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Prostate cancer is the most common cancer among Swedish men, but the aetiology of this disease is largely unknown. There is evidence for a linkage between chronic inflammation and prostate cancer. The mechanisms causing prostate inflammation and how this could promote tumour development and progression are however largely unknown. Chronic inflammatory infiltrates are common findings in prostate tissue samples and infection is proposed to be one possible cause for this inflammation. Inflammatory cells release free radicals, cytokines, and growth factors that facilitate increased cell proliferation, DNA damage, mutations, and angiogenesis. However, the present literature on the presence of microbes in prostate tissue and their possible linkage to inflammation and cancer development is limited. Therefore, the aim of this thesis was to investigate if microorganisms are present in prostate tissue and to evaluate their role in inducing prostatitis and prostate epithelial neoplasia. The presence of microorganisms (virus, bacteria and fungi) was studied in clinical prostate tissue samples to evaluate whether or not the occurrences of microorganisms were different in patients that later developed cancer compared with matched controls that did not. Viruses, bacteria and fungi were found in prostate tissues. Out of eight different viruses investigated, EBV and JC virus were detected, but there were no differences in occurrence in the case group compared to the control group. The fungus Candida albicans was present in a very small proportion of the prostate tissue samples. The predominant bacterium was Propionibacterium acnes and the second most prevalent was Escherichia coli. The presence of Propionibacterium acnes was associated with inflammation and subsequent prostate cancer development. Propionibacterium acnes was further evaluated for its capacity to induce an inflammatory response both in vitro and in vivo. Live Propionibacterium acnes induced a strong immune reaction in prostate epithelial cells in vitro with up-regulation of inflammatory genes and secretion of pro-inflammatory cytokines. Infection with Propionibacterium acnes in rat prostate resulted in a lobe specific inflammation with the most intense inflammation in the dorso-lateral prostate, lasting up to 3 months post-inoculation. Propionibacterium acnes inflammation was also associated with altered epithelial cell morphology, signs of DNA damage and increased cell proliferation. Taken together, this thesis shows that different viruses and bacteria can be found in prostate tissue. Propionibacterium acnes, the most abundant among the bacteria detected and more prevalent in the cancer than in the control group, exhibits strong prostatitis promoting properties both in vitro and in vivo. In addition, Propionibacterium acnes can induce some of the epithelial changes known to occur during prostate neoplasia formation. This thesis therefore suggests that Propionibacterium acnes induced chronic prostatitis could promote prostate cancer development. Further studies are needed to elucidate the molecular interplay linking Propionibacterium acnes induced inflammation and the formation of a pre-neoplastic state that could evolve into prostate cancer.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xvii, 143 p.; also includes graphics. Includes bibliographical references (p. 106-111). Available online via OhioLINK's ETD Center

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No / Background Propionibacterium acnes and P. granulosum are widely regarded as the aetiological agents of inflammatory acne. Their proliferation and metabolism are controlled using lengthy courses of oral and/or topical antibiotics. Despite numerous reports of skin colonization by antibiotic-resistant propionibacteria among acne patients, accurate prevalence data are available only for the U.K. Objectives To determine the prevalence of skin colonization by antibiotic-resistant propionibacteria among acne patients and their contacts from six European centres. Methods Skin swabs were collected from 664 acne patients attending centres in the U.K., Spain, Italy, Greece, Sweden and Hungary. Phenotypes of antibiotic-resistant propionibacteria were determined by measuring the minimum inhibitory concentrations (MIC) of a panel of tetracycline and macrolide, lincosamide and streptogramin B (MLS) antibiotics. Resistance determinants were characterized by polymerase chain reaction (PCR) using primers specific for rRNA genes and erm(X), followed by nucleotide sequencing of the amplified DNA. Results Viable propionibacteria were recovered from 622 patients. A total of 515 representative antibiotic-resistant isolates and 71 susceptible isolates to act as control strains were characterized phenotypically. The prevalence of carriage of isolates resistant to at least one antibiotic was lowest in Hungary (51%) and highest in Spain (94%). Combined resistance to clindamycin and erythromycin was much more common (highest prevalence 91% in Spain) than resistance to the tetracyclines (highest prevalence 26·4% in the U.K.). No isolates resistant to tetracycline were detected in Italy, or in Hungary. Overall, there were strong correlations with prescribing patterns. Prevalence of resistant propionibacteria on the skin of untreated contacts of the patients varied from 41% in Hungary to 86% in Spain. Of the dermatologists, 25 of 39 were colonized with resistant propionibacteria, including all those who specialized in treating acne. None of 27 physicians working in other outpatient departments harboured resistant propionibacteria. Conclusions The widespread use of topical formulations of erythromycin and clindamycin to treat acne has resulted in significant dissemination of cross-resistant strains of propionibacteria. Resistance rates to the orally