In 2004, a new legislation made it possible to form three-dimensional properties. A three-dimensional property consists of a closed volume and unlike a traditional property; a three-dimensional property is defined both vertically and horizontally. The fact that a three-dimensional property consists of a closed volume means that it can erode a traditional property. A three-dimensional property can therefore be located on top of a traditional property. This has been proven to be useful in cases where there is a commercial mall with residential units on the roof. Whether the residences were already built on top of the mall before the legislation came or if they were added through new construction or remodeling after the legislation, the ability to create three-dimensional properties has been proven to be useful when separating two types of activities from each other. The hard part is to implement this in practice in a way that satisfies the effective management of each activity. This thesis aims to investigate the interaction measures that need to be resolved in a building that houses a mall with residences on the roof. Furthermore, this thesis will show the potential advantages of residences on top of a mall and any difficulties that projects of this nature can lead to and how they in that case can be resolved. Three case studies have been selected, as they all are malls with residences on the roof. The malls we have chosen to examine are Fältöversten, Kista Galleria and Mall of Scandinavia, all located in the Stockholm County. As a basis, reviews of existing literature in the field have been carried out. Besides literature, practical knowledge have also been gathered from numerous interviews with property owners, the National Land Survey and consultants working with three-dimensional properties. In order to create a three-dimensional property there are some special requirements, which only apply to three-dimensional properties, that need to be fulfilled. The specific requirements are mentioned in Chapter 3, 1 a § Real Property Formation Act, and include that the action must be justified by the establishment’s construction and use, and also that it leads to a more effective management or securing financing or execution of the establishment. Especially facility management seems to be a strong reason why three-dimensional property formation is used. Commercial managers who do not want to manage residential housings see it as a way to create a more effective management for the property. Another of the special requirements of three-dimensional properties is that the property must be ensured the necessary rights for it to function in an effective manner. How to solve these rights is different but the result is decided in the cadastral procedure when three-dimensional properties are formed. In principle, one can say that there are four different ways to solve these rights and it is through demarcation, formation rights of easements, formation of joint facility and use of the neighbor rules. The general perception of the participants we interviewed seems to be that jointly owned facilities is a solution that is rather not used because it means that you have to cooperate with another party when making decisions, which can have negative consequences for the effective administration. Ideally, they see that as much as possible of the technical supply is separated and only supplies one of the properties. Ideally, when you have two properties on top of one another they should be two entirely separate properties except for sharing the supporting structure. A number of the participating respondents in the interviews have a positive view of projects of this type and are confident that we will be seeing more of it in the future as it becomes more difficult to get hold of good buildable land in Stockholm. They think the positive aspects that residences on top of a mall bring, outweigh any difficulties and problems that may arise from it. We are positive that more malls will have residences on the roof; as it seems like the right way to develop traditional mall areas and make them more accessible and attractive. What we can recommend for projects of this type is to carefully consider what kind of rights the property needs to be ensured in the cadastral procedure to prevent future problems. / År 2004 