Interaction between mercury and selenium has previously been observed both in man and in animals. The aim of this work was to study expressions of interaction between mercury and selenium in human K-562 cells. Inorganic and organic forms of mercury and selenium were used and cells were either pre-treated with selenium or simultaneously exposed to selenium and mercury. Concentrations of selenium and mercury chosen were indicated by a study of growth inhibition in the individual compounds: a low concentration of selenium and selenomethionine induced slight cell growth inhibition, while a high concentration resulted in a notable growth inhibition. Two mercury concentrations were chosen: one with minimal toxicity and another with high cell toxicity. In addition, uptake and retention patterns of selenomethionine and selenite differed in both selenocompounds. All simultaneous treatments with 3.5 μM methylmercury produced a reduction in cellular mercury with increased selenium concentration. This was particularly obvious in selenite treatments. Growth curves from the simultaneous 3.5 μM methylmercury and selenite treatments indicated protection with increased selenite concentrations. In both exposure protocols, the 5 μM methylmercury treatments were toxic to the cells. In both study protocols, cells exposed to selenite and mercuric chloride manifested increased cellular mercury uptake with increased selenium concentration. In all selenite and 35 μM mercuric chloride treatments, no inhibition of growth was observed, while the 50 μM mercuric chloride treatments were toxic to the cells. Selenite-dependent protection was achieved in both exposure protocols when considering the cellular uptake of mercury. With few exceptions, selenomethionine produced similar effects as selenite on mercuric chloride uptake and growth inhibition.

Protective immunity against Plasmodium falciparum may be obtained after repeated exposure to infection. Several studies indicate that immunity against the blood stages of the P. Falciparum infection is mainly antibody mediated. Protective antibodies may act either on their own, mediate antibody-dependent phagocytosis and/or cell-mediated neutralization of parasites. This thesis describes several aspects of humoral immune responses to P. falciparum infection in individuals of different age groups, different genetic background and with different degrees of malaria exposure. Several target antigens for antibody-mediated inhibition of parasite growth or invasion have been identified. One such antigen is Pf332, which appears on the surface of parasitized erythrocytes at late trophozoite and schizont stage. This surface exposure makes the antigen a possible target for opsonizing antibodies. We optimized an in vitro assay for studying cellmediated parasite neutralization in the presence of Pf332-reactive antibodies. Our data demonstrate that, Pf332 specific antibodies are able to inhibit parasite growth on their own and in cooperation with human monocytes. The P. falciparum parasites have evolved several mechanisms to evade the host neutralizing immune responses. In this thesis, we show that freshly isolated P. falciparum parasites from children living in a malaria endemic area of Burkina Faso were less sensitive for growth inhibition in vitro by autologous immunoglobulins (Ig) compared with heterologous ones. Analyses of two consecutive isolates taken 14 days apart, with regard to genotypes and sensitivity to growth inhibition in vitro, did not give any clear-cut indications on possible mechanisms leading to a reduced inhibitory activity in autologous parasite/antibody combinations. The frequent presence of persisting parasite clones in asymptomatic children indicates that the parasite possesses as yet undefined mechanisms to evade neutralizing immune responses. Transmission reducing measures such insecticide treated nets (ITNs) have been shown to be effective in reducing morbidity and mortality from malaria. However, concerns have been raised that ITNs usage could affect the acquisition of malaria immunity. We studied the effect of the use of insecticide treated curtains (ITC) on anti-malarial immune responses of children living in villages with ITC since birth. The use of ITC did neither affect the levels of parasite neutralizing immune responses nor the multiplicity of infection. These results indicate that the use of ITC does not interfere with the acquisition of anti-malarial immunity in children living in a malaria hyperendemic area. There is substantial evidence that the African Fulani tribe is markedly less susceptible to malaria infection compared to other sympatrically living ethnic tribes. We investigated the isotypic humoral responses against P. falciparum asexual blood stages in different ethnic groups living in sympatry in two countries exhibiting different malaria transmission intensities, Burkina Faso and Mali. We observed higher levels of the total malaria-specific-IgG and its cytophilic subclasses in individuals of the Fulani tribe as compared to non-Fulani individuals. Fulani individuals also showed higher levels of antibodies to measles antigen, indicating that the intertribal differences are not specific for malaria and might reflect a generally activated immune system in the Fulani.