administered tetracycline group of antibiotics were low, except in Sweden and the U.K. Resistant genotypes originally identified in the U.K. are distributed widely throughout Europe. Antibiotic-resistant propionibacteria should be considered transmissible between acne-prone individuals, and dermatologists should use stricter cross-infection control measures when assessing acne in the clinic. Background Propionibacterium acnes and P. granulosum are widely regarded as the aetiological agents of inflammatory acne. Their proliferation and metabolism are controlled using lengthy courses of oral and/or topical antibiotics. Despite numerous reports of skin colonization by antibiotic-resistant propionibacteria among acne patients, accurate prevalence data are available only for the U.K. Objectives To determine the prevalence of skin colonization by antibiotic-resistant propionibacteria among acne patients and their contacts from six European centres. Methods Skin swabs were collected from 664 acne patients attending centres in the U.K., Spain, Italy, Greece, Sweden and Hungary. Phenotypes of antibiotic-resistant propionibacteria were determined by measuring the minimum inhibitory concentrations (MIC) of a panel of tetracycline and macrolide, lincosamide and streptogramin B (MLS) antibiotics. Resistance determinants were characterized by polymerase chain reaction (PCR) using primers specific for rRNA genes and erm(X), followed by nucleotide sequencing of the amplified DNA. Results Viable propionibacteria were recovered from 622 patients. A total of 515 representative antibiotic-resistant isolates and 71 susceptible isolates to act as control strains were characterized phenotypically. The prevalence of carriage of isolates resistant to at least one antibiotic was lowest in Hungary (51%) and highest in Spain (94%). Combined resistance to clindamycin and erythromycin was much more common (highest prevalence 91% in Spain) than resistance to the tetracyclines (highest prevalence 26·4% in the U.K.). No isolates resistant to tetracycline were detected in Italy, or in Hungary. Overall, there were strong correlations with prescribing patterns. Prevalence of resistant propionibacteria on the skin of untreated contacts of the patients varied from 41% in Hungary to 86% in Spain. Of the dermatologists, 25 of 39 were colonized with resistant propionibacteria, including all those who specialized in treating acne. None of 27 physicians working in other outpatient departments harboured resistant propionibacteria. Conclusions The widespread use of topical formulations of erythromycin and clindamycin to treat acne has resulted in significant dissemination of cross-resistant strains of propionibacteria. Resistance rates to the orally administered tetracycline group of antibiotics were low, except in Sweden and the U.K. Resistant genotypes originally identified in the U.K. are distributed widely throughout Europe. Antibiotic-resistant propionibacteria should be considered transmissible between acne-prone individuals, and dermatologists should use stricter cross-infection control measures when assessing acne in the clinic. Background Propionibacterium acnes and P. granulosum are widely regarded as the aetiological agents of inflammatory acne. Their proliferation and metabolism are controlled using lengthy courses of oral and/or topical antibiotics. Despite numerous reports of skin colonization by antibiotic-resistant propionibacteria among acne patients, accurate prevalence data are available only for the U.K. Objectives To determine the prevalence of skin colonization by antibiotic-resistant propionibacteria among acne patients and their contacts from six European centres. Methods Skin swabs were collected from 664 acne patients attending centres in the U.K., Spain, Italy, Greece, Sweden and Hungary. Phenotypes of antibiotic-resistant propionibacteria were determined by measuring the minimum inhibitory concentrations (MIC) of a panel of tetracycline and macrolide, lincosamide and streptogramin B (MLS) antibiotics. Resistance determinants were characterized by polymerase chain reaction (PCR) using primers specific for rRNA genes and erm(X), followed by nucleotide sequencing of the amplified DNA. Results Viable propionibacteria were recovered from 622 patients. A total of 515 representative antibiotic-resistant isolates and 71 susceptible isolates to act as control strains were characterized phenotypically. The prevalence of carriage of isolates resistant to at least one antibiotic was lowest in Hungary (51%) and highest in Spain (94%). Combined resistance to clindamycin and erythromycin was much more common (highest prevalence 91% in Spain) than resistance to the tetracyclines (highest prevalence 26·4% in the U.K.). No isolates resistant to tetracycline were detected in Italy, or in Hungary. Overall, there were strong correlations with prescribing patterns. Prevalence of resistant propionibacteria on the skin of untreated contacts of the patients varied from 41% in Hungary to 86% in Spain. Of the dermatologists, 25 of 39 were colonized with resistant propionibacteria, including all those who specialized in treating acne. None of 27 physicians working in other outpatient departments harboured resistant propionibacteria. Conclusions The widespread use of topical formulations of erythromycin and clindamycin to treat acne has resulted in significant dissemination of cross-resistant strains of propionibacteria. Resistance rates to the orally administered tetracycline group of antibiotics were low, except in Sweden and the U.K. Resistant genotypes originally identified in the U.K. are distributed widely throughout Europe. Antibiotic-resistant propionibacteria should be considered transmissible between acne-prone individuals, and dermatologists should use stricter cross-infection control measures when assessing acne in the clinic.