kom en ny lag som gjorde det möjligt att bilda tredimensionella fastigheter. En sådan fastighet består av en sluten volym som, till skillnad från en traditionell fastighet, är avgränsad både vertikalt och horisontellt. Det faktum att en tredimensionell fastighet utgörs av en sluten volym innebär att den urholkar en traditionell fastighet. Det innebär att en tredimensionell fastighet är lokaliserad inom en traditionell fastighet. Detta har bland annat kommit visa sig vara användbart i de fall man har en byggnad bebyggd med en kommersiell galleria med bostäder på taket. Oavsett om bostäderna fanns på gallerian innan lagstiftningen kom eller om de tillkommit genom ny- eller tillbyggnad efteråt har möjligheten till tredimensionell fastighetsbildning visat sig användbar för att åtskilja två verksamheter från varandra. Det svåra blir att genomföra detta rent praktiskt på ett sätt som tillfredsställer en effektiv förvaltning för respektive verksamhet. Detta arbete har till syfte att utreda vilka samverkansåtgärder som måste lösas i en byggnad som huserar en galleria med bostäder på taket. Vidare har undersökts vilka potentiella fördelar som finns med bostäder på en galleria samt eventuella svårigheter som projekt av den här typen kan medföra och hur dessa i så fall lösts. Tre fallstudier har valts som alla är gallerior med bostäder på taket. De gallerior vi valt att undersöka är Fältöversten, Kista galleria och Mall of Scandinavia, alla belägna i Stockholms län. Som grund för arbetet har en genomgång av befintlig litteratur inom området genomförts. Utöver litteratur har praktisk kunskap inhämtats från ett flertal intervjuer med fastighetsägare, Lantmäteriet och konsulter verksamma inom tredimensionell fastighetsbildning. För att en tredimensionell fastighet ska få bildas krävs det att fastigheten uppfyller ett antal speciella krav, utöver de krav som ställs på en traditionell fastighet vid fastighetsbildning. De speciella kraven finns nämnda i 3 kap 1a § FBL och innefattar bland annat att åtgärden dels ska vara motiverad med hänsyn till anläggningens konstruktion och användning, dels att den leder till en mer ändamålsenlig förvaltning eller tryggar finansieringen eller utförandet av anläggningen. Just förvaltningen verkar vara en stark anledning till varför man väljer att tredimensionellt fastighetsbilda en fastighet. En kommersiell förvaltare som inte är intresserad av att förvalta bostäder ser det som ett sätt att skapa en mer ändamålsenlig förvaltning av fastigheten. Ett annat av de speciella villkoren för tredimensionella fastigheter är att fastigheten måste tillförsäkras de rättigheter som är nödvändiga för att den ska fungera på ett ändamålsenligt sätt. Hur man löser dessa rättigheter är olika men resultatet fastslås i förrättningen när den tredimensionella fastigheten bildas. I princip kan man säga att det finns fyra olika sätt att lösa dessa rättigheter på och det är genom gränsdragning, bildande av servitut, inrättande av gemensamhetsanläggning och användande av de grannerättsliga reglerna. Den generella uppfattningen hos de aktörer vi intervjuat verkar vara att gemensamhetsanläggningar är en lösning man helst inte använder sig av eftersom det innebär att man måste samarbeta med en annan part vid beslutsfattande, något som kan ha negativa konsekvenser för en effektiv förvaltning. Helst ser de att så mycket som möjligt av den tekniska försörjningen är åtskild och endast försörjer en av fastigheterna. Det optimala när man har två fastigheter ovanpå varandra verkar därför vara att det är två helt separata fastigheter så när som på den bärande konstruktionen. Ett flertal av de intervjuade personerna har en positiv bild av projekt av den här typen och är övertygade att vi kommer få se mer av det i framtiden allt eftersom det blir svårare att få tag på bra byggbar mark i Stockholm. De tror att det positiva som bostäder ovanpå en galleria medför väger tyngre än eventuella svårigheter och problem som kan uppstå i och med det. Vi ser positivt på att fler gallerior får bostäder på taket, det verkar som rätt sätt att utveckla traditionella galleriaområden och göra dem mer tillgängliga och attraktiva. Det vi kan rekommendera vid projekt av den här typen är att noga tänka efter vad en verksamhet behöver tillförsäkras för rättigheter redan under förrättningen för att förhindra framtida problem.

