI: 10.1080/21597081.2016.1218411
Tushar Suvra Bhowmick, Mayukh Das, Kevin M Heinz, Peter C Krauter, Carlos F Gonzalez
Xylella fastidiosa subsp. fastidiosa (Xff) is the causal agent of Pierce's Disease (PD) of grapevines and is vectored by the glassy-winged sharpshooter (GWSS, Homalodisca vitripennis). Previously we have reported the development of a bacteriophage (phage) based biocontrol system for PD, but no information on insect transmission of phages has been reported. Here we communicate that laboratory reared GWSSs fed on cowpea plants (Vigna unguiculata subsp. unguiculata) harboring the virulent phage Paz were able to uptake of phage efficiently when the phage was present in high concentration, but were inefficient in transfer to plants.
{"title":"Transmission of phage by glassy-winged sharpshooters, a vector of <i>Xylella fastidiosa</i>.","authors":"Tushar Suvra Bhowmick, Mayukh Das, Kevin M Heinz, Peter C Krauter, Carlos F Gonzalez","doi":"10.1080/21597081.2016.1218411","DOIUrl":"10.1080/21597081.2016.1218411","url":null,"abstract":"<p><p><i>Xylella fastidiosa</i> subsp. <i>fastidiosa</i> (<i>Xff</i>) is the causal agent of Pierce's Disease (PD) of grapevines and is vectored by the glassy-winged sharpshooter (GWSS, <i>Homalodisca vitripennis</i>). Previously we have reported the development of a bacteriophage (phage) based biocontrol system for PD, but no information on insect transmission of phages has been reported. Here we communicate that laboratory reared GWSSs fed on cowpea plants (<i>Vigna unguiculata</i> subsp. <i>unguiculata</i>) harboring the virulent phage Paz were able to uptake of phage efficiently when the phage was present in high concentration, but were inefficient in transfer to plants.</p>","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85458338","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 : 2016-07-02DOI: 10.1080/21597081.2016.1220348
S. Abedon
ABSTRACT The concept of bacteriophage multiplicity of infection (MOI) – ratios of phages to bacteria – historically has been less easily applied than many phage workers would prefer or, perhaps, may be aware. Here, toward clarification of the concept, I discuss multiplicity of infection in terms of semantics, history, mathematics, pharmacology, and actual practice. For phage therapy and other biocontrol purposes it is desirable, especially, not to solely employ MOI to describe what phage quantities have been applied during dosing. Why? Bacterial densities can change between bacterial challenge and phage application, may not be easily determined immediately prior to phage dosing, and/or target bacterial populations may not be homogeneous with regard to phage access and thereby inconsistent in terms of what MOI individual bacteria experience. Toward experiment reproducibility and as practiced generally for antibacterial application, phage dosing instead should be described in terms of concentrations of formulations (phage titers) as well as volumes applied and, in many cases, absolute numbers of phages delivered. Such an approach typically will be far more desirable from a pharmacological perspective than solely indicating ratios of agents to bacteria. This essay was adapted, with permission, from an appendix of the 2011 monograph, Bacteriophages and Biofilms, Nova Science Publishers.
{"title":"Phage therapy dosing: The problem(s) with multiplicity of infection (MOI)","authors":"S. Abedon","doi":"10.1080/21597081.2016.1220348","DOIUrl":"https://doi.org/10.1080/21597081.2016.1220348","url":null,"abstract":"ABSTRACT The concept of bacteriophage multiplicity of infection (MOI) – ratios of phages to bacteria – historically has been less easily applied than many phage workers would prefer or, perhaps, may be aware. Here, toward clarification of the concept, I discuss multiplicity of infection in terms of semantics, history, mathematics, pharmacology, and actual practice. For phage therapy and other biocontrol purposes it is desirable, especially, not to solely employ MOI to describe what phage quantities have been applied during dosing. Why? Bacterial densities can change between bacterial challenge and phage application, may not be easily determined immediately prior to phage dosing, and/or target bacterial populations may not be homogeneous with regard to phage access and thereby inconsistent in terms of what MOI individual bacteria experience. Toward experiment reproducibility and as practiced generally for antibacterial application, phage dosing instead should be described in terms of concentrations of formulations (phage titers) as well as volumes applied and, in many cases, absolute numbers of phages delivered. Such an approach typically will be far more desirable from a pharmacological perspective than solely indicating ratios of agents to bacteria. This essay was adapted, with permission, from an appendix of the 2011 monograph, Bacteriophages and Biofilms, Nova Science Publishers.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81678234","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 : 2016-07-02DOI: 10.1080/21597081.2016.1220347
N. Soffer, T. Abuladze, Joelle E. Woolston, Manrong Li, L. F. Hanna, Serena Heyse, D. Charbonneau, A. Sulakvelidze
ABSTRACT Contamination of pet food with Salmonella is a serious public health concern, and several disease outbreaks have recently occurred due to human exposure to Salmonella tainted pet food. The problem is especially challenging for raw pet foods (which include raw meats, seafood, fruits, and vegetables). These foods are becoming increasingly popular because of their nutritional qualities, but they are also more difficult to maintain Salmonella-free because they lack heat-treatment. Among various methods examined to improve the safety of pet foods (including raw pet food), one intriguing approach is to use bacteriophages to specifically kill Salmonella serotypes. At least 2 phage preparations (SalmoFresh® and Salmonelex™) targeting Salmonella are already FDA cleared for commercial applications to improve the safety of human foods. However, similar preparations are not yet available for pet food applications. Here, we report the results of evaluating one such preparation (SalmoLyse®) in reducing Salmonella levels in various raw pet food ingredients (chicken, tuna, turkey, cantaloupe, and lettuce). Application of SalmoLyse® in low (ca. 2–4×106 PFU/g) and standard (ca. 9×106 PFU/g) concentrations significantly (P < 0.01) reduced (by 60–92%) Salmonella contamination in all raw foods examined compared to control treatments. When SalmoLyse®-treated (ca. 2×107 PFU/g) dry pet food was fed to cats and dogs, it did not trigger any deleterious side effects in the pets. Our data suggest that the bacteriophage cocktail lytic for Salmonella can significantly and safely reduce Salmonella contamination in various raw pet food ingredients.