Orientador: Gonçalo Amarante Guimarães Pereira / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-25T04:53:49Z (GMT). No. of bitstreams: 1 Negri_VictorAugusti_M.pdf: 12106388 bytes, checksum: d15b4a2052af5e412ac086681ebf3a4b (MD5) Previous issue date: 2014 / Resumo: Propionibacterium acidipropionici é uma bactéria gram-positiva que apresenta a capacidade de produzir ácido propiônico em sua via fermentativa, composto de grande importância na indústria petroquímica e alimentícia. Tendo-se em vista que esse ácido é hoje obtido através de derivados do petróleo, P. acidipropionici vem sendo apontada como uma potencial plataforma industrial na produção de ácido propiônico. Uma das características que enfatizam a sua utilização está a sua capacidade em fixar CO2 e direcioná-lo para a produção de ácido propiônico. Entretanto, pouco se sabe sobre esse fenômeno em propionibactérias. O presente trabalho teve como objetivo caracterizar e estudar o metabolismo de assimilação de CO2 em P. acidipropionici, visando avaliar a relevância do mesmo na fermentação desta bactéria. Através da análise do genoma e resultados prévios de expressão global foram identificados potenciais genes envolvidos tanto na assimilação de CO2 quanto na produção de ácido propiônico, destacando-se a enzima piruvato carboxilase como uma importante candidata envolvida na fixação de CO2. Dados de expressão dessa enzima indicaram que a mesma tem sua expressão aumentada quando a bactéria é cultivada em glicerol como fonte de carbono, condição em que há uma maior produção de ácido propiônico. Outros genes que se destacaram foram os genes do metabolismo de biotina, cofator importante em enzimas fixadoras de dióxido de carbono. Foi descrito que os genes envolvidos na sua síntese estão ausentes em seu genoma e que os genes envolvidos em sua assimilação se mostraram diferencialmente expressos ao fim das fermentações em glicerol e glicose, indicando uma possível carência metabólica dessa vitamina. Adicionalmente, foi reportado que a assimilação de CO2 pode ocorrer em diferentes fontes de carbono, podendo apresentar até 25% de ácido propiônico e até 32% do ácido succínico, contendo pelo menos um carbono proveniente do CO2. Tais dados revelaram que a assimilação de CO2 é provavelmente um fenômeno recorrente e relevante em P. acidipropionici, o que reforça essa bactéria como uma promissora plataforma industrial. Por fim, experimentos realizados em biorreator indicaram que ambientes com alta disponibilidade de CO2 podem levar a um aumento expressivo da produção de ácido succínico, intermediário da via do ácido propiônico e também um importante produto de interesse da indústria química / Abstract: Propionibacterium acidipropionici is a gram-positive bacterium that has the ability to produce propionic acid through its fermentative pathway, a highly important compound in petrochemical and food industry. In view that nowadays this acid is obtained through petroleum derivatives, P. acidipropionici is being appointed as an important candidate as an industrial platform in propionic acid production. One of the characteristics that emphasize its use is the ability to fix CO2 and direct the assimilated carbon to the production of propionic acid. Little is known about this phenomenon in propionibacteria, however it¿s occurrence is described when the bacterium is cultivated in glycerol as its only carbon source. The present work had as objective to characterize and study the CO2 assimilation mechanism in P. acidipropionici, aiming to evaluate how relevant this mechanism is in its fermentative metabolism. Through genome analysis, genes and pathways potentially involved in this process were identified. The analysis highlights the enzyme pyruvate carboxylase, a propionic acid cycle¿s acting enzyme and little distributed in Propionibacteria, and the genes involved in biotin¿s metabolism, a vitamin that acts as an important cofactor in CO2 fixation reactions in bacteria. The biotin production pathway is not complete in P. acidipropionici, being observable in this project that in fact there is a deficiency in its growth in the absence of the same. Seeking trancriptional