Bacterial biofilms can lead to chronic infections,increase tolerance to antibiotics and disinfectants,resistance to phagocytosis,and other components of the body’s immune system.Biofilm formation is implicated in the...Bacterial biofilms can lead to chronic infections,increase tolerance to antibiotics and disinfectants,resistance to phagocytosis,and other components of the body’s immune system.Biofilm formation is implicated in the persistence of staphylococcal infections and chronic Pseudomonas aeruginosa lung infections in cystic fibrosis(CF)patients(which can result from biofilm-growing mucoid strains).Conventional treatments utilize aggressive antibiotic prophylaxis/therapy to prevent/eliminate biofilms,followed by chronic suppressive therapy.Recently,the use of enzymes to dissolve the biofilm matrix was investigated,in addition to quorum sensing inhibitors to increase biofilm susceptibility to antibiotics.Here,we propose a novel strategy,utilizing ultrasound-induced inertial cavitation,to increase antibiotic efficacy.The wall shear stress at the biofilm interface is calculated,and viscoplastic constitutive equations are used to examine the biofilm response to the mechanical stress.Our simulations suggest that the maximum biofilm detachment occurs at high pressure/low frequency,and the mechanical disruption can affect the biochemical processes inside the biofilm resulting in vulnerability to antibiotics.展开更多
Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during syst...Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration.In this study,we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure–function relationship through one-factor modification.SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S.aureus.Moreover,SFK2 showed excellent biocompatibility in mice and piglet,and demonstrated significant therapeutic efficacy against S.aureus infection.In conclusion,our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S.aureus,providing a theoretical basis for developing targeted antimicrobial peptides.展开更多
基金the Natural Science and Engineering Research Council of Canada (NSERC) with a Discovery Grant (No.PGPIN-04772-2014)。
文摘Bacterial biofilms can lead to chronic infections,increase tolerance to antibiotics and disinfectants,resistance to phagocytosis,and other components of the body’s immune system.Biofilm formation is implicated in the persistence of staphylococcal infections and chronic Pseudomonas aeruginosa lung infections in cystic fibrosis(CF)patients(which can result from biofilm-growing mucoid strains).Conventional treatments utilize aggressive antibiotic prophylaxis/therapy to prevent/eliminate biofilms,followed by chronic suppressive therapy.Recently,the use of enzymes to dissolve the biofilm matrix was investigated,in addition to quorum sensing inhibitors to increase biofilm susceptibility to antibiotics.Here,we propose a novel strategy,utilizing ultrasound-induced inertial cavitation,to increase antibiotic efficacy.The wall shear stress at the biofilm interface is calculated,and viscoplastic constitutive equations are used to examine the biofilm response to the mechanical stress.Our simulations suggest that the maximum biofilm detachment occurs at high pressure/low frequency,and the mechanical disruption can affect the biochemical processes inside the biofilm resulting in vulnerability to antibiotics.
基金supported by the National Key R&D Program of China(2022YFD1300404)the National Natural Science Foundation of China(31930106 and U22A20514)+1 种基金the 2115 Talent Development Program of China Agricultural University(1041-00109019)the Pinduoduo-China Agricultural University Research Fund(PC2023A01001).
文摘Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration.In this study,we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure–function relationship through one-factor modification.SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S.aureus.Moreover,SFK2 showed excellent biocompatibility in mice and piglet,and demonstrated significant therapeutic efficacy against S.aureus infection.In conclusion,our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S.aureus,providing a theoretical basis for developing targeted antimicrobial peptides.
