Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets
Cathelicidin-BF, derived from the banded krait (Bungarus fasciatus), is a typically cationic, amphiphilic and α-helical antimicrobial peptide (AMP) with 30 amino acids that exerts powerful effects on multidrug-resistant (MDR) clinical isolates, including Pseudomonas aeruginosa, Acinetobacter baumann...
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fcimb.2017.00466/full |
| _version_ | 1818545832812609536 |
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| author | Cunbao Liu Bin Shan Jialong Qi Yanbing Ma |
| author_facet | Cunbao Liu Bin Shan Jialong Qi Yanbing Ma |
| author_sort | Cunbao Liu |
| collection | DOAJ |
| description | Cathelicidin-BF, derived from the banded krait (Bungarus fasciatus), is a typically cationic, amphiphilic and α-helical antimicrobial peptide (AMP) with 30 amino acids that exerts powerful effects on multidrug-resistant (MDR) clinical isolates, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, but whether it targets plasma membranes or intracellular targets to kill bacteria is still controversial. In the present study, we demonstrated that the disruption of bacterial membranes with high concentrations of cathelicidin-BF was the cause of bacterial death, as with conventional antibiotics at high concentrations. At lower concentrations, cathelicidin-BF did not cause bacterial plasma membrane disruption, but it was able to cross the membrane and aggregate at the nucleoid regions. Functional proteins of the transcription processes of P. aeruginosa and A. baumannii were affected by sublethal doses of cathelicidin-BF, as demonstrated by comparative proteomics using isobaric tags for relative and absolute quantification and subsequent gene ontology (GO) analysis. Analysis using the Kyoto Encyclopedia of Genes and Genomes showed that cathelicidin-BF mainly interferes with metabolic pathways related to amino acid synthesis, metabolism of cofactors and vitamins, metabolism of purine and energy supply, and other processes. Although specific targets of cathelicidin-BF must still be validated, our study offers strong evidence that cathelicidin-BF may act upon intracellular targets to kill superbugs, which may be helpful for further efforts to discover novel antibiotics to fight against them. |
| first_indexed | 2024-12-12T07:45:10Z |
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| id | doaj.art-839cb35f748543e68bc5806e3b8aa375 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-12T07:45:10Z |
| publishDate | 2017-11-01 |
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| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-839cb35f748543e68bc5806e3b8aa3752022-12-22T00:32:38ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882017-11-01710.3389/fcimb.2017.00466301852Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular TargetsCunbao Liu0Bin Shan1Jialong Qi2Yanbing Ma3Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaDepartment of Clinical Lab, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaCathelicidin-BF, derived from the banded krait (Bungarus fasciatus), is a typically cationic, amphiphilic and α-helical antimicrobial peptide (AMP) with 30 amino acids that exerts powerful effects on multidrug-resistant (MDR) clinical isolates, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, but whether it targets plasma membranes or intracellular targets to kill bacteria is still controversial. In the present study, we demonstrated that the disruption of bacterial membranes with high concentrations of cathelicidin-BF was the cause of bacterial death, as with conventional antibiotics at high concentrations. At lower concentrations, cathelicidin-BF did not cause bacterial plasma membrane disruption, but it was able to cross the membrane and aggregate at the nucleoid regions. Functional proteins of the transcription processes of P. aeruginosa and A. baumannii were affected by sublethal doses of cathelicidin-BF, as demonstrated by comparative proteomics using isobaric tags for relative and absolute quantification and subsequent gene ontology (GO) analysis. Analysis using the Kyoto Encyclopedia of Genes and Genomes showed that cathelicidin-BF mainly interferes with metabolic pathways related to amino acid synthesis, metabolism of cofactors and vitamins, metabolism of purine and energy supply, and other processes. Although specific targets of cathelicidin-BF must still be validated, our study offers strong evidence that cathelicidin-BF may act upon intracellular targets to kill superbugs, which may be helpful for further efforts to discover novel antibiotics to fight against them.http://journal.frontiersin.org/article/10.3389/fcimb.2017.00466/fullantimicrobial peptide pressurecathelicidin-BFintracellular targetsmultidrug-resistantPseudomonas aeruginosaAcinetobacter baumannii |
| spellingShingle | Cunbao Liu Bin Shan Jialong Qi Yanbing Ma Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets Frontiers in Cellular and Infection Microbiology antimicrobial peptide pressure cathelicidin-BF intracellular targets multidrug-resistant Pseudomonas aeruginosa Acinetobacter baumannii |
| title | Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets |
| title_full | Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets |
| title_fullStr | Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets |
| title_full_unstemmed | Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets |
| title_short | Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets |
| title_sort | systemic responses of multidrug resistant pseudomonas aeruginosa and acinetobacter baumannii following exposure to the antimicrobial peptide cathelicidin bf imply multiple intracellular targets |
| topic | antimicrobial peptide pressure cathelicidin-BF intracellular targets multidrug-resistant Pseudomonas aeruginosa Acinetobacter baumannii |
| url | http://journal.frontiersin.org/article/10.3389/fcimb.2017.00466/full |
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