clues of the phenomenon and having glycerol as carbon source, a global gene expression analysis of the fermentation of P. acidipropionici was performed in glycerol, glucose and sugarcane juice in different points of bacterial growth (RNASeq). Interestingly, the most differentially expressed enzyme of the fermentative pathway in glycerol is the enzyme pyruvate carboxylase. The biotin related pathways are also differentially expressed at the final stages of the bacterium¿s fermentation, what can be related to a requirement of this vitamin at these stages. The supplementation of this vitamin was performed at the three studied carbon sources. However, no difference in growth or acids production was found. Aiming to explore in which situations the CO2 fixation happens, fermentations with six different carbon sources supplemented with carbon-13 containing sodium bicarbonate were performed. It was evaluated from this experiment that the CO2 assimilation occurs in all studied carbon sources, and that about 1/4 of the propionic acid total has a carbon that comes from the diluted bicarbonate. The generated data reveals that the phenomenon is relevant in P. acidipropionici. Lastly, the effect of sodium bicarbonate supplementation in P. acidipropionici fermentations having glycerol as carbon source was studied. As a result, an expressive increase in the production of succinic acid was observed, another fermentation final product in propionibacteria. Such phenomenon, therefore, could also be more explored for the production of this second acid, equally important in the industrial point of view / Mestrado / Genetica de Microorganismos / Mestre em Genética e Biologia Molecular

Orientador: Gustavo Paim Valença / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química / Made available in DSpace on 2018-08-26T07:00:33Z (GMT). No. of bitstreams: 1 Duarte_JulianaCanto_D.pdf: 4804028 bytes, checksum: 8a14cd7e6bdf26f6d7000302437af726 (MD5) Previous issue date: 2014 / Resumo: Foram realizadas fermentações em batelada do sorbitol, sacarose, glicerol e glicose por Propionibacterium acidipropionici livre em biorreatores. As fermentações do sorbitol forneceram a maior concentração final de ácido propiônico (39,5±5,2 g L-1) e as fermentações da glicose forneceram a menor concentração final de ácido propiônico (23,9±2,1 g L-1). Apenas as fermentações do glicerol produziram n-propanol e sua concentração final foi de 1,7±0,1 g L-1, além disso, o ácido acético não foi produzido nas fermentações do glicerol. As fermentações da sacarose forneceram a maior concentração final de ácido acético (10,9±0,0 g L-1). O maior valor de produtividade do ácido propiônico foi obtido nas fermentações do sorbitol (0,60 g L-1 h-1). Fermentações do sorbitol e da sacarose em batelada utilizando células de P. acidipropionici livres e imobilizadas em montmorilonita K10 foram realizadas em três ciclos sequenciais com reciclo celular. As concentrações finais de ácido propiônico para as fermentações do sorbitol com células livres foram 39,5±5,2; 35,8±1,4 e 34,4±1,9 g L-1 e para células imobilizadas foram 33,1±0,7; 37,2±0,6 e 36,6±0,4 g L-1, para o primeiro, segundo e terceiro ciclos sequenciais, respectivamente. O maior valor de produtividade e de rendimento do ácido propiônico nas fermentações do sorbitol foi obtido para o primeiro ciclo com células livres: 0,60 g L-1 h-1 e 0,613 g g-1, respectivamente. As concentrações finais de ácido propiônico para as fermentações da sacarose com células livres foram 33,4±0,3; 31,3±0,9 e 31,1±0,1 g L-1 e para células imobilizadas foram 26,9±0,6; 29,1±0,3 e 29,5±0,8 g L-1 para o primeiro, segundo e terceiro ciclos sequenciais, respectivamente. A produtividade e o rendimento do ácido propiônico foram maiores no primeiro ciclo para células livres: 0,48 g L-1 h-1 e 0,409 g g-1, respectivamente. Foram realizadas co-fermentações de glicose:glicerol em duas razões mássicas (1:1 e 2:1) em batelada utilizando P. acidipropionici livre e imobilizada em montmorilonita K10. Apenas nas co-fermentações foi observada a produção do ácido lático e trealose além dos ácidos acético, succínico e propiônico. A maior concentração