Dataset Information

An optimized antimicrobial peptide analog acts as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus.

ABSTRACT: The misuse of antibiotics in animal protein production has driven the emergence of a range of drug-resistant pathogens, which threaten existing public health security. Consequently, there is an urgent need to develop novel antimicrobials and new infection treatment options to address the challenges posed by the dramatic spread of antibiotic resistance. Piscidins, a class of fish-specific antimicrobial peptides (AMPs), are regarded as promising therapies for biomedical applications. Progress towards potential analogs from the piscidin family has been hampered by unenforceable structural optimization strategies. Here, we leverage a strategy of bioinformatics analysis combined with molecular dynamics (MD) simulation to identify specific functional hotspots in piscidins and rationally design related analogues. As expected, this approach yields a potent and non-toxic PIS-A-1 that can be used as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus (MRSA) pathogens. Remarkably, the structural optimization scheme and application strategy proposed here will contribute richer therapeutic options for the safe production of animal protein.

SUBMITTER: Chen X

PROVIDER: S-EPMC9744894 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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An optimized antimicrobial peptide analog acts as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus.

Chen Xuan X Wu Xiaoping X Wang Shaoyun S

NPJ science of food 20221212 1

The misuse of antibiotics in animal protein production has driven the emergence of a range of drug-resistant pathogens, which threaten existing public health security. Consequently, there is an urgent need to develop novel antimicrobials and new infection treatment options to address the challenges posed by the dramatic spread of antibiotic resistance. Piscidins, a class of fish-specific antimicrobial peptides (AMPs), are regarded as promising therapies for biomedical applications. Progress towa ...[more]

PMID: 36509755

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Project description:The chemotherapeutic options for methicillin-resistant Staphylococcus aureus (MRSA) infections are limited. Due to the multiple resistant MRSA, therapeutic failure has occurred frequently, even using antibiotics belonging to different categories in clinical scenarios, very recently. This study aimed to investigate the interactions between 11 antibiotics representing different mechanisms of action against MRSA strains and provide therapeutic strategies for clinical infections. Susceptibilities for MRSA strains were determined by broth microdilution or agar dilution according to CLSI guideline. By grouping with each other, a total of 55 combinations were evaluated. The potential synergism was detected through drug interaction assays and further investigated for time-killing curves and an in vivo neutropenic mouse infection model. A total of six combinations (vancomycin with rifampicin, vancomycin with oxacillin, levofloxacin with oxacillin, gentamycin with oxacillin, clindamycin with oxacillin, and clindamycin with levofloxacin) showed synergistic activity against the MRSA ATCC 43300 strain. However, antibacterial activity against clinical isolate #161402 was only observed when vancomycin combined with oxacillin or rifampicin in time-killing assays. Next, therapeutic effectiveness of vancomycin/oxacillin and vancomycin/rifampicin was verified by an in vivo mouse infection model inoculated with #161402. Further investigations on antimicrobial synergism of vancomycin plus oxacillin and vancomycin plus rifampicin against 113 wild-type MRSA strains were evidenced by combined antibiotic MICs and bacterial growth inhibition and in vitro dynamic killing profiles. In summary, vancomycin/rifampicin and vancomycin/oxacillin are the most potential combinations for clinical MRSA infection upon both in vitro and in vivo tests. Other synergetic combinations of levofloxacin/oxacillin, gentamycin/oxacillin, clindamycin/oxacillin, and clindamycin/fosfomycin are also selected but may need more assessment for further application.

Dataset Information

An optimized antimicrobial peptide analog acts as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus.

Publications

An optimized antimicrobial peptide analog acts as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus.

Similar Datasets

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