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Internalization, distribution, and activity of peptide H2 against the intracellular multidrug-resistant bovine mastitis-causing bacterium Staphylococcus aureus.

ABSTRACT: Bovine mastitis is mainly caused by Staphylococcus aureus, which is difficult to eliminate, prone to escape from antibacterial agents, and may cause recurring infections due to the intracellular nature of its infection and multidrug resistance. In this study, the intracellular activities of the NZ2114 derivative peptide H18R (H2) against methicillin-resistant S. aureus (MRSA) and multidrug-resistant bovine S. aureus strains were investigated in bovine mammary epithelial MAC-T cells and mouse mammary glands. The minimum inhibitory concentrations of H2 against S. aureus were 0.5?1??g/ml; H2 displayed a lower cytotoxicity than its parental peptide NZ2114 (survival rates of MAC-T cells: 100% [H2 treatment] vs 60.7% [NZ2114 (256??g/ml) treatment]). H2 was internalized into MAC-T cells mainly via clathrin-mediated endocytosis, and distributed in the cytoplasm. The intracellular inhibition rates against MRSA ATCC43300, the mastitis isolates S. aureus CVCC 3051 and E48 were above 99%, 99%, and 94%, respectively; these were higher than those in case of vancomycin (23-47%). In the mouse model of S. aureus E48-induced mastitis, after treatment with 100??g of H2 and vancomycin, bacterial numbers in each mammary gland were reduced by 3.96- and 1.59-log CFU, respectively. Additionally, similar to NZ2114 and vancomycin, H2 alleviated the histopathological damage of the mammary tissue and polymorphonuclear neutrophil infiltration in the alveoli. These results suggest that H2 can be used as a safe and effective candidate for treating S. aureus-induced mastitis.

SUBMITTER: Wang X

PROVIDER: S-EPMC6538662 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Internalization, distribution, and activity of peptide H2 against the intracellular multidrug-resistant bovine mastitis-causing bacterium Staphylococcus aureus.

Wang Xiao X Teng Da D Wang Xiumin X Hao Ya Y Chen Huixian H Mao Ruoyu R Wang Jianhua J

Scientific reports 20190528 1

Bovine mastitis is mainly caused by Staphylococcus aureus, which is difficult to eliminate, prone to escape from antibacterial agents, and may cause recurring infections due to the intracellular nature of its infection and multidrug resistance. In this study, the intracellular activities of the NZ2114 derivative peptide H18R (H2) against methicillin-resistant S. aureus (MRSA) and multidrug-resistant bovine S. aureus strains were investigated in bovine mammary epithelial MAC-T cells and mouse mam ...[more]

PMID: 31138863

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Project description:Staphylococcus aureus is a serious human and animal pathogen threat exhibiting extraordinary capacity for acquiring new antibiotic resistance traits in the pathogen population worldwide. The development of fast, affordable and effective diagnostic solutions capable of discriminating between antibiotic-resistant and susceptible S. aureus strains would be of huge benefit for effective disease detection and treatment. Here we develop a diagnostics solution that uses Matrix-Assisted Laser Desorption/Ionisation-Time of Flight Mass Spectrometry (MALDI-TOF) and machine learning, to identify signature profiles of antibiotic resistance to either multidrug or benzylpenicillin in S. aureus isolates. Using ten different supervised learning techniques, we have analysed a set of 82 S. aureus isolates collected from 67 cows diagnosed with bovine mastitis across 24 farms. For the multidrug phenotyping analysis, LDA, linear SVM, RBF SVM, logistic regression, naïve Bayes, MLP neural network and QDA had Cohen's kappa values over 85.00%. For the benzylpenicillin phenotyping analysis, RBF SVM, MLP neural network, naïve Bayes, logistic regression, linear SVM, QDA, LDA, and random forests had Cohen's kappa values over 85.00%. For the benzylpenicillin the diagnostic systems achieved up to (mean result ± standard deviation over 30 runs on the test set): accuracy = 97.54% ± 1.91%, sensitivity = 99.93% ± 0.25%, specificity = 95.04% ± 3.83%, and Cohen's kappa = 95.04% ± 3.83%. Moreover, the diagnostic platform complemented by a protein-protein network and 3D structural protein information framework allowed the identification of five molecular determinants underlying the susceptible and resistant profiles. Four proteins were able to classify multidrug-resistant and susceptible strains with 96.81% ± 0.43% accuracy. Five proteins, including the previous four, were able to classify benzylpenicillin resistant and susceptible strains with 97.54% ± 1.91% accuracy. Our approach may open up new avenues for the development of a fast, affordable and effective day-to-day diagnostic solution, which would offer new opportunities for targeting resistant bacteria.

Dataset Information

Internalization, distribution, and activity of peptide H2 against the intracellular multidrug-resistant bovine mastitis-causing bacterium Staphylococcus aureus.

Publications

Internalization, distribution, and activity of peptide H2 against the intracellular multidrug-resistant bovine mastitis-causing bacterium Staphylococcus aureus.

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