Background: The World Health Organization defines probiotics as ‘live microorganisms which, when administered in adequate amounts, confer a health benefit to the host’. Traditionally, probiotic microorganisms have been used to prevent or treat gastrointestinal tract diseases. In the last 15 years, there has been increasing interest of a possible probiotic impact on the oral microbiota and dental caries. Dental caries is a multifactorial disease, and the causative factor in the oral microbiota includes a shift from a balanced microflora to a microflora that includes more aciduric species such as mutans streptococci (MS), non-mutans streptococci, and Actinomyces. MS is considered an opportunistic pathogen although several other bacteria also contribute to the disease. Early acquisition of MS is associated with early development of caries; therefore a desirable complement to other prophylactic measures would be a MS colonization inhibitor. Objective: To better understand how selected strains of probiotic lactobacilli interact with MS in vitro and in vivo and to study the impact of probiotic lactobacilli on caries development during childhood. Material and methods: The in vitro properties of probiotic lactobacilli were studied with regard to (i) acid production from sugars and sugar alcohols, (ii) growth inhibition capacity on clinical isolates and reference strains of MS as well as Candida albicans and (iii) the capacity to co-aggregate with MS. A randomized controlled trial (RCT) tested the short-term effect of intervention with two Lactobacillus reuteri strains on MS, which was evaluated after treatment with chlorhexidine. The re-growth patterns of MS and 19 other selected strains were also evaluated. In the second clinical study  we investigated the long-term effect on MS prevalence and dental caries after an intervention with Lactobacillus paracasei ssp. paracasei F19 (LF19) between 4 and 13 months of age. Results: The results from the in vitro testing showed that strains of probiotic lactobacilli differed in their fermentation patterns, inhibition capacity and their capacity to co-aggregate, which should be kept in mind in the translation to clinical research. The clinical study on short-term effects of two L. reuteri strains on MS and other oral strains showed no effect on re-growth patterns after intervention. The clinical study on long-term effects of LF19 showed no effect on the prevalence of MS. Furthermore, the clinical follow-up at 9 years of age showed no differences in either decayed, missing, and filled surface (dmfs) or DMFS between the probiotic and placebo groups. Evaluation of saliva samples showed no signs of oral colonization with LF19 in the study group. Conclusion: The in vitro testing showed potentials of the selected probiotic Lactobacillus strains for interference with MS and C. albicans. The results from the clinical studies showed no such effect on MS or dental caries. Evidence regarding the effectiveness of specific probiotic applications in the prevention of dental caries is limited and does not allow for conclusions concerning the use of probiotic bacteria as a preventive measure.

Colorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. 15-lipoxygenase-1 (15-LO-1), an enzyme of the inflammatory eicosanoid pathway, oxidatively metabolizes linoleic acid and its expression is repressed in CRC. In the present study, the hypothesis that the lack of 15-LO-1 expression in CRC cells may contribute to the tumorigenesis was investigated. Therefore 15-LO-1 was introduced to colon cancer cell line HT-29 that does not have detectable levels of the 15-LO-1. The HT-29 cells were transiently transfected with the eukaryotic expression vector pcDNA3.1-15-LO-1 and the effects of 15-LO-1 expression on the proliferation, apoptosis as wells as metastatic potential of the cells were investigated. Cellular proliferation was analyzed by MTT assay and the apoptotic potential of 15-LO-1 was evaluated by acridine orange, floating cell ratio and caspase-3 assays as well as expression levels of the antiapoptotic protein XIAP. Cellular migration and invasion were investigated by Boyden chamber migration and Matrigel invasion assay.The data indicates that 15-LO-1 expression significantly decreased cell proliferation and increased apoptosis. In addition, a significant reduction was observed in migratory and invasive capacity 15-LO-1 expression also significantly reduced the expression of metastasis associated 1 protein (MTA-1). Taken together we propose that 15-LO-1 expression in CRC can inhibit colon cancer cell growth through induction of apoptotic cell death and may contribute to the inhibition of metastatic capacity in vitro which may be exploited for therapeutic purposes.

