Os nossos resultados, no que concerne a triagem de antimicrobianos e antibiofilmes, trazem uma abordagem promissora no combate a K. pneumoniae resistente a carbapenens bem como no combate a biofilmes formados por essa bactéria. De uma maneira geral, nossos dados mostraram que o peptídeo DJK-6 aumenta o potencial antimicrobiano e antibiofilme de antibióticos β-lactâmicos, como meropenem, imipenem e cefepima. Adicionalmente, mesmo que a arquitetura do biofilme seja construída, o peptídeo DJK-6 e meropenem juntos, podem eliminá-los de maneira eficiente.
Os resultados contrastantes obtidos entre os dois modelos de infeções, usando os peptídeos HHC-10 e IDR-1018, indicam caminhos para investigações acerca de variáveis que poderiam interferir no tratamento de infecções pulmonares com peptídeos catiônicos. Estudos específicos poderiam esclarecer como as diferenças experimentais impactaram os tratamentos antimicrobianos in vivo. Embora a combinação entre DJK-6 e meropenem, bem a utilização de outros peptídeos sozinhos (HHC-10 IDR-1018, IDR-1002), foi inefetiva em reduzir a carga bacteriana de K. pneumoniae suscetível ou resistente a carbapenens (considerando o modelo II de infecção), tais peptídeos poderiam ser utilizados na prevenção de biofilmes ou em abordagens antibiofilmes tópicas, no caso de IDR-1018 e DJK-6 (uma vez que os mesmos foram eficiente em reduzir ou erradicar biofilmes crescidos em superfícies de câmaras de fluxo).
Finalmente, sejam para combater bactérias resistentes ou biofilmes formados pelas mesmas, os resultados obtidos aqui, confirmam que peptídeos catiônicos pode ser um potencial agente terapêutico no tratamento de infecções bacterianas, principalmente quando utilizados como adjuvante de antibióticos. Ainda precisamos responder como DJK-6 contribui para o aumento da atividade de carbapenens e como isolados de K. pneumoniae resistem a ação de peptídeos, como IDR-1018 e HHC-10. Isso poderia indicar novos caminhos, utilizando peptídeos catiônicos, para sobrepor a resistência das tão temidas bactérias produtoras de KPC. A possibilidade de otimização das propriedades antimicrobianas, antibiofilmes, antiendotoxinas e imunomodulatórias, poderiam fazer dos peptídeos agentes eficientes no tratamento de infecções bacterianas.
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APÊNDICES
Apêndice A: Capítulos de livros
RIBEIRO, SM. Ensaios Antifungico. In: Octávio L. Franco, Clarissa P. da C. Gomes, Simoni