Vibrio cholerae é uma bactéria autóctone em ecossistemas aquáticos, os fatores responsáveis pela virulência podem contribuir com a patogenicidade, influenciados por fatores genéticos e ambientais. Considerando a importância de conhecer e monitorar o V. cholerae, o estudo pretende caracterizar isolados da especie e padronizar uma metodologia para detecção em amostras de água. Os isolados foram avaliados por metodologias clássicas e moleculares, para confirmar espécie. Também, foi avaliada a presença de genes de virulência, susceptibilidade aos antibióticos e resposta em modelo invertebrado. Tres marcadores moleculares foram avaliados por PCR quantitativa. Observou-se que setenta dos isolados pertenciam a espécie V. cholerae e mostraram variação na prevalência dos genes de virulência e ao perfil de suscetibilidade ao antibióticos. Mostrou uma influencia da temperatura e concentração do inoculo no modelo invertebrado. Os marcadores moleculares selecionados mostraram a viabilidade da metodologia proposta neste estudo pela alta especificidade e sensibilidade. / Vibrio cholerae is an autochthonous bacterium in aquatic ecosystems, factors responsible for virulence may contribute to pathogenicity, influenced by genetic and environmental factors. Considering the importance of knowing and monitoring V. cholerae, the study pretend to characterize selected isolates and to standardize a methodology for detection in water samples. The isolates were evaluated by classical and molecular methodologies to confirm species. Also, the presence of factors associated with virulence, antibiotics susceptibility and response in invertebrate model were evaluated. Three molecular markers were evaluated by quantitative PCR. It was observed that seventy of the isolates belonged to the V. cholerae species and showed a variation in the prevalence of the virulence genes and the antibiotic susceptibility profile. Also, showed an influence of the inoculum temperature and concentration on the invertebrate model. The selected molecular markers showed the viability of the methodology proposed in this study for the high specificity and sensitivity.

Vibrio cholerae é uma bactéria autóctone em ecossistemas aquáticos, os fatores responsáveis pela virulência podem contribuir com a patogenicidade, influenciados por fatores genéticos e ambientais. Considerando a importância de conhecer e monitorar o V. cholerae, o estudo pretende caracterizar isolados da especie e padronizar uma metodologia para detecção em amostras de água. Os isolados foram avaliados por metodologias clássicas e moleculares, para confirmar espécie. Também, foi avaliada a presença de genes de virulência, susceptibilidade aos antibióticos e resposta em modelo invertebrado. Tres marcadores moleculares foram avaliados por PCR quantitativa. Observou-se que setenta dos isolados pertenciam a espécie V. cholerae e mostraram variação na prevalência dos genes de virulência e ao perfil de suscetibilidade ao antibióticos. Mostrou uma influencia da temperatura e concentração do inoculo no modelo invertebrado. Os marcadores moleculares selecionados mostraram a viabilidade da metodologia proposta neste estudo pela alta especificidade e sensibilidade. / Vibrio cholerae is an autochthonous bacterium in aquatic ecosystems, factors responsible for virulence may contribute to pathogenicity, influenced by genetic and environmental factors. Considering the importance of knowing and monitoring V. cholerae, the study pretend to characterize selected isolates and to standardize a methodology for detection in water samples. The isolates were evaluated by classical and molecular methodologies to confirm species. Also, the presence of factors associated with virulence, antibiotics susceptibility and response in invertebrate model were evaluated. Three molecular markers were evaluated by quantitative PCR. It was observed that seventy of the isolates belonged to the V. cholerae species and showed a variation in the prevalence of the virulence genes and the antibiotic susceptibility profile. Also, showed an influence of the inoculum temperature and concentration on the invertebrate model. The selected molecular markers showed the viability of the methodology proposed in this study for the high specificity and sensitivity.

Handel är en central del av en stads funktion och utveckling. Den bidrar till stadsliv och lockar människor till staden. Köpcenter påverkar och formar städers handelssituation och är ofta placerade i städers centralare delar. Undersökningar visar dock att köpcenter står inför utmaningar som hotar att lämna tomma lokaler, vilket påverkar stadens stadsliv och drivkraft. I denna uppsats undersöks hur svenska kommuner kan påverka köpcenters markanvändning och resiliens. Resiliens är, bland annat, den egenskap eller process som beskriver möjligheter och flexibilitet till att förutse och svara på olika former av kriser i förhoppning om att vidareutvecklas. Kommuners möjlighet till påverkan diskuteras främst utifrån teorier kring handel, köpcenter och det fysiska planeringssystemet. De ger en samlad förståelse över ett köpcenters situation och gör det möjligt att analysera dem och deras resiliensstrategier. Inom ramen för studien har två fallstudier genomförts, den ena behandlar köpcentret Entré i Malmö som fallstudieobjekt och den andra behandlar Galleria Boulevard i Kristianstad. Analysen visar på hur omständigheter så som e-handel, konkurrens mellan köpcenter och samarbetet mellan kommun och ägare påverkar fallstudieobjekten och deras nivå av resiliens. Analysen visar att förståelse över köpcentrets situation är en viktig del i en resiliensstrategi samt att kommuner och ägare samverkar i viss mån, men utan större inverkan. Uppsatsen belyser att kommuner visar på en vilja att öka köpcenters resiliens men att beslut inte alltid baseras på relevanta underlags rekommendationer. Därtill visar uppsatsen indikationer på att lagar som reglerar den kommunala fysiska planeringen ibland hindrar kommunen från att hantera köpcenters resiliens. Slutligen antyder analysen att kommuners främsta verktyg för att hantera resiliens är det fysiska planeringsarbetet och kommunikation med viktiga aktörer kopplade till det aktuella köpcentret. Sammanfattningsvis verkar ansvaret för köpcenters resiliens ligga hos deras ägare, men att kommuner kan bidra genom en ökad flexibilitet.

Bacillus cereus est fréquemment associé à des toxi-infections alimentaires et peut être responsable de pathologies opportunistes sévères. Les facteurs d'adaptations de B. cereus chez l'hôte, liés à son pouvoir pathogène, sont encore inconnus. La capacité d'acquérir le fer lors d'une infection, est une importante réponse adaptative des bactéries, leur permettant de surmonter le manque de fer imposé par l'hôte. Nos travaux ont permis l'identification de nouveaux facteurs impliqués dans l'adaptation de B. cereus chez l'hôte, ainsi que la caractérisation d'une nouvelle protéine IlsA (Iron regulated leucine-rich surface protein) fortement exprimée in vivo. L'identification de ces facteurs a été réalisée à l'aide du système IVET (In Vivo Expression Technology), adapté à la souche B. cereus ATCC 14579 et analysé après infection chez la larve du lépidoptère Galleria mellonella. Ce système permet la détection des promoteurs activés de façon transitoire. L'analyse de la structure protéique d'IlsA, montre quatre domaines conservés: un peptide signal d'export N-terminal, un domaine NEAT potentiellement impliqué dans le transport du fer, suivi d'une région riche en leucine (LRR) susceptible d'interagir avec les protéines de l'hôte, et un domaine SLH de liaison à la surface bactérienne. La présence d'une boîte fur dans la région promotrice d'ilsA suggère une régulation dépendante du fer. Les analyses transcriptionnelles ont montré qu'ilsA est en effet, exprimé dans les conditions de carence en fer in vitro et in vivo. De plus, nous avons démontré qu'IlsA est localisée à la surface et qu'elle est nécessaire pour l'acquisition de fer à partir des protéines présentes chez l'hôte : l'hémoglobine, l'hème et la ferritine, et ceci en se liant directement avec elles. En outre, l'étude de la séquence protéique du domaine NEAT d'IlsA, suggère qu'il serait responsable de l'interaction avec l'hème. Par ailleurs, nous avons montré que l'inactivation d'ilsA affecte la survie et la virulence de B. cereus chez l'insecte, et chez les macrophages murins. Nos résultats indiquent qu'IlsA est un facteur d'adaptation essentiel pour l'acquisition de fer au cours de l'infection, contribuant à la pathogénie de B. cereus chez les invertébrés et vertébrés.

No description available.

No description available.

Vibrio anguillarum infects many fish species in aquaculture, reducing farm productivity and negatively impacting fish welfare. Deeper understanding of the biology of V. anguillarum, particularly during infections in vivo, will help to improve disease prevention and control. Thus, the aim of this thesis was to provide further insight into the infection biology of V. anguillarum with a view to identifying better ways to reduce the impact of this pathogen in aquaculture. Conventional studies on virulence, particularly those aiming to identify novel virulence factors, often employ transposon mutagenesis where the functions of individual genes in the bacterium are disrupted. These mutant libraries are screened to identify those with attenuated virulence, allowing subsequent identification of the gene responsible. Usually the native fish host would be used but such studies are increasingly difficult to perform due to regulations on vertebrate experiments and ethical concerns. As a result, alternative invertebrate hosts are now an important means to studying microbial infections, but few models have been assessed for bacterial pathogens of fish. In this thesis, larvae of the greater wax moth Galleria mellonella were evaluated as an alternative host to investigate V. anguillarum virulence. Wild-type V. anguillarum isolates killed larvae in a dose-dependent manner, replicated in the haemolymph, and larvae infected with a lethal dose of bacteria could be rescued by antibiotic therapy, thus indicating that V. anguillarum established an infection in G. mellonella. Crucially, virulence of 11 wild-type V. anguillarum isolates correlated significantly between larva and Atlantic salmon infection models, and studies with isogenic mutants knocked out for various virulence determinants revealed conserved roles for some in larva and fish infections, including the pJM1 virulence plasmid and rtxA toxin. Thereafter, 350 strains from a V. anguillarum random transposon insertion library were screened for attenuated virulence in G. mellonella. In total, 12 strains had reduced virulence and in these mutants the transposon had inserted into genes encoding several recognised and putative virulence factors, including a haemolytic toxin (vah1) and proteins involved in iron sequestration (angB/G and angN). Importantly, the transposon in one strain had inserted into an uncharacterised hypothetical protein. Preliminary investigations found this putative novel virulence factor to contain a GlyGly-CTERM sorting domain motif, with sequence similarity to VesB of Vibrio cholerae which is involved in post-translational processing of cholera toxin. Finally, three transposon insertion libraries were mass sequenced on a MiSeq platform to identify V. anguillarum genes lacking transposon insertions. These genes were assumed to be ‘required’ for viability in the conditions under which the mutants were selected, in this case tryptone soya agar. In total, 248 genes lacked a transposon insertion and were the putative ‘required’ genes, and these may be important chemotherapeutic targets for new approaches to combat V. anguillarum infections. This thesis has furthered our understanding of the biology of the important fish pathogen V. anguillarum using an ethically acceptable approach, and the findings may assist with new ways to reduce the burden of this bacterium in aquaculture.