{"title":"Bacteriophages safely reduce Salmonella contamination in pet food and raw pet food ingredients","authors":"N. Soffer, T. Abuladze, Joelle E. Woolston, Manrong Li, L. F. Hanna, Serena Heyse, D. Charbonneau, A. Sulakvelidze","doi":"10.1080/21597081.2016.1220347","DOIUrl":"https://doi.org/10.1080/21597081.2016.1220347","url":null,"abstract":"ABSTRACT Contamination of pet food with Salmonella is a serious public health concern, and several disease outbreaks have recently occurred due to human exposure to Salmonella tainted pet food. The problem is especially challenging for raw pet foods (which include raw meats, seafood, fruits, and vegetables). These foods are becoming increasingly popular because of their nutritional qualities, but they are also more difficult to maintain Salmonella-free because they lack heat-treatment. Among various methods examined to improve the safety of pet foods (including raw pet food), one intriguing approach is to use bacteriophages to specifically kill Salmonella serotypes. At least 2 phage preparations (SalmoFresh® and Salmonelex™) targeting Salmonella are already FDA cleared for commercial applications to improve the safety of human foods. However, similar preparations are not yet available for pet food applications. Here, we report the results of evaluating one such preparation (SalmoLyse®) in reducing Salmonella levels in various raw pet food ingredients (chicken, tuna, turkey, cantaloupe, and lettuce). Application of SalmoLyse® in low (ca. 2–4×106 PFU/g) and standard (ca. 9×106 PFU/g) concentrations significantly (P < 0.01) reduced (by 60–92%) Salmonella contamination in all raw foods examined compared to control treatments. When SalmoLyse®-treated (ca. 2×107 PFU/g) dry pet food was fed to cats and dogs, it did not trigger any deleterious side effects in the pets. Our data suggest that the bacteriophage cocktail lytic for Salmonella can significantly and safely reduce Salmonella contamination in various raw pet food ingredients.","PeriodicalId":8686,"journal":{"name":"Bacteriophage","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86736057","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 : 2016-07-02DOI: 10.1080/21597081.2016.1220349
Casey Stamereilers, L. Leblanc, Diane G. Yost, P. Amy, Philippos K. Tsourkas
ABSTRACT American Foulbrood Disease, caused by the bacterium Paenibacillus larvae, is one of the most destructive diseases of the honeybee, Apis mellifera. Our group recently published the sequences of 9 new phages with the ability to infect and lyse P. larvae. Here, we characterize the genomes of these P. larvae phages, compare them to each other and to other sequenced P. larvae phages, and putatively identify protein function. The phage genomes are 38–45 kb in size and contain 68–86 genes, most of which appear to be unique to P. larvae phages. We classify P. larvae phages into 2 main clusters and one singleton based on nucleotide sequence identity. Three of the new phages show sequence similarity to other sequenced P. larvae phages, while the remaining 6 do not. We identified functions for roughly half of the P. larvae phage proteins, including structural, assembly, host lysis, DNA replication/metabolism, regulatory, and host-related functions. Structural and assembly proteins are highly conserved among our phages and are located at the start of the genome. DNA replication/metabolism, regulatory, and host-related proteins are located in the middle and end of the genome, and are not conserved, with many of these genes found in some of our phages but not others. All nine phages code for a conserved N-acetylmuramoyl-L-alanine amidase. Comparative analysis showed the phages use the “cohesive ends with 3′ overhang” DNA packaging strategy. This work is the first in-depth study of P. larvae phage genomics, and serves as a marker for future work in this area.
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