Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has led to serious infections, especially in hospitals and clinics, where treatment and prevention have become more difficult due to the formation of biofilms. Owing to biofilm-derived antibiotic tolerance, the currently available traditional antibiotics have failed to treat MRSA infections. Hence, there is a urgent need to develop novel antibiotics for treating life-threatening MRSA infections. Lugdunin (cyclic peptide-1), a nonribosomal cyclic peptide produced by Staphylococcus lugdunensis, exhibits potent antimicrobial activity against MRSA. Amazingly, cyclic peptide-1 and its analogues cyclic peptide-11 and cyclic peptide-14 have the ability to disperse mature MRSA biofilms and show anti-clinical MRSA activity, including MRSA persister cells. In addition, these three cyclic peptide compounds have non-toxicity, lower hemolytic activity and lack of resistance development. Our results indicate that cyclic peptide-1, cyclic peptide-11, and cyclic peptide-14 have great potential as new antimicrobial drug candidates for the treatment of clinical MRSA infections.

Non-aureus staphylococci and mammaliicocci as a cause of mastitis in domestic ruminants: current knowledge, advances, biomedical applications, and future perspectives – a systematic review

“…This makes it difficult for many antimicrobials to reach the cells present in the deeper layers, leading to heterogeneous exposure to antimicrobials in biofilms. Cells in the deeper layers of biofilms can be exposed to subinhibitory concentrations of antimicrobials until they potentially encounter a lethal dose (Wei et al 2022 ). This gradual exposure activates the transcriptional response at low doses, potentially promoting antimicrobial resistance mechanisms (Pascu et al 2022 ; Wei et al 2022 ).…”

“…Cells in the deeper layers of biofilms can be exposed to subinhibitory concentrations of antimicrobials until they potentially encounter a lethal dose (Wei et al 2022 ). This gradual exposure activates the transcriptional response at low doses, potentially promoting antimicrobial resistance mechanisms (Pascu et al 2022 ; Wei et al 2022 ). Therefore, care should be taken when treating biofilms with antimicrobials with high resistance potential.…”

“…Therefore, care should be taken when treating biofilms with antimicrobials with high resistance potential. This can be achieved by choosing agents characterized by modes of action that reduce the likelihood of resistance development or by adopting combined therapies (i.e., multiple antimicrobial agents with different modes of action) to treat infections (Wei et al 2022 ).…”

On the Cyclization of Non‐cyclic Peptides for Biological Applications: Inspiration from Naturally Cyclic Peptides

“…Cyclic peptides can play a role in biofilm formation, enhancing bacterial survival and resistance to environmental stresses. [91] Cyclic peptides are involved in a communication process called quorum sensing that enables bacteria to monitor their population density by producing and detecting signaling molecules. [92] The antimicrobial activity of cyclic peptides produced in bacteria is of paramount importance for both bacterial competition and potential therapeutic application.…”

A review on the potential of antibacterial peptides to control biofilm resistance

“…Indolicidin and Cathelicidic (LL-37) a major role in preventing the development of P. aeruginosa biofilm. This process is done by down-regulation of transcription of the two main quorum sensing systems such as Rh 1 and Las [50]. Another mechanism that is used by antibacterial peptides to stop the creation of the biofilm is increasing the twitching motility of P. aeruginosa.…”