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Activity modulation of the Escherichia coli F1FO ATP synthase by a designed ant...

Makowski, Marcin; Almendro-Vedia, Víctor G.; Domingues, Marco; Franco, Octavio L.; López-Montero, Iván; Melo, Manuel N.; Santos, Nuno C.

Most antimicrobial peptides (AMPs) exert their microbicidal activity through membrane permeabilization. The designed AMP EcDBS1R4 has a cryptic mechanism of action involving the membrane hyperpolarization of Escherichia coli, suggesting that EcDBS1R4 may hinder processes involved in membrane potential dissipation. We show that EcDBS1R4 can sequester cardiolipin, a phospholipid that interacts with several respir...



Insights into the mode of action of the two-peptide lantibiotic lichenicidin

Barbosa, Joana C.; Gonçalves, Sónia; Makowski, Marcin; Silva, Ítala Cristine; Caetano, Tânia; Schneider, Tanja; Mösker, Eva; Süssmuth, Roderich D.

Lantibiotics are promising candidates to address the worldwide problem of antibiotic resistance. They belong to a class of natural compounds exhibiting strong activity against clinically relevant Gram-positive bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Lichenicidin is a class II two-peptide lantibiotic. The presence of the two matu...


Lipid membrane-based therapeutics and diagnostics

Carvalho, Patricia; Makowski, Marcin; Domingues, Marco; Martins, Ivo C.; Santos, Nuno C.

Success rates in drug discovery are extremely low, and the imbalance between new drugs entering clinical research and their approval is steadily widening. Among the causes of the failure of new therapeutic agents are the lack of safety and insufficient efficacy. On the other hand, timely disease diagnosis may enable an early management of the disease, generally leading to better and less costly outcomes. Severa...


EcDBS1R4, an antimicrobial peptide effective against Escherichia coli with in v...

Makowski, Marcin; Felício, Mário Romão; Fensterseifer, Isabel C M; Franco, Octávio L; Santos, Nuno C.; Gonçalves, Sónia

Discovering antibiotic molecules able to hold the growing spread of antimicrobial resistance is one of the most urgent endeavors that public health must tackle. The case of Gram-negative bacterial pathogens is of special concern, as they are intrinsically resistant to many antibiotics, due to an outer membrane that constitutes an effective permeability barrier. Antimicrobial peptides (AMPs) have been pointed ou...


Mechanism of action and membrane selectivity of a novel antimicrobial peptide

Makowski, Marcin

O número crescente de bactérias patogénicas resistentes aos antibióticos convencionais é atualmente uma das maiores preocupações, quer social como cientificamente. Com este cenário, a procura de alternativas terapêuticas tornou-se uma tarefa de enorme importância. Neste contexto, a investigação dedicada a péptidos antimicrobianos (AMP – antimicrobial peptides) tem aumentado, principalmente devido ao facto desta...


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