Das Spurengas Lachgas (N₂O) trägt zur Klimaerwärmung und Zerstörung der Ozonschicht in der Atmosphäre bei. Mit einem Anteil von ca. 70% sind landwirtschaftliche Böden weltweit Hauptverursacher der hohen anthropogenenN₂O Emissionen. N₂O entsteht in Böden durch verschiedene mikrobiologische Prozesse, bei denen N₂O unter anderem aus düngerbürtigem N gebildet wird. Die Entwicklung effektiver Minderungsmaßnahmen wird erst möglich, wenn ein Verständnis der N₂O Quellprozesse und ihrer Dynamik in Böden vorhanden ist. In dieser Studie wurde die Denitrifikation als ein Quellprozess untersucht, der zusammen mit Nitrifikation und Nitrifizierer-Denitrifikation hauptsächlich für die N₂O Emissionen aus Böden verantwortlich ist. Die Denitrifikation beschreibt die Reduktion von Nitrat (NO₃^-) zu N2, wobei Nitrit (NO₂^-), Stickstoffmonoxid (NO) und N₂O Zwischenprodukte dieses Reaktionsweges sind. Lange Zeit galten heterotrophe Bakterien als alleinige Verursacher von N₂O Emissionen aus der Denitrifikation. Im Jahr 1972 wurde allerdings in Versuchen mit Pilzreinkulturen nachgewiesen, dass auch Pilze in der Lage sind, N₂O über die Denitrifikation zu bilden. Zwei Jahrzehnte später wurde gezeigt, dass den meisten Pilzen das Enzym N₂O-Reduktase fehlt. Somit ist nicht N₂, sondern N₂O das hauptsächliche Endprodukt der pilzlichen Denitrifikation. Dies lässt vermuten, dass die Bildung von N₂O durch pilzliche Denitrifikation noch unterschätzt wird, vorausgesetzt Pilze und Bakterien haben ähnliche Prozessraten. Bisher wurde jedoch nicht ausgiebig erforscht, welchen Anteil die einzelnen mikrobiellen Gemeinschaften an der N₂O Bildung tatsächlich haben. Zur Unterscheidung der N₂O Bildungsprozesse in Bezug auf die beteiligten Mikroorganismen stellt die Isotopenanalyse von N₂O eine vielversprechende Anwendung dar. Vor allem die ¹⁵N-Positionspräferenz im N₂O (SP = site preference, d.h. die Differenz zwischen den δ¹⁵N-Werten der außenständigen und zentralen N-Atome im linearen N₂O-Molekül) aus der Denitrifikation zeigte starke Unterschiede zwischen Reinkulturen einiger Bakterien (SP = -11 bis 0 ‰) und zwei untersuchten Pilzen (SP ~ 37 ‰). Jedoch wurden Bakterienreinkulturen bisher ausgiebiger untersucht als Pilzreinkulturen, auch wenn bekannt ist, dass sich die beteiligten Enzyme bei der Denitrifikation, bis auf die NO-Reduktase, zwischen Bakterien und Pilzen nicht unterscheiden. Die verschiedenen NO-Reduktasen sind vermutlich die Ursache für die unterschiedlichen SP-Werte des von Pilzen und Bakterien produzierten N₂O. Des Weiteren wurde bei Bakterien ein Austausch der Sauerstoffatome von Zwischenprodukten der Denitrifikation und dem umgebenden Wasser gefunden, der zwischen 4 und 100% beträgt. Ob es einen solchen Sauerstoffaustausch auch bei Pilzen gibt, ist bisher jedoch unerforscht. Würde der Sauerstoffaustausch bei pilzlicher Denitrifikation nicht erfolgen, ermöglichte dies neben der unterschiedlichen SP eine weitere Unterscheidung der Herkunft des N₂O. Der Sauerstoffaustausch würde signifikante Unterschiede in der O Isotopensignatur im N₂O pilzlicher bzw. bakterieller Herkunft verursachen. In der vorliegenden Studie, die Aufschluss über die pilzliche N₂O Produktion aus der Denitrifikation geben soll, wurden drei Hauptthemen behandelt. In einem Isotopen-Tracerexperiment mit <up>18</sup>O-angereichertem Wasser wurde untersucht, ob bei sechs Pilzreinkulturen ein Sauerstoffaustausch zwischen Wasser und Zwischenprodukten der Denitrifikation stattfindet. Die Pilzreinkulturen zeigten tatsächlich durch Inkorporation von ¹⁸O aus Wasser in N₂O einen Sauerstoffaustausch. Auch Pilze können bis zu 100% des O während der Denitrifikation austauschen. Eine Unterscheidung zwischen der Denitrifikation durch Bakterien und Pilze anhand der Sauerstoffsignatur ist somit nicht möglich. Das zweite Thema sollte Auskunft darüber geben, ob hohe SP-Werte des N₂O aus der Denitrifikation bei Pilzreinkulturen allgemeingültig sind. Neben den zwei bisher untersuchten wurden vier weitere Pilzreinkulturen inkubiert. Diese Studie zeigte für die getesteten Pilzarten ebenfalls höhere SP-Werte (SP = 19.7 bis 32.6 ‰) im Vergleich zum Wertebereich von Bakterienreinkulturen. Basierend