Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant <i>Staphylococcus aureus</i>
The discovery of new classes of antibiotics is slow, and it is being greatly outpaced by the development of bacterial resistance. This disparity places us in an increasingly vulnerable position because we are running out of safe and effective therapeutic options to treat antibiotic-resistant infecti...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/11/11/1550 |
| _version_ | 1797469315445817344 |
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| author | Junshu Yang Christopher Brown Wayland Noland Timothy J. Johnson Yinduo Ji |
| author_facet | Junshu Yang Christopher Brown Wayland Noland Timothy J. Johnson Yinduo Ji |
| author_sort | Junshu Yang |
| collection | DOAJ |
| description | The discovery of new classes of antibiotics is slow, and it is being greatly outpaced by the development of bacterial resistance. This disparity places us in an increasingly vulnerable position because we are running out of safe and effective therapeutic options to treat antibiotic-resistant infections. This is exemplified by the emergence and persistence of hospital-acquired and community-associated methicillin-resistant <i>S. aureus</i> (MRSA), which has markedly narrowed our options for treating life-threatening staph infections. Thus, there is an urgent need to develop novel, potent, preventive, and therapeutic agents. In our current study, we performed a whole-cell screening assay of synthetic libraries for antibacterial activity and identified a novel molecule, MZ-01. MZ-01 exhibited potent bactericidal activity against Gram-positive bacterial pathogens, including MRSA, <i>Streptococcus pyogenes</i>, and <i>Streptococcus pneumoniae,</i> at low concentrations. MZ-01 killed and lysed both the late exponential phase of an <i>S. aureus</i> population and bacteria inside mammalian cells. Furthermore, MZ-01 exhibited low cytotoxicity. These results indicate that MZ-01 is a promising scaffold to guide the development of novel, potent antibacterial agents against multidrug-resistant Gram-positive bacterial pathogens such as MRSA. |
| first_indexed | 2024-03-09T19:19:39Z |
| format | Article |
| id | doaj.art-01d5614b0ea54e33bfec0ac3375e6a4e |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T19:19:39Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-01d5614b0ea54e33bfec0ac3375e6a4e2023-11-24T03:28:14ZengMDPI AGAntibiotics2079-63822022-11-011111155010.3390/antibiotics11111550Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant <i>Staphylococcus aureus</i>Junshu Yang0Christopher Brown1Wayland Noland2Timothy J. Johnson3Yinduo Ji4Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USADepartment of Chemistry, University of Minnesota, Minneapolis, MN 55454, USADepartment of Chemistry, University of Minnesota, Minneapolis, MN 55454, USADepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USADepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USAThe discovery of new classes of antibiotics is slow, and it is being greatly outpaced by the development of bacterial resistance. This disparity places us in an increasingly vulnerable position because we are running out of safe and effective therapeutic options to treat antibiotic-resistant infections. This is exemplified by the emergence and persistence of hospital-acquired and community-associated methicillin-resistant <i>S. aureus</i> (MRSA), which has markedly narrowed our options for treating life-threatening staph infections. Thus, there is an urgent need to develop novel, potent, preventive, and therapeutic agents. In our current study, we performed a whole-cell screening assay of synthetic libraries for antibacterial activity and identified a novel molecule, MZ-01. MZ-01 exhibited potent bactericidal activity against Gram-positive bacterial pathogens, including MRSA, <i>Streptococcus pyogenes</i>, and <i>Streptococcus pneumoniae,</i> at low concentrations. MZ-01 killed and lysed both the late exponential phase of an <i>S. aureus</i> population and bacteria inside mammalian cells. Furthermore, MZ-01 exhibited low cytotoxicity. These results indicate that MZ-01 is a promising scaffold to guide the development of novel, potent antibacterial agents against multidrug-resistant Gram-positive bacterial pathogens such as MRSA.https://www.mdpi.com/2079-6382/11/11/1550antimicrobial agentsGram-positive bacterial pathogen<i>Staphylococcus aureus</i>MRSA |
| spellingShingle | Junshu Yang Christopher Brown Wayland Noland Timothy J. Johnson Yinduo Ji Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant <i>Staphylococcus aureus</i> Antibiotics antimicrobial agents Gram-positive bacterial pathogen <i>Staphylococcus aureus</i> MRSA |
| title | Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_full | Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_fullStr | Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_full_unstemmed | Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_short | Identification and Validation of a Novel Antibacterial Compound MZ-01 against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_sort | identification and validation of a novel antibacterial compound mz 01 against methicillin resistant i staphylococcus aureus i |
| topic | antimicrobial agents Gram-positive bacterial pathogen <i>Staphylococcus aureus</i> MRSA |
| url | https://www.mdpi.com/2079-6382/11/11/1550 |
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