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The genus Staphylococcus is a member of the family Micrococcaceae which includes three other general Micrococcus, Planococcus and Aerococcus. The four which have the same morphology and gram reaction may be distinguished from each other on the basis of arrangement, the utilization of glucose, the presence or abscence of cytochromes, oxygen requirements, motility and the G + C content of DNA. (Table I), The genus Staphylococcus includes three species; S. aureus, S. epidermidis and S. saprophyticus. These may be distinguished from each other on the basis of coagulase production, mannitol utilization, production of alpha toxin, presence of heat resistant endonucleases, requirement of biotin for growth, sensitivity to novobiocin and cell wall composition (Table II). In the early studies involving phages types and antibiotic susceptibilities, dilution methods (MIC) were used to determine susceptibility. With the adoption of the Kirby-Bauer technique, its wide clinical use, and the dynamic changes occurring in the staphylococci with respect to antibiotic susceptibility and phage patterns. Reexamination of these relationships becomes important and essential. Since no studies of this kind have ever been attempted on staphylococci from this community, it was decided to investigate the problem with respect to enzymatic activity, antibiogram and phage type and compare the findings with those from other geographic locations.

Prokaryotic genomes evolve via horizontal gene transfer (HGT), mutations, and rearrangements. HGT is a mechanism that plays a significant role in prokaryotic evolution and leads to biodiversity in nature. One of the important components of HGT is the genomic island (GI) which is a subsequence of the genome created by HGT. This research aims to identify the structures of the prokaryotic GIs that have a fundamental role in the adoption of prokaryotes and the impact of the species on the environment. Previous computational biology research has focused on developing tools that detect GIs in prokaryotic genomes, while there is little research investigating GI structure. This research introduces a novel idea that has not yet been addressed intensively, which is identifying additional structures of the GIs in prokaryotes. There are two main directions in this research used to study the prokaryotic GIs structure from each different perspective. In the first direction, the aim is to investigate GI patterns and the existence of biological connections across bacterial phyla in terms of GIs on a large scale. This direction mainly aims to pursue the novel idea of connecting GIs across prokaryotic and phage genomes via patterns of protein families across many species. A pattern is a sequence of protein families that is found to frequently occur in the genomes of a number of species. Here the large data set available from the IslandViewer4 database and protein families from the Pfam database have been combined. Furthermore, implementing a comprehensive strategy to identify patterns that makes use of HMMER, BLAST, and MUSCLE; also implement Python programs that link the analysis into a single pipeline. Research results demonstrate that related GIs often exist in multiple species that are not evolutionarily related and indeed may be from multiple bacterial phyla. Analysis of the discovered patterns led to the identification of biological connections among prokaryotes and phages through their GIs. A connection is an HGT relation represented as a pattern that exists in a phage and a number of prokaryotic species. These discovered connections suggest quite broad HGT connections across the bacterial kingdom and its associated phages. In addition, these connections provide the basis for additional analysis of the breadth of HGT and the identification of individual HGT events that span bacterial phyla. Moreover, these patterns can suggest the basis for discovering the specific patterns in pathogenic GIs that could play a crucial role in antibiotic resistance. The second direction aims to identify the structure of the GIs in terms of their location within the genome. Prokaryotic GIs have been analyzed according to the genome structure that they are located in, whether it be a circular or a linear genome. The analysis is performed to study the GIs' location in relation to the oriC, investigating the nature of the distances between the GIs, and determining the distribution of GIs in the genome. The analysis has been performed on all of the GIs in the data set. Moreover, the GIs in one genome from each species and the GIs of the most frequent species are in the data set, in order to avoid bias. Overall, the results showed that there are preferable sites for the GIs in the genome. In the linear genomes, they are usually located in the origin of replication area and terminus, and in the circular genomes they are located in the terminus. / Doctor of Philosophy / Prokaryotes are one of the most abundant species on earth that play an essential role in naturally shaping the planet and its life. This research aims to identify the structure of a component in these species that has a fundamental role in the adoption of prokaryotes and the impact of the species on the environment. This component is a part of the genome named the genomic island (GI). This dissertation aims to identify the structure of the GIs in two different ways that have not yet been addressed extensively. The first direction aims to discover patterns in the GIs and then use them to bring to light biological connections between prokaryotic and bacteriophages. In this direction, a comprehensive strategy has been utilized to identify patterns and connections. This strategy uses several tools such as BLAST, HMMER, and MUSCLE. Furthermore, Python programs that link the analysis into a single pipeline have been implemented. In the second direction, an investigation has been performed to understand the nature of the GIs' locations within the genome. This direction addresses three different analysis techniques to achieve its target. The three analyses are studying the GIs' location in relation to the origin of replication, investigating the nature of the distances between the GIs, and discovering the location distribution of GIs in the genome. The analysis is performed on linear genomes and circular genomes separately. In each group of GIs, the data set has been utilized to see the results from different perspectives. The overall analysis in both directions relived several findings. In the first direction, the discovered patterns merit deep investigation based on the possibility that they are related to diseases. In addition, in prokaryotic genomes, there are specific sites where the GIs can be frequently seen that need further search to understand the relation between the GIs' location and the content of the GI in terms of proteins.