final de ácido propiônico foi obtida para as co-fermentações glicose:glicerol de razão mássica 2:1 com células de P. acidipropionici livres (31,4±0,3 g L-1) e a menor concentração final foi obtida nas co-fermentações de razão mássica 1:1 para células imobilizadas (23,9±0,8 g L-1). O ácido acético foi produzido apenas nas co-fermentações de razão mássica 2:1 para células livres (0,3±0,4 g L-1) e imobilizadas (1,1±0,2 g L-1). A maior concentração final de ácido lático foi obtida nas co-fermentações de razão mássica 1:1 para células livres (10,5±0,3 g L-1) e a menor concentração final foi obtida nas co-fermentações de razão mássica 2:1 para células livres (0,9±0,6 g L-1). A maior concentração final de trealose foi obtida nas co-fermentações de razão mássica 2:1 para células imobilizadas (12,1±0,1 g L-1) e a menor concentração final foi obtidas nas co-fermentações de razão mássica 2:1 para células livres (6,7±1,0 g L-1). O maior valor de produtividade e de rendimento do ácido propiônico foram obtidos nas co-fermentações de razão mássica 2:1 para células livres: 0,45 g L-1 h-1 e 0,412 g g-1, respectivamente / Abstract: Batch fermentations of sorbitol, sucrose, glycerol and glucose by free cells of Propionibacterium acidipropionici were conducted in bioreactors. Sorbitol fermentations yield the major final propionic acid concentration (39.5±5.2 g L-1) while glucose fermentations yield the minor result (23.9±2.1 g L-1). Only glycerol fermentations yield n-propanol (1.7±0.1 g L-1), furthermore, acetic acid was not generated in glycerol fermentations. In the other hand, sucrose fermentations yield great acetic acid final concentration (10.9±0.0 g L-1). The major propionic acid productivity was got in sorbitol fermentations (0.60 g L-1 h-1). Sorbitol and sucrose batch fermentations by free and immobilized cells of P. acidipropionici in montmorillonite K10 were carried out in three sequential cycles with cell reuse. The final propionic acid concentrations to sorbitol with free cells were 39.5±5.2; 35.8±1.4 e 34.4±1.9 g L-1 and with immobilized cells were 33.1±0.7; 37.2±0.6 e 36.6±0.4 g L-1, to the first, second and third sequential cycles, respectively. The major propionic acid productivity was got in the first cycle with free cells to sorbitol fermentations (0.60 g L-1 h-1). The major propionic acid yield was 0.613 g g-1 in the first cycle to free cells. The final propionic acid concentrations to sucrose fermentations with free cells were 33.4±0.3; 31.3±0.9 e 31.1±0.1 g L-1 and to immobilized cells were 26.9±0.6; 29.1±0.3 e 29.5±0.8 g L-1 to the first, second and third sequential cycles, respectively. The propionic acid productivity was major in the first cycle to free cells (0.48 g L-1 h-1). The major propionic acid yield was 0.409 g g-1 in the first cycle to free cells. Batch co-fermentations of glucose and glycerol were also conducted in two different mass ratios (1:1 and 2:1 glucose:glycerol) by P. acidipropionici free and immobilized in montmorillonite K10. The major propionic acid final concentration was got in glucose:glycerol 2:1 mass ratio co-fermentations by free cells (31.4±0.3 g L-1) while the minor final concentration was got with co-fermentation 1:1 mass ratio to immobilized cells (23.9±0.8 g L-1). Acetic acid was got only in co-fermentations 2:1 mass ratio to free (0.3±0.4 g L-1) and immobilized (1.1±0.2 g L-1) cells. The major propionic acid productivity was got in co-fermentations 2:1 mass ratio to free cells (0.45 g L-1 h-1). The major propionic acid yield was got in co-fermentations 2:1 mass ratio to free cells (0.412 g g-1). Only co-fermentations yield lactic acid and trehalose. The major lactic acid final concentration was got in co-fermentations 1:1 mass ratio to free cells (10.5±0.3 g L-1) and the minor final concentration was got in co-fermentations 2:1 mass ratio to free cells (0.9±0.6 g L-1). The major trehalose final concentration was got in co-fermentations 2:1 mass ratio to immobilized cells (12.1±0.1 g L-1) and the minor final concentration was got in co-fermentations 2:1 mass ratio to free cells (6.7±1.0 g L-1) / Doutorado / Engenharia de Processos / Doutora em Engenharia Quimica