Quinolone resistance acquisition and impact on virulence in Salmonella enterica: a cost-benefit matter
[eng] Infections due to Salmonella enterica are of great concern worldwide as they represent an important cause of morbidity and mortality. Resistance to antibiotics used to treat salmonellosis has emerged along the years, and thus, the treatment of choice has been changing in order to adapt to the...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/102754 |
| Acceso en línea: | https://hdl.handle.net/2445/102754 http://hdl.handle.net/10803/396155 |
| Access Level: | acceso abierto |
| Palabra clave: | Salmonel·la Quinolones Virulència (Microbiologia) Salmonella Quinolone antibacterial agents Virulence (Microbiology) |
| Sumario: | [eng] Infections due to Salmonella enterica are of great concern worldwide as they represent an important cause of morbidity and mortality. Resistance to antibiotics used to treat salmonellosis has emerged along the years, and thus, the treatment of choice has been changing in order to adapt to the new features of the circulating pathogens causing disease. Currently, fluoroquinolones, mainly represented by ciprofloxacin and ofloxacin, are widely used to treat this kind of infections although other antimicrobial classes as well as new generations of fluoroquinolones are sometimes required when treatment failure occurs. This situation is mainly due to the rise in the number of isolates showing nalidixic acid resistance associated with a decrease in the susceptibility to fluoroquinolones (e.g. ciprofloxacin). Moreover, the spread of multidrug resistant isolates carrying several resistance plasmid or chromosomally-located determinants also explains, in part, the decrease in the efficacy of the current treatment and represents an important issue. Despite this trend, a low frequency of fluoroquinolone-resistant Salmonella enterica isolates are still reported in the literature, a fact that has been the object of attention in our research group. In order to explain the current scene, we have hypothesized a presumable link between quinolone-resistance acquisition and the decrease in the virulence features among this species. This PhD thesis addresses the context of Salmonella from different perspectives, including an epidemiological approach as well as in vitro models in order to understand the biology of this pathogen and its relation with quinolone resistance. In order to develop our hypothesis, the following specific objectives were defined: 1) Evaluation of the clonal relatedness of S. Enteritidis and S. Typhimurium clinical isolates using two different typing techniques, 2) Analysis of the outer-membrane subproteome of S. Typhimurium SL1344, 3) Investigation of the molecular mechanisms of quinolone resistance and their regulation, 4) Assessment of virulence-related properties in clinical and in vitro-selected mutants of Salmonella enterica isolates presenting different degrees of susceptibility/resistance to quinolones, 5) Identification of novel genes potentially involved in quinolone resistance and/or virulence in S. Typhimurium, 6) Genome comparison of S. Typhimurium isolates causing invasive versus non-invasive salmonellosis from different geographical areas. These objectives have been fulfilled in 5 papers, a manuscript and additional results. |
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