Publicação
Antibiofilm effect of synthetic antimicrobial peptides on Gram-positive and Gram-negative bacteria
| Resumo: | Prosthetic joint infections (PJI) present a challenge in the field of orthopedics, affecting patient wellbeing, and the healthcare industry. In this context, biofilms composed of a tri-dimensional matrix attach to prosthetic surfaces and exhibit heightened antibiotic resistance and tolerance due to factors like restricted drug penetration, altered microbial metabolic states, hindered growth rates and recalcitrant infections. As a result, addressing biofilm-related infections often necessitates prolonged antibiotic regimens or even implant removal, both of which pose considerable challenges to patient recovery. Consequently, novel strategies are imperative to effectively manage PJI, and one such potential is antimicrobial peptides (AMPs) as a promising avenue for treatment. Antimicrobial peptides are small molecules characterized by their cationic nature and wide-ranging antimicrobial activity. Their capability to penetrate biofilm matrices, disrupt microbial membranes, and target persister cells, makes them a possible strategy for PJI management. AMPs have demonstrated potential in not only preventing the initiation of biofilms but also disassembling established biofilm structures and synergizing with conventional antibiotics. In this work, we aim to study the antibiofilm potential of newly designed cationic AMPs like PaMAP1.9, PaMAP2, PwAMP1B5, PyAMP1B5, PaDBS1R3, PaDBS1R7 and EcDBS1R4. Our results show that PaMAP1.9 displayed potential for biofilm inhibition only for E. coli strains. PaMAP2 showed a high affinity for S. epidermidis biofilms capable of inhibiting the biofilm formation even at sub-inhibitory concentrations and eradication, with low biofilm cell viability. PaDBS1R7 showed affinity, especially for P. aeruginosa, which was able to inhibit its biofilm at high concentrations. While PyAMP1B5 and PwAMP1B5 showed the most extended activity spectrum affecting in general both Gram-negative and Gram-positive bacteria, with both capable of inhibiting E. coli biofilms. In addition, PyAMP1B5 also was capable of inhibiting S. epidermidis biofilms, one of the most prominent and strong biofilms present in PJI. |
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| Autores principais: | Coelho, José Maria Ribeiro |
| Assunto: | Biofilmes Infeções de próteses Interações péptido-membrana Péptido antimicrobiano Teses de mestrado - 2024 |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | português |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Prosthetic joint infections (PJI) present a challenge in the field of orthopedics, affecting patient wellbeing, and the healthcare industry. In this context, biofilms composed of a tri-dimensional matrix attach to prosthetic surfaces and exhibit heightened antibiotic resistance and tolerance due to factors like restricted drug penetration, altered microbial metabolic states, hindered growth rates and recalcitrant infections. As a result, addressing biofilm-related infections often necessitates prolonged antibiotic regimens or even implant removal, both of which pose considerable challenges to patient recovery. Consequently, novel strategies are imperative to effectively manage PJI, and one such potential is antimicrobial peptides (AMPs) as a promising avenue for treatment. Antimicrobial peptides are small molecules characterized by their cationic nature and wide-ranging antimicrobial activity. Their capability to penetrate biofilm matrices, disrupt microbial membranes, and target persister cells, makes them a possible strategy for PJI management. AMPs have demonstrated potential in not only preventing the initiation of biofilms but also disassembling established biofilm structures and synergizing with conventional antibiotics. In this work, we aim to study the antibiofilm potential of newly designed cationic AMPs like PaMAP1.9, PaMAP2, PwAMP1B5, PyAMP1B5, PaDBS1R3, PaDBS1R7 and EcDBS1R4. Our results show that PaMAP1.9 displayed potential for biofilm inhibition only for E. coli strains. PaMAP2 showed a high affinity for S. epidermidis biofilms capable of inhibiting the biofilm formation even at sub-inhibitory concentrations and eradication, with low biofilm cell viability. PaDBS1R7 showed affinity, especially for P. aeruginosa, which was able to inhibit its biofilm at high concentrations. While PyAMP1B5 and PwAMP1B5 showed the most extended activity spectrum affecting in general both Gram-negative and Gram-positive bacteria, with both capable of inhibiting E. coli biofilms. In addition, PyAMP1B5 also was capable of inhibiting S. epidermidis biofilms, one of the most prominent and strong biofilms present in PJI. |
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