Tesis por compendio / [ES] Salmonella es una de las principales causas de toxiinfecciones alimentarias en el mundo. En Europa, en el último año tuvo lugar un total de 94.203 casos de salmonelosis, de los cuales 8.730 fueron en España. La principal fuente de la infección son los productos de origen animal, principalmente los huevos y la carne de pollo. Los Programas Nacionales de Control de Salmonella, han logrado reducir la prevalencia de la bacteria a nivel de campo. Sin embargo, cada año siguen surgiendo nuevos casos de salmonelosis en la especie humana, y se sigue detectando la presencia de la bacteria en las explotaciones avícolas. Por ello, se continúan buscando nuevas alternativas en la lucha contra la bacteria, como puede ser el empleo de bacteriófagos. Los bacteriófagos o fagos son virus ubicuos en el ambiente que están ampliamente distribuidos en la naturaleza. Son microorganismos que atacan específicamente a bacterias, alterándolas hasta destruirlas. Estas características hacen de los fagos una herramienta muy prometedora para la eliminación de Salmonella en explotaciones avícolas como medida complementaria a la limpieza y desinfección, y como una herramienta más de control para incluir en las buenas prácticas de higiene a nivel de campo. En este contexto, en esta tesis doctoral hemos centrado nuestros estudios en conocer la diversidad fágica en las explotaciones avícolas y estudiar la aplicación de la terapia fágica para el control de Salmonella como medida complementaria a la limpieza y desinfección. Para ello, se realizaron tres experimentos durante el periodo de enero de 2017 y diciembre de 2019, en los que se aislaron y multiplicaron fagos de muestras procedentes de granjas avícolas. El objetivo del primer experimento fue evaluar la prevalencia de fagos frente a Salmonella en granjas comerciales de gallinas ponedoras y broilers. Los resultados de este estudio indican que las granjas avícolas podrían representar una importante fuente de fagos de Salmonella. Además, se ha observado una estrecha relación entre la prevalencia de fagos frente a Salmonella y la prevalencia de serotipos de Salmonella en las granjas avícolas, lo que sugiere que los fagos coexisten con su serotipo. su concentración y aplicarlos frente a las mismas granjas avícolas positivas a Salmonella. El objetivo del segundo experimento fue evaluar el efecto de los fagos contra Salmonella Infantis y Salmonella Enteritidis en las superficies de las granjas, y evaluar la aplicación del procedimiento de los fagos como desinfectante contra Salmonella en las condiciones de campo. Se observó una reducción de la concentración de S. Infantis y S. Enteritidis en las superficies de la nave en 4,55 log10 UFC/mL y 3,85 log10 UFC/mL, respectivamente. La mayor reducción para ambos serotipos se obtuvo el 5º día después de la primera aplicación. Estos resultados ponen de manifiesto que los fagos podrían ser una herramienta prometedora para utilizar en combinación con los procedimientos de limpieza y desinfección. Por último, el objetivo del tercer experimento fue evaluar la aplicación experimental de los autofagos para el control de S. Enteritidis en una granja de gallinas ponedoras contaminada de forma natural. Este estudio pone en evidencia que los autofagos se podrían emplear, no solo como una medida para reducir la excreción de Salmonella por parte de los animales infectados, sino como medida complementaria en la limpieza y desinfección de las instalaciones con una gran eficacia. Además, el hecho de que el autofago eliminara la Salmonella del medio ambiente, aún con los animales en el interior de la nave, podría evitar la re-contaminación horizontal entre animales infectados y no infectados. Los resultados más relevantes que se han obtenido de esta tesis doctoral es que el sector avícola dispone de una herramienta prometedora, económica y ecológica capaz de reducir significativamente la prevalencia de Salmonella cuando las medida / [EN] Millions of human salmonellosis cases are reported worldwide every year, and the disease results in thousands of deaths. In 2018, a total of 94,203 confirmed cases in humans were reported in Europe of which 8,730 were in Spain. The main source of infection is poultry products as eggs and chicken meat. National Salmonella Control Programmes have succeeded in reducing the prevalence of the bacteria at the field level. However, new cases of salmonellosis in humans continue to emerge every year and the presence of the bacterium continues to be detected in poultry farms. Therefore, new alternatives continue to be sought in the fight against the bacteria, such as the use of bacteriophages. Bacteriophages or phages are ubiquitous viruses in the environment and are widely distributed in nature. They are microorganisms that specifically attack bacteria, altering them until they are destroyed. These characteristics make phages a very promising tool for the elimination of Salmonella in poultry farms as a complementary tool for cleaning and disinfection, and as another control tool to be included in good hygiene practices at field level. Thus, in this doctoral thesis, we have focused our studies on determining the phage diversity in poultry farms and studying the application of phage therapy for the control of Salmonella as a complementary measure to cleaning and disinfection. To this end, three experiments were carried out during the period from January 2017 to December 2019, where phages were isolated, purified, and multiplied from different samples taken from poultry farms and their epidemiology was studied. The objective of the first experiment was to assess Salmonella-phage prevalence in commercial poultry farms in terms of the production livestock type: layers or broilers. The results of this study indicated that poultry farms could represent an important source of Salmonella phages. Moreover, we have shown a close relationship between Salmonella phage prevalence and Salmonella serovar prevalence in poultry farms, suggesting that phages co-exist within their serovar. The purpose of the second experiment was to assess the effect of phages against Salmonella Infantis and Salmonella Enteritidis on farm surfaces and evaluate phage application procedure as sanitiser against Salmonella in field conditions. Results showed S. Infantis and S. Enteritidis decreased by 4.55 log10 CFU/mL and 3.85 log10 CFU/mL, respectively; the maximum reduction in Salmonella was on the 5th day, after 108 PFU/mL and 103 PFU/mL phage application. These results highlight phages as a promising tool together with cleansing and disinfection. However, more studies are needed to demonstrate their efficacy as sanitisers in poultry farms. Finally, the aim of the third experiment was to assess the application of autophages for the control of S. Enteritidis in a naturally contaminated laying hen farm. This study shows that autophages could be used not only as a measure to reduce the excretion of Salmonella by infected animals but also as a complementary measure in the cleaning and disinfection of the facilities. In addition, the fact that autophages eliminated the Salmonella from the environment, even with the animals inside the facility, could avoid horizontal transmission of Salmonella among infected and non-infected animals. The most relevant results obtained from this doctoral thesis are that the poultry sector has a promising, economic and ecological tool, as phage therapy, able to significantly reduce the prevalence of Salmonella when current measures cannot eliminate it from poultry farms. / [CA] Salmonella és una de les principals causes de toxiinfeccions alimentàries en el món. En A Europa, en l'últim any es van reportar 94.203 casos, dels quals 8.730 es van produir a Espanya. La principal font d'infecció són els productes d'origen animal, principalment els ous i la carn de pollastre. Els Programes Nacionals de Control de Salmonella han aconseguit reduir la prevalença a nivell de camp. No obstant, cada any continuen sorgint nous casos de salmonel·losi, i es continua detectant la presència de la bacteria en algunes explotacions avícoles. Per això, es continua buscant noves alternatives en la lluita contra la bacteria, com pot ser l'ocupació d'additius en el pinso, un bon maneig a nivell de camp o l'ús de bacteriòfags. Els bacteriòfags o fags són virus ubics en l'ambient i es troben àmpliament distribuïts en la naturalesa. Són microorganismes que ataquen específicament a les bacteries, alterant-les fins a destruir-les. Estes característiques fan dels bacteriòfags una ferramenta molt prometedora per a l'eliminació de Salmonella en explotacions avícoles com a mesura complementària a la neteja i desinfecció i com una ferramenta més de control per a incloure en les bones pràctiques d'higiene. En este context, en esta tesi doctoral hem centrat els nostres estudis a conèixer la diversitat fàgica en les explotacions avícoles i estudiar l'aplicació de la teràpia fágica per al control de Salmonella com a mesura complementària a la neteja i desinfecció. Per a això, es van realitzar tres experiments durant el període de gener de 2017 i desembre de 2019, en els que es van aïllar y multiplicar bacteriòfags de diferents mostres procedents de granges avícoles. L'objectiu del primer experiment va ser avaluar la prevalença de bacteriòfags enfront de Salmonella en granges comercials de gallines ponedores i pollastres. Els resultants de este estudi indiquen que les granges avícoles podrien representar una important font enfront de bacteriòfags de Salmonella. A més, s'ha observat una estreta relació entre la prevalença de bacteriòfags enfront de Salmonella i la prevalença de serotips de Salmonella en les granges avícoles, la qual cosa suggereix que els bacteriòfags coexisteixen amb el seu serotip. L'objectiu del segon experiment va ser avaluar l'efecte dels bacteriòfags contra Salmonella Infantis i Salmonella Enteritidis en les superfícies de les granges, i avaluar