Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> Infections
The emergence of multidrug-resistant strains requires the urgent discovery of new antibacterial drugs. In this context, an antibacterial screening of a subset of anthelmintