ITQB: MD - PhD Theses
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- Biology and Interactions of gut anaerobic spore-formersPublication . Correia Martins, Diogo; Serrano, Mónica; Henriques, Adriano; Xavier, Karina"The gastrointestinal tract of healthy humans harbors bacteria that are crucial for our health, nutrition and overall well-being. Approximately 50 to 60% of these bacteria are capable of producing resilient spores, which are the primary means of transmission from one host to another. A genomic signature of sporulation within the human intestinal microbiota includes 66 genes and is predominantly characterized by genes known to play a role in sporulation, including those encoding RNA polymerase sigma factors that regulate cell type-specific gene expression during this process. Notably, about 30% of these signature genes have no known role in sporulation, and in some cases, they encode products that bear no similarity to any previously identified proteins. In this study, we explore the function of some of these genes within the sporulation process, using Clostridioides difficile as a model organism."
- The composition and function of the spore surface in the human pathogen Clostridioides difficilePublication . Antunes, Wilson; Henriques, Adriano O.; Serrano, Mónica; Gonçalves, Carlos Penha"Clostridioides difficile is a gram positive, strict anaerobic, spore-forming bacterium. It can be found in several ecosystems, due to the existence of highly resistant forms, the endospores, however the vegetative form is commonly associated to the gastrointestinal tract, of different animal species. Hosts colonization takes place primarily by the oral route, through ingestion of spores and the main mode of transmission between hosts is via the oro-fecal route. At the same time, airborne transmission and hosts contamination may occur via nasal-oral route, however this alternative route of infection is still under discussion, being only accepted by a minority of authors.(...)"
- Carbapenem Resistance in Clostridioides difficilePublication . Mendes, Aristides L.; Serrano, Mónica"Clostridioides difficile is a strict anaerobic, Gram-positive spore-forming bacterium and the leading cause of hospital acquired antibiotic associated diarrhoea. The development of antibiotic resistances by this bacterium is a serious threat. In the past, epidemic outbreaks of this bacterium occurred because of the acquisition of resistance against fluoroquinolones, one of the most used antibiotics in hospitals. Nowadays, there have been reports of acquisition of resistance against other antibiotics.(...)"
- Insights into the production of toxins and the assembly of spores in Clostridioides difficilePublication . Ramalhete, Sara; Henriques, Adriano Oliveira; Serrano, Mónica"Clostridioides difficile, a strict anaerobe, sporeforming bacterium, is a major nosocomial pathogen, causing a range of intestinal conditions linked to antibiotic therapy. Because of the number of infections and deaths it causes yearly, the high recurrence rates, the spreading at the community level and the risk of zoonotic transmission, it is classified as an urgent threat by the Centres for Disease Control and Prevention (CDC). Toxins and spores, two of the most important virulence factors in C. difficile, are key elements to determine the severity of the disease and the spreading of the infection, respectively.(...)"
- Assembly of the Clostridioides difficile spore surface layersPublication . Marini, Eleonora; Henriques, Adriano O."Clostridioides difficile is a strict, anaerobic, gram-positive spore-forming bacterium and the leading cause, worldwide, of hospital acquired antibiotic associated diarrhea. It causes a range of intestinal conditions whose symptoms include mild diarrhea but also more serious and potentially life-threatening conditions including pseudomembranous colitis, toxin megacolon, bowel perforation and sepsis. The C. difficile infection cycle begins with the ingestion of spores. Once ingested, spores can germinate in the small intestine in response to bile salts, leading to the formation of a population of cells able to produce the two main virulence factors, the cytotoxins TcdA and TcdB, and more spores. Shedding of the oxygen-resistant spores into the environment allows dissemination of the organism and the infection of new hosts. (...)"
- Single cell analysis of toxinogenesis by vegetative and sporulating cells in the enteric pathogen Clostridioides difficilePublication . Cassona, CP; Henriques, Adriano; Serrano, Mónica"Clostridium difficile, recently re-classified as Clostridioides difficile, is a strict anaerobe, with the ability to form spores. C. difficile is also a major nosocomial enteric pathogen worldwide and the cause of severe gastrointestinal conditions that can lead to death. The oxygenresistant spores allow host-host transmission, but also persistence of the organism in the host and the environment, being linked to disease recurrence. The last two decades have witnessed the emergence of epidemic strains that increased the incidence of C. difficile infection (CDI) associated with more severe symptoms and high recurrence rates.(...)"
- Determinants for the subcellular localization of the inner and outer spore coat hubs in Bacillus subtilisPublication . Nunes, Filipa Andreia Portugal; Henriques, Adriano; Serrano, MónicaEndospores, or spores for simplicity, are a highly resistant cell type produced by some bacterial species under adverse conditions. Two main protective layers contribute to the resilience of spores: the cortex, composed of peptidoglycan, and the outermost proteinaceous coat. In Bacillus subtilis, the coat comprises up to 80 different proteins, organized into four sublayers: the basement layer, the inner coat, the outer coat and the crust. These proteins are synthesized at different times during sporulation and deposited at the spore surface in multiple coordinated waves. Central to coat formation is a group of morphogenetic proteins that guide the assembly of the coat components. Targeting of the coat proteins to the surface of the developing spore is mainly controlled by the SpoIVA morphogenetic ATPase. In a second stage, the coat proteins fully encircle the spore, a process termed encasement that requires the morphogenetic protein SpoVID. Assembly of the inner coat requires SafA, whereas formation of the outer coat and the crust requires CotE. SafA interacts directly with the N terminus of SpoVID. (...)
- Assembly and function of a protein cross-linking enzyme during bacterial spore morphogenesisPublication . Fernandes, Catarina Gonçalves; Henriques, Adriano OliveiraSporulation in Bacillus subtilis culminates with the formation of a dormant endospore. The endospore (or spore) is one of the most resilient cell types known and can remain viable in the environment for extended periods of time. Contributing to the spore’s resistance and its ability to interact with and monitor its immediate environment is the coat, the outermost layer of B. subtilis spores. The coat is composed by over 70 different proteins, which are produced at different stages in sporulation and orderly assembled around the developing spore.(...)
- Spore differentiation in relation to the infectious cycle of the enteric pathogen Clostridium difficilePublication . Pereira, Maria de Fátima; Henriques, Adriano OliveiraClostridium difficile is a gram positive, spore former, anaerobic bacterium that is able to cause infection and disease, with symptoms ranging from mild diarrhea to pseudomembranous colitis, toxic megacolon, sepsis and death. In the last decade new strains have emerged that caused outbreaks of increased disease severity and higher recurrence, morbidity and mortality rates, and C. difficile is now considered both a main nosocomial pathogen associated with antibiotic therapy as well as a major concern in the community.(...)
- Dissecting the function of the SpoIIIJ and YqjG membrane protein insertases during bacterial spore developmentPublication . Côrte, Maria Luísa Gouveia e Freitas; Henriques, Adriano OliveiraSpoIIIJ and YqjG are the two members of the evolutionarily conserved YidC/Oxa1/Alb3 family of membrane protein insertases present in the Gram-positive bacterium Bacillus subtilis. Whilst either is capable of supporting viability, only SpoIIIJ is functional during sporulation, a carefully regulated developmental process that culminates in the formation of a dormant and highly resistant structure, the endospore. This partial functional overlap contrasts with the general picture of the family, for which trans-domain complementation is well documented.(...)