l'aplicació del procediment dels bacteriòfags com a desinfectant contra Salmonella en les condicions de camp. La concentració de Salmonella Infantis i Salmonella Enteritidis va disminuir 4,55 log10 UFC/mL i 3,85 log10 UFC/mL, respectivament, després de dos aplicacions consecutives de bacteriòfags. La major reducció de S. Infantis i S. Enteritidis es va obtindre el 5º dia després de la primera aplicació. Estos resultats manifesten que els bacteriòfags són una ferramenta prometedora per a utilitzar en combinació amb els procediments de neteja i desinfecció. Finalment, l'objectiu del tercer experiment va ser avaluar l'aplicació experimental dels autòfags per al control de S. Enteritidis en una granja de gallines ponedores. Este estudi posa en evidència que els autofagos es podrien emprar com a mesura complementària en la neteja i desinfecció de les instal·lacions amb una gran eficàcia i per a reduir els recomptes de Salmonella en animals infectats. A més, el fet de que l'autòfag eliminarà la Salmonella del medi ambient, encara amb els animals en l'interior de la nau, podria evitar la recontaminació horitzontal entre animals infectats i no infectats. Els resultats més rellevants que s'han obtingut d'esta tesi doctoral és que el sector avícola disposa d'una ferramenta prometedora, econòmica i ecològica capaç de reduir significativament la prevalença de Salmonella quan les mesures actuals no són capaços d'eliminar-la de les granges avícoles. / Agradecer al Centro de Calidad Avícola y Alimentación Animal de la Comunidad Valenciana (CECAV) por su apoyo para realizar este proyecto. En especial, al comité técnico de Asociación Avícola Valenciana (ASAV) por la iniciativa de este proyecto y a los miembros de la Junta Directiva de CECAV por la financiación. / Sevilla Navarro, S. (2020). Selection and assessment of bacteriophages against salmonella spp. in the poultry industry [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/149561 / Compendio

With a decline in antibiotic effectiveness, there is a renewed interest in using bacterial-specific viruses (bacteriophages or phages) to reduce bacterial loads, alone or with antibiotics. Most phages are therapeutically unsuitable because they are “temperate” and can integrate into the host genome, protecting the host from subsequent phage infections. However, dormant phages can be awakened by stressors such as antibiotics. Here we investigated whether antibiotics can uniquely interact with temperate phages to bias the phage away from dormancy. Model E. coli temperate phage and ciprofloxacin, a DNA-damaging antibiotic, exhibit a potent synergy, resulting in bacterial eradication at sublethal antibiotic concentrations, despite poor killing by the phage alone. Mechanistically, this synergy depletes survivors by awakening dormant phages. To broaden our findings, screening in the multi-drug-resistant pathogen P. aeruginosa, we identified phages that can synergize with four antibiotic classes, despite their widely differing targets - however, these are highly phage, antibiotic, and host-specific. Interestingly, ciprofloxacin also synergized with multiple phages, even in a ciprofloxacin-resistant clinical strain, functionally re-sensitizing the bacterium to the antibiotic. While some of these interactions operated through a mechanism independent of the temperate nature of the phages, ciprofloxacin and piperacillin, a cell wall synthesis inhibitor, specifically reduced the frequency of phage dormancy events. Finally, in a Caenorhabditis elegans infection model, temperate phage-ciprofloxacin pairing increased the lifespan of drug-resistant P. aeruginosa infected worms compared to the uninfected control. Similar rescue was also observed for the phage-carrying strain treated with the antibiotic, supporting that the phage even in its dormant form can enhance antibiotic effectiveness. Overall, we show that temperate phages uniquely synergize with antibiotics at the level of biasing the phage away from dormancy. This is generalizable across phages, antibiotics, and hosts, and shows efficacy in vivo, thereby drastically expanding their therapeutic potential. / Thesis / Doctor of Philosophy (PhD) / Bacteriophages (phages) are bacterial viruses that present a promising solution to the antibiotic resistance crisis. They can kill bacteria even when antibiotics fail, alone or in combination with them. Most work to date focuses on phages that immediately lyse the bacteria. However, phages that can go dormant within the host are far more abundant but largely ignored in therapy. Once integrated, these can awaken to switch into lytic replication by external triggers that stress the bacterial host, including antibiotics. Supported by this idea, in this thesis I show that these kinds of phages can synergistically interact with antibiotics by biasing the phage away from dormancy. This phenomenon is generalizable across host, phages, and antibiotics and shows effectiveness in an animal model.

