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Instituto Superior De Ciências Da Saúde Egas Moniz INSTITUTO SUPERIOR DE CIÊNCIAS DA SAÚDE EGAS MONIZ MESTRADO INTEGRADO EM CIÊNCIAS FARMACÊUTICAS INFEÇÕES HUMANAS POR AEROMONAS Trabalho submetido por Sara Patrícia Alves Morais para a obtenção do grau de Mestre em Ciências Farmacêuticas Trabalho orientado por Prof. Doutora Helena Barroso Outubro de 2013 Dedicatória Dedico esta monografia às pessoas mais importantes da minha vida: os meus queridos Pais e o meu grande Irmão. Obrigada por existirem. 3 Agradecimentos Embora a monografia seja, pela sua finalidade académica, um trabalho individual, esta, direta ou indiretamente reúne os contributos de várias pessoas. Por isso, não posso de deixar de manifestar os mais sinceros agradecimentos pelos incentivos e apoios em mais uma etapa da minha formação académica. À Prof. Doutora Helena Barroso, pela sua orientação, disponibilidade, solução de dúvidas, opiniões e críticas, essenciais na elaboração da monografia. O meu muito obrigada também pelo empenho na fase final da monografia que mesmo tendo imenso trabalho foi incansável e determinante para a sua realização. À Mestre Ana Pintão, pelas oportunidades e pela confiança que depositou em mim e por tudo o que me proporcionou. A todos os Professores do instituto pelo enriquecimento da minha formação académica e científica. Aos meus colegas mais próximos e em especial às minhas amigas Célia, Lara e Zaida pela amizade, apoio, incentivo, força, companheirismo e por todos os momentos que partilhámos. A todos os meus familiares pelo incentivo e apoio incondicional, em especial aos meus Pais e Irmão pela coragem, paciência, ajuda na superação dos obstáculos e sobretudo por acreditarem em mim e naquilo que faço. Obrigada por tornarem possível a concretização de mais uma etapa. Aos meus avós paternos e tio por estarem sempre comigo. O meu profundo e sentido agradecimento a todos vós. 4 Resumo As bactérias do género Aeromonas estão amplamente distribuídas no meio ambiente, especialmente no ecossistema aquático. Encontram-se implicadas em várias infeções animais e são cada vez mais reconhecidas como patogénicos humanos. Os diferentes tipos de infeção/doença humana que Aeromonas podem causar bem como o difícil diagnóstico clínico e identificação laboratorial, tornam esta bactéria uma grande preocupação para a comunidade médica. Tais infeções incluem as gastrointestinais, pele e tecidos moles, intra-abdominais, respiratórias, oculares, trato urinário, meningite e septicemia. Além das infeções, a problemática compreensão taxonómica e a complexa classificação, o crescente reconhecimento da sua patogénese, a indeterminada prevalência correta das infeções à escala global e o desenvolvimento de resistências a vários antibióticos tornam cada vez mais preponderante a investigação sobre esta bactéria. De forma a compreender o real papel de Aeromonas nas infeções humanas bem como toda a controvérsia que recai sobre esta bactéria, foi realizada uma ampla revisão sobre este emergente patogénico humano. Palavras–chave: Aeromonas, infeções, humanas, patogénico. 5 Abstract Aeromonas genus bacteria are widely spread in the environment, with special focus on aquatic ecosystems. They are the cause of several infections on animals and are, now more than ever, acknowledged as important human pathogens. Since this bacteria can cause different types of infections/diseases, clinical diagnosis is difficult, just as laboratory identification, making it a rising concern amid the medical community. Such infections include systems such as gastrointestinal, skin and soft tissues, intra-abdominal, respiratory, ocular, urinary tract, meningitis and sepsis. Besides the increasing infection incidence due to this genus, problematic and complex taxonomy and classification, increasing pathogenesis knowledge, undetermined infections prevalence at a global scale and resistance development to different antibiotic classes became motives to why the research on these bacteria is fundamental. As a way to better understand the role of Aeromonas on human infections as well as all controversy surrounding this theme a revision and compilation about this pathogen was performed. Key words: Aeromonas, infections, human, pathogen. 6 Índice Geral 1. Introdução ................................................................................................................ 11 2. Taxonomia e Classificação ...................................................................................... 12 3. Género Aeromonas .................................................................................................. 18 3.1. Habitat .............................................................................................................. 18 3.2. Caraterísticas Fenotípicas ................................................................................ 20 3.3. Caraterísticas Bioquímicas............................................................................... 22 4. Patogenicidade ......................................................................................................... 22 4.1. Fatores de Virulência ....................................................................................... 24 4.1.1. Estruturas da célula ................................................................................... 25 4.1.1.1. Cápsula e Lipopolissacarídeo ............................................................ 25 4.1.1.2. Camada S........................................................................................... 25 4.1.2. Toxinas ..................................................................................................... 26 4.1.2.1. Enterotoxinas ..................................................................................... 26 4.1.2.2. Hemolisinas ....................................................................................... 26 4.1.2.3. Toxina Shiga ..................................................................................... 27 4.1.3. Outras enzimas extracelulares .................................................................. 28 4.1.3.1. Lipase ................................................................................................ 28 4.1.3.2. Proteases ............................................................................................ 28 4.1.4. Sistemas de secreção ................................................................................ 29 4.1.5. Quorum sensing ........................................................................................ 31 4.1.6. Sideróforos ............................................................................................... 32 4.1.7. Adesinas ................................................................................................... 33 4.1.7.1. Adesinas filamentosas: Píli/Fímbrias ................................................ 33 4.1.7.2. Adesinas não filamentosas ................................................................ 34 4.1.8. Mobilidade ................................................................................................ 34 7 4.1.8.1. Flagelos ............................................................................................. 34 4.2. Processo de Invasão ......................................................................................... 35 5. Infeções Humanas ................................................................................................... 37 5.1. Gastrointestinais ............................................................................................... 38 5.2. Pele e tecidos moles ......................................................................................... 40 5.3. Intra-abdominais .............................................................................................. 44 5.4. Infeções respiratórias ....................................................................................... 47 5.5. Outras infeções ................................................................................................ 49 5.5.1. Trato urinário ............................................................................................ 49 5.5.2. Oculares .................................................................................................... 51 5.5.3. Meningite .................................................................................................. 53 5.6. Septicemia ........................................................................................................ 53 6. Epidemiologia ......................................................................................................... 56 7. Métodos de Deteção e Identificação ....................................................................... 58 7.1. Métodos Convencionais ................................................................................... 58 7.2. Métodos Moleculares ....................................................................................... 64 8. Tratamento ............................................................................................................... 67 8.1. Antibioterapia .................................................................................................. 67 8.1.1. Introdução aos Antibióticos ...................................................................... 67 8.1.2. Antibioterapia nas infeções por Aeromonas spp. ..................................... 68 8.1.3. Resistências aos Antibióticos em Aeromonas .......................................... 73 8.2. Outros Tratamentos .........................................................................................
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