auf den Ergebnissen zum Sauerstoffaustausch aus dem Isotopen-Tracerexperiment wurde für die jeweiligen sechs Pilze, anhand der im Rahmen dieses Versuchs ermittelten natürlichen Sauerstoffisotopensignaturen, Mechanismen zur O Isotopenfraktionierung untersucht. Dafür wurden, neben den Werten des Sauerstoffaustausches und der natürlichen O Isotopensignatur der Pilzreinkulturen, Werte für Fraktionierungseffekte aus der Literatur in einem Isotopenfraktionierungsmodell angewendet, um die Beteiligung der verschiedenen Enzyme, die während der Denitrifikation an dem Sauerstoffaustausch beteiligt sind, abzuschätzen. Im Vergleich zu den NO₃^-- und NO-Reduktasen wies die N₂O^--Reduktase einen maßgeblich höheren Sauerstoffaustausch auf. Die Erkenntnisse aus den Experimenten mit den Pilzereinkulturen sollten im Rahmen des dritten Themas auf Ihre Übertragbarkeit auf die mikrobiellen Gemeinschaften in Böden untersucht werden, indem Bodeninkubationsversuche mit selektiver Hemmung der Organismengruppen (Pilze und Bakterien) durchgeführt wurden. Bei dieser Modifizierung der Methode zur Substrat-induzierten Respiration mit selektiver Hemmung (SIRIN) sollte untersucht werden, ob sich die spezifischen SP-Werte für Bakterien und Pilze nach selektiver Wachstumshemmung von Bodengemeinschaften durch spezifische Antibiotika nachweisen lassen. Die Ausprägung des Hemmungseffekts auf SP-Werte in den drei getesteten Böden entsprach nicht den Erwartungswerten, die sich aus den SP-Werten der Pilz- und Bakterienreinkulturen ergaben. Die ermittelten SP-Werte lagen in den meisten Fällen im Bereich jener bakterieller Reinkulturen und eine Hemmung der Bakterien führte in keinem Fall zu der erwarteten Veränderungen der SP-Werte. Folglich konnten die SP-Werte dieser Versuche nicht dazu dienen, die N₂O Bildung in den gehemmten Varianten den verschiedenen Organismengruppen zu zuordnen. Ungeklärt blieb, ob dies durch fehlende Eignung der modifizierten SIRIN-Methode zu erklären ist, oder ob die an Reinkulturen beobachteten SP-Unterschiede zwischen Pilzen und Bakterien nicht auf mikrobielle Gemeinschaften der Versuchsböden übertragbar sind. Im Hinblick auf nach wie vor bestehende methodische Defizite bei der Untersuchung der Pilzdenitrifikation im Boden sollte dies in weitergehenden Studien geklärt werden.

Microorganisms live in complex communities and interact either through secreting soluble molecules or by delivering effectors in a contact dependent manner. Microbial interactions range from cooperative to competitive. Contact-dependent growth inhibition (CDI), discovered in Escherichia coli EC93, is becoming increasingly studied, as this mode of interaction seems to be widespread among proteobacteria. CDI is mediated by cdiBAI genes which encode for a two-partner secretion system; i.e. CdiB is an outer membrane protein that transports CdiA to the surface of the cell. CdiA can interact with a specific receptor on a target cell and deliver a toxin localized in its C-terminal domain to the target cell. CdiI is a small immunity protein that neutralizes the toxic effect of CdiA toxin. Recently, evidence from our research group has shown that E. coli EC93 harbours two cdi loci. The first cdi locus has been extensively studied but the role of second locus remained unknown. In this study we wanted to elucidate the activity and the role of second E. coli EC93 cdi locus in intra-strain bacterial interactions. Bacterial competitions of E. coli EC93 wild type versus E. coli EC93 targets that had deletions for one or both cdi loci showed that the second locus is indeed active in inhibiting the targets, albeit to a lesser extent than the first. The toxic activity of the second cdi-locus was neutralized specifically by the second immunity protein. The expression of both these systems is higher under carbon starvation conditions than in nutrient rich conditions. Unfortunately, we could not elucidate the mechanism of toxicity for the second cdi locus toxin. Taken together, our results show that E. coli EC93 actively uses both of its cdi loci during bacterial interactions and that these systems are more active during stressful conditions.