Bacteriophages, or simply "phages," are the most abundant biological entities on the planet and are thought to be the largest untapped reservoir of available genetic information. They are also important contributors to both soil health and nutrient recycling and have significantly influenced our current understanding of molecular biology. Bacteria in the genus Streptomyces are also known to be important contributors to soil health, as well as producing a number of useful antibiotics. The genetic diversity of large (> 30) groups of other actinobacteriophages, i.e. phages infecting a few close relatives of the Streptomycetes, has been explored, but this is the first formal effort for Streptomyces-infecting phages. Described here are a group of 45 phages, isolated from soil using a single Streptomycete host, Streptomyces griseus ATCC 10137. All 45 phages are tailed phages with double-stranded DNA. Siphoviruses predominate, six of the phages are podoviruses, and no myoviruses were observed. Notably present are seven phages with prolate icosahedral capsids. Genome lengths and genome termini vary considerably, and the distributions of each are in line with findings among other groups of studied actinobacteriophages. Interestingly, the average G+C among the 45 phages is around 11% lower than that of the isolation host, a larger disparity than reported for other groups of actinobacteriophages. Eighteen of the phages carry between 17 and 45 tRNAs and 12 of those carry a single tmRNA. Forty-three phages were grouped into seven clusters and two subclusters based on dot plot analysis, average nucleotide identities, and gene content similarities. Two phages were not clustered with other phages in this dataset. A total of 5250 predicted genes were sorted into 1300 gene "phamilies," with about 8% of the total phamilies having only a single member. Analysis of gene content among the 45 phages indicates first that most clusters presented here appear to be relatively isolated from one another, with phages in any one cluster generally sharing < 10% of their genes with phages in other clusters described here. Secondly, most of the phages here are more than twice as likely to share genes with phages isolated on bacteria outside of the genus Streptomyces than they are other phages isolated using a Streptomycete as host. These observations suggest that (1) the phage clusters here have a distinct extended host range, (2) those host ranges share overlap, and (3) Streptomyces griseus is likely not the preferred natural host for all phages described.

Antibodies are one of the most useful molecules with affinity of binding and specificity for in vitro and in vivo diagnosis, or for immunotherapy of human diseases. In recent years, phage-displayed antibody library has been widely adopted to select tailor-made antibodies in a fast, high-throughput mode, as an alternative of traditional hybridoma technology. Although phage display has been introduced for about 20 years, the applications and development of this technology still have a rich space to be explored. / Attempts are made in the present study to extend three applications of the phage displayed antibody library in antibody discovery and engineering. Firstly, a CDR3-randomized phage-displayed scFv library was constructed from genomic DNA of mouse. Following biopanning, anti-peptide of mas oncoprotein scFvs were isolated and identified. These results illustrate the potential use of the genomic phage-displayed library for anti-peptide antibodies selection. Secondly, we described the isolation of anti-idiotypic scFvs against a chimeric anti-CD22 mAb from an immunized phage-displayed scFv library. The isolated anti-Id scFvs were able to capture the immune response of chimeric anti-CD22 mAb with high specificity. This reagent will enhance our understanding of the therapeutic mechanism of anti-CD22 mAb in non-Hodgkin's lymphoma treatment, and may be applied to probe the pharmacokinetics, tissue distribution, and modulation of anti-CD22 mAb in vivo. / In conclusion, we have attempted various approaches to identify specific anti-peptide scFvs, anti-idiotypic scFvs and passive anti-tumor scFvs. These results extend the applications of phage display technology in antibody discovery and engineering. / Our approach enables us to isolate selective and sensitive anti-idiotypic antibodies and could be exploited for other antibodies with clinical and biological applications. Thirdly, we profile a strategy to select and identify markers on tumor cell surface using phage-displayed antibodies from mice bearing xenograft tumor. Our data imply that passive antibodies in cancer patients may be obtained from the immune repertoire of cancer patients. Besides, we found a cell surface antigen was up-regulated more than 3-fold in mas-expressing cells. We further use the targeting antibody to construct a tumor endoprotease-activated immunotoxin. / Zhao, Qi. / Adviser: Wing-Tai Cheung. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3499. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 227-250). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Mannheimia haemolytica is the principal bacterial agent associated with bovine respiratory disease (BRD). It has a significant economic impact on the beef feedlot industry. The current methods for BRD prevention and treatment have various problems and limitations, especially with reports of increased antimicrobial resistance in M. haemolytica. Bacteriophage therapy presents a novel method to mitigate M. haemolytica. This study aimed to isolate strictly lytic M. haemolytica-specific bacteriophages from bovine nasopharyngeal swabs and feedlot trough water. This was accompanied by an extensive characterization of temperate bacteriophages induced from representative strains of a M. haemolytica collection. Phage morphology, host specificity, genomic diversity, and comparative genomics were determined. Even though temperate bacteriophages are not ideal candidates for phage therapy, they can be engineered or modified to serve this function. Genome sequences of selected temperate bacteriophages also provide a foundation for future studies on the biology of these microorganisms. / viii, 107 leaves : ill. ; 29 cm

Submitted in partial fulfillment of the academic requirements for the degree of Master of Technology: Biotechnology, 2009. / Production of numerous biotechnologically-important products such as threonine is based on cultivation of bacterial cultures. Infection of these bacterial cultures by bacteriophages has a detrimental effect in the production of these bioproducts. Despite this, most people controlling these bioprocesses do not recognize the early signs of bacteriophage infection. SA Bioproducts (Ply) Ltd was no exception and has suffered tremendous loss of production time after bacteriophages infected threonine producing E. coli strain B. This study was aimed at developing assays to control and prevent bacteriophage infection at this company. These included determining the source of phages by monitoring the process plant environment, optimising the detection and enumeration methods so as to monitor the levels of bacteriophages in the environment, identification of bacteriophages in order to determine the number of bacteriophages capable of infection threonine producing E. coli strain B, treatment and of phages, and possible prevention of phage infection. Adam's DAL method was very efficient at detecting phages in the samples collected at various areas (sumps, odour scrubber, process water, and soil) around the plant for 16 weeks. High levels of phages were found in the sumps and this was identified as the source of infection. Samples collected were grouped together according to their source. The samples were enriched and purified in order to characterise them. The prevalent phage in all samples was identified as a T1-like phage. Bacterial strains that grew on the plate in the presence of phages were assumed to be resistant to phages or contained lysogenic phages which would explain the new lytic cycles that were observed whenever these resistant strains were used for production. UV light, green v indicator plates, and a mutagen (Mitomycin C) were used to detect Iysogens. Mitomycin C at 1 IJg/ml was found to be most effective in detecting lysogenic phages. This was shown by new plaque forming units that were visible on the DAL plates. Temperature (heat), chemicals, and inhibitors (vitamins) were investigated as strategies for prevention and treatment of bacteriophage infection. Bacteriophage samples were exposed to 70, 80, 100, and 120°C. At these temperatures pfu counts in the samples were reduced significantly. At 120°C there was a complete inactivation of bacteriophages within 30 minutes. Chemicals investigated such as sodium hydroxide and Albrom 100T were capable of complete deactivation of bacteriophages at a very low concentration (0.1%). Therefore, these chemicals can be used to clean the plant area and sumps. Vitamins C, K and E solutions were investigated to determine their inhibitory effect on bacteriophages. Vitamin C, K and E reduced pfu counts by 3, 2, and 4 logs, respectively. Therefore vitamin C and E solutions were mixed and to determine if mixing them would enhance their inactivation capabilities. This resulted in a reduction greater than 9 logs of phage in the sample (from 7.7 x 109 to 3 pfu/ml). The host bacterium was also exposed to this mixture to determine effect of the vitamin mixture on its growth. It was found that there was no effect exerted by this mixture on the host bacteria. This proved to be an ideal mixture for combating phages during fermentation. However, vitamin E is not cost effective for co-feeding in 200 m' fermenters, and therefore vitamin C solution was a cost-effective alternative. It was concluded that bacteriophage contaminated bioprocessing plant should be properly cleaned using a combination of heat and chemicals. Bacteriophage infection should be prevented by employing inhibitors.