Submitted by MIRIAN MARCOLAN DE MELLO null (marcolanmirian@yahoo.com.br) on 2016-02-16T08:13:42Z No. of bitstreams: 1 TESE Doutorado Mirian14_02_2016REPOSITÓRIO.pdf: 1649527 bytes, checksum: c26e5ed45e88f8a3889873caa917015a (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-02-17T13:45:10Z (GMT) No. of bitstreams: 1 mello_mm_dr_sjc.pdf: 1649527 bytes, checksum: c26e5ed45e88f8a3889873caa917015a (MD5) / Made available in DSpace on 2016-02-17T13:45:10Z (GMT). No. of bitstreams: 1 mello_mm_dr_sjc.pdf: 1649527 bytes, checksum: c26e5ed45e88f8a3889873caa917015a (MD5) Previous issue date: 2015-12-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Devido ao rápido aumento dos micro-organismos resistentes aos antibióticos e ao desenvolvimento limitado de novos agentes antimicrobianos, as infecções por bactérias Gram-negativas estão se tornando um desafio para os profissionais da saúde e uma ameaça para a saúde pública internacional. O objetivo desse estudo foi avaliar o efeito sinérgico dos antibióticos convencionais associados a terapia fotodinâmica antimicrobiana (PDT) no controle de Acinetobacter baumannii. Para realização desse trabalho, foram obtidos isolados clínicos de A. baumannii do Laboratório de Análises Clínicas Valeclin da cidade de São José dos Campos/SP, identificados pelo método de bioquimismo e submetidos ao teste de difusão em disco para verificar a sensibilidade antimicrobiana. Os isolados selecionados foram transferidos para o ICT/UNESP, onde foi realizado testes para determinação da Concentração Inibitória Mínima aos antibióticos Imipenem e Meropenem seguindo as normas da CLSI. Cepas sensíveis e resistentes aos antibióticos foram avaliadas quanto a sensibilidade in vitro à terapia fotodinâmica antimicrobiana. Além disso, foram testados os efeitos dos antibióticos convencionais, da PDT e da terapia combinada de antibióticos e PDT nas infecções experimentais induzidas em G. mellonella por isolados clínicos de A. baumannii resistentes aos antibióticos. Os resultados das terapias na infecção experimental foram avaliados por meio da curva de sobrevivência das lagartas de G. mellonella. Os dados dos testes in vitro foram submetidos à Análise de Variância e teste de Tukey. Os dados obtidos na curva de sobrevivência de G. mellonella foram analisados pelo método de Log-rank. Em todos os testes, foi considerado nível de significância de 5%. Nos resultados desse estudo, observou-se que o Laboratório Valeclin identificou 1,54% de amostras positivas para A. baumannii entre as 13.715 amostras clínicas analisadas em um período de 8 meses. Entre os isolados de A. baumannii, 58% demonstraram resistência aos antibióticos imipenem e meropenem por meio de teste de difusão em disco. A seguir 3 isolados clínicos sensíveis e 18 isolados resistentes a esses antibióticos foram selecionados para o presente estudo. O valor de CIM para os isolados sensíveis variou de ˂ 0,5 a 1µg/mL e para os isolados resistentes de 64 a >128µg/mL. A PDT in vitro reduziu o número de células de A. baumannii em todos os isolados testados, mas o percentual de redução foi dependente dos isolados analisados. Além disso, verificou-se nos testes in vivo, que o tratamento com PDT, antibióticos (Imipenem e Meropenem) e associação de PDT+Antibióticos resultaram na sobrevivência das lagartas de G. mellonella, porém sem efeito sinérgico. Conclui-se que a PDT teve ação antimicrobiana contra isolados clínicos de A. baumannii sensíveis e resistentes aos carbapenêmicos, mas não apresentou efeito sinérgico quando associada com antibióticos. / Due to the rapid growth of microorganisms resistant to antibiotics and the limited development of new antimicrobial agents, infections by Gram-negative bacteria are becoming a challenge for health professionals and a threat to international public health. The aim of this study was to evaluate the synergistic effect of conventional antibiotics associated with antimicrobial photodynamic therapy (PDT) in control of Acinetobacter baumannii. In order to conduct this project were obtained clinical isolates of A. baumannii at the Clinical Laboratory Valeclin situated in the city of São José dos Campos / SP, identified by bioquimismo method and submitted to disk diffusion test to verify the antimicrobial sensitivity. The selected isolates were transferred to the ICT / UNESP, which were conducted tests to determine the Minimum Inhibitory Concentration to Imipenem and Meropenem antibiotics following the rules of the CLSI. Sensitive and resistant strains to antibiotics were evaluated in vitro sensitivity to antimicrobial photodynamic therapy. Besides, the effects of conventional antibiotics, and combined PDT, and PDT of antibiotics in experimental infections induced in G. mellonella by clinical isolates of A. baumannii resistant to antibiotic therapy were tested. The results of therapies in experimental infection were evaluated by survival curve of worms G. mellonella. Data from in vitro tests were submitted to ANOVA and Tukey test. The data obtained in G. mellonella survival curve were analyzed by log-rank method. In all tests it was considered 5% significance level. The results of this study, it was observed that the Valeclin Laboratory identified 1.54% of positive samples for A. baumannii between the 13,715 clinical specimens analyzed in a period of 8 months. Among the isolates of A. baumannii, 58% were resistant to antibiotic imipenem and meropenem by disk diffusion test. Next, 3 isolates clinical sensitive and 18 isolates resistant to those antibiotics were selected for this study. The MIC value for sensitive isolates ranged from 0.5 to ˂ 1μg / mL and resistant isolates from 64 to> 128μg / mL. The PDT in vitro reduced the number of A. baumannii cells in all isolates tested, but the percentage of reduction was dependent on the analyzed isolates. Furthermore, it was found in in vivo tests, treatment with PDT, antibiotic (Imipenem and Meropenem) and PDT + Antibiotics association resulted in the survival of G. mellonella caterpillars, but no synergistic effect. It was concluded that PDT has antimicrobial activity against clinical isolates of A. baumannii sensitive and resistant to carbapenems, but it had no synergistic effect when combined with antibiotics.

Uropathogenic E. coli (UPEC) is the most frequent cause of urinary tract infection (UTI), being responsible for up to 85% of community acquired and 40% of nosocomial cases. UPEC strains harbour various virulence factors that contribute to their ability to cause disease. The high prevalence across the globe of multidrug resistant UPEC is a significant threat to therapy. Virulent and resistant UPEC strains have been recognised as belonging to major lineages and we have only recently begun to understand the factors contributing to their successful global dissemination. Work in this thesis was carried out to identify the population structure of E. coli isolates recovered from urosepsis and biliary sepsis, to reveal any differences in genetic background. A total of 100 isolates from the blood and urine of 50 patients presenting with urosepsis and 27 isolates from cases of biliary sepsis were subjected to genotypic and phenotypic analysis, including MLST, virulence gene detection and antibiogram and metabolic profiling. Urosepsis paired isolates showed identical genotypes and antimicrobial resistance profiles. However, several pairs of isolates showed discrepant metabolic activity profiles suggesting niche specific regulation of metabolism. Members of the ST131 clone were significantly associated with antibiotic resistance and ST38 isolates were associated with the highest level of metabolic activity. An in vivo infection model was used to investigate the virulence potential of isolates from the major UPEC lineages. Galleria mellonella larvae inoculated with ST69 and ST127 isolates showed significantly higher mortality rates than those infected with other strains. However, one isolate of ST127 (strain EC18) was avirulent and comparative genomic analyses with a single virulent ST127 strain revealed an IS1 mediated deletion in the O-antigen cluster in strain EC18, which is likely to explain the lack of virulence in the larvae and demonstrates the importance of this cell surface molecule in the model system. Finally, a total of 202 UPEC isolates were recovered from community and hospital urine samples from a tertiary care hospital in Riyadh, Saudi Arabia. Molecular epidemiological investigation of the strains was carried out to examine the overall UPEC population structure, for the first time in any part of Saudi Arabia. The most common lineages were ST131 (17.3%), ST73 (11.4%), ST38 (7.4%), ST69 (7.4%) and ST10 (6.4%). The findings highlight the successful spread of multidrug resistant, CTX-M positive ST38, ST131 and ST405 UPEC in Saudi Arabia. The high proportion (35%) of ESBL producing E. coli isolates is a particular concern and is driving frequent prescription of carbapenem antibiotics. A total of four isolates of ST38 were positive for aggR, which is a virulence marker of enteroaggregative E. coli (EAEC); ST38 strains that cause UTI but have an EAEC genetic background are becoming recognised as novel UPEC and this clonal group warrants further study.