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-03-23T16:29:21Z No. of bitstreams: 1 Yrlania de Lira Guerra.pdf: 709734 bytes, checksum: 3d0f17731c8fae1c2730d371c8128560 (MD5) / Made available in DSpace on 2017-03-23T16:29:21Z (GMT). No. of bitstreams: 1 Yrlania de Lira Guerra.pdf: 709734 bytes, checksum: 3d0f17731c8fae1c2730d371c8128560 (MD5) Previous issue date: 2013-02-26 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Brazil is a major producer of world agricultural production is limited by pests and diseases. Among the diseases Sclerotium rolfsii Sacc. is a fungus that causes major losses in agriculture by presenting more than 500 hosts and is present in all tropical regions. The effect of essential oils in control of wilt sclerotia, culture as having reference to the peanut crop, with subsequent recommendation in agricultural management, with a segment phytopathological. Using four different isolates of S. rolfsii was conducted mycelial growth rate, followed by the pathogenicity test in the peanut plants (cultivar BR 1), the SR5 was isolated which had the highest growth rate and more aggressive. The seven essential oils were selected for bioassay of inhibition at concentrations previously established, with the reference dosage of 1000 ppm. Being selected again at low concentrations, from 500 ppm, Palmarosa oil which was showed the highest inhibition rate of formation of sclerotia, the lowest dose tested that was 300 ppm. In the test of suppression of diffusion of oxalic acid was performed with the more aggressive isolated (SR5) with palmarosa oil at 400 ppm, which reduced the rate of mycelial growth by 55%. The bioassay establishment of the pathogen in the substrate and pathogenicity in peanut genotypes in a greenhouse with two genotypes, BR 1 and Senegal. The assay was performed with substrate Baseplant being added 40 g de P2O5 + 15 g KCl + 200 g de humus/kg substrate fertilized. BR Genotype 1 was more susceptible than Senegal, isolated SR5 was more aggressive, leading to higher rates of disease when grown only in substrate. In the validation assay of the oil against S. rolfsii in the greenhouse, was held with seven treatments and at the end of the cycle there was a weight gain of 54% of the pods, 57% in the number of pods/plant and harvest index of 40%. / O Brasil é um dos maiores produtores agrícolas mundiais do amendoim e sua produção é limitada por pragas e doenças. Dentre as doenças, destaca-se a murcha de esclerócio que causa grandes perdas na agricultura por apresentar mais de 500 hospedeiros e estar presente em todas as regiões tropicais. Avaliou-se o efeito dos óleos essenciais no controle da murcha de esclerócio tendo como cultura de referência ao amendoim. Foram testados quatro isolados de Sclerotium rolfsii avaliando-se a sua taxa de crescimento micelial em BDA (batata, dextrose e ágar) e patogenicidade no amendoim (cv. BR 1). O isolado SR5 foi o que apresentou a maior taxa de crescimento e o mais agressivo. Os sete óleos essenciais foram selecionados pela realização do bioensaio de inibição, com concentrações previamente estabelecidas, tendo como dosagem referencial 1000 ppm. Sendo novamente selecionados a baixas concentrações, a partir de 500 ppm. O óleo de Palmarosa foi o que apresentou a maior taxa de inibição de formação de esclerócios, na menor dose testada (300 ppm). O teste de supressão da difusão do ácido oxálico, foi realizado com o isolado mais agressivo (SR5), com o óleo de Palmarosa a 400 ppm, o qual reduziu a taxa de crescimento micelial em 55%. Para o teste de estabelecimento do patógeno no substrato Baseplant e de patogenicidade nos genótipos de amendoim em casa de vegetação utilizou-se dois genótipos, BR 1 e Senegal. O ensaio realizado com substrato recebeu adição de 40 g de P2O5 + 15 g KCl + 200 g de húmus/Kg como adubação básica. O genótipo BR 1, foi mais suscetível que Senegal, o isolado SR5 mostrou-se mais agressivo, provocando maior índice de doença quando cultivado apenas em substrato. O ensaio de validação do óleo contra S. rolfsii em casa de vegetação, foi realizado com sete tratamentos e ao final do ciclo da cultura observou-se um ganho de 54% no peso das vagens, 57% no número de vagens/planta e 40% no índice de colheita.

Thesis advisor: Babak Momeni / Microbial communities are complex networks comprised of multiple species that are facilitating and inhibiting one another (as well as themselves). Currently, we lack an understanding of what mechanisms drive coexistence within these communities. We aimed to remedy this by studying the dynamics of coexisting communities, focusing on the complexity of their interaction networks, the impact of spatial dynamics, and the interplay of facilitating and inhibiting interactions. These limitations in our understanding prevent the furtherment of designing intentional communities for bioremediation, maintenance of healthy microbiota, and other functional communities. To better understand these microbial dynamics, we chose to address the problem from two fronts: computational modeling and exploring dynamics of cocultures. Through our 1-D model, spatial structure fostering more coexistence – especially when facilitation is present. For the coexistence assays, we determined that contact-dependent growth inhibition is a density dependent mechanism, and the use of a Tn-Seq mutant library to predict species interactions is possible, but needs further optimization to reconcile density dependent effects of interactions. / Thesis (MS) — Boston College, 2021. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Phytochemicals are recognized as playing an important role in cancer prevention by fruits and vegetables. The avocado is a widely grown and consumed fruit that is high in nutrients and low in calories, sodium, and fats. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with chloroform from avocado fruits target multiple signaling pathways and increase intracellular reactive oxygen leading to apoptosis. This review summarizes the reported phytochemicals in avocado fruit and discusses their molecular mechanisms and targets. These studies suggest that individual and combinations of phytochemicals from the avocado fruit may offer an advantageous dietary strategy in cancer prevention.

Lower respiratory tract infectious diseases are a world-wide healthcare burden with bacterial pathogens accounting for a large portion of primary and secondary infections. The human respiratory tract is home to hundreds of species of microbes that comprise the human airway microbiome. These commensals play a crucial role in human health in part by providing colonization resistance against pathogens. In a previous study from the Surette lab it was shown that specific bacterial isolates from the respiratory microbiome inhibits the growth of pathogens aerobically. This included an isolate of Staphylococcus aureus which inhibited the growth of Enterococcus faecium. This activity was further characterized in this thesis and the underlying mechanism was explored through comparative genomics. As well, this observation provided proof-of-concept for a large-scale screen for additional isolates which inhibit pathogen growth. I hypothesized that the respiratory tract microbiota included many other bacteria capable of inhibiting the growth of respiratory tract pathogens in both aerobic and anaerobic environments, and that anaerobic conditions will identify new activities not detected aerobically. To examine and identify potential beneficial bacteria, I have screened ~5000 respiratory tract bacteria from the Surette lab’s airway isolate collection against four pathogens: Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae. The respiratory tract commensals were pinned onto the pathogen-lawn and their interaction was expressed as zones of clearing or altered growth phenotypes of the pathogen. The results of the screen showed that anti-pathogen activity was a common feature of respiratory tract commensals. In particular, S. pneumoniae was inhibited by taxonomically diverse members of the microbiota representing three phyla (Proteobacteria, Firmicutes and Actinobacteria). Many of the facultative anaerobes that inhibited S. pneumoniae expressed their activity in anerobic conditions. / Thesis / Master of Science (MSc) / The human respiratory tract harbours commensal and pathogenic bacteria, and the latter cause most of the lower respiratory tract infections. The commensal bacteria help to train the immune system and impede the growth of pathogens through colonization resistance. A previous study by the Surette lab identified bacterial isolates from the respiratory tract that inhibit the growth of select pathogens, among them, a particular strain of Staphylococcus aureus. Based on the results of the earlier study, I hypothesized that the respiratory tract bacteria is a good source of commensals that can inhibit the growth of S. aureus and other respiratory pathogens, such as Streptococcus pneumoniae, Pseudomonas aeruginosa and Klebsiella pneumoniae. To find potential therapeutic bacteria, I screened ~5000 respiratory tract isolates from the Surette lab’s strain collection for the ability to impair growth of target pathogens. Additionally, I further characterized the activity of the previously identified S. aureus strain against various Lactobacillalles strains and used comparative genomics to identify potential biosynthetic genes required for biosynthesis of molecules with antibacterial activity within the genome of S. aureus. The research reported in this thesis demonstrates that many commensal bacteria that live within our airways have the ability to inhibit the growth of bacterial pathogens. This work may provide a new source of antibiotics against respiratory infections and new strategies to reduce susceptibility to infections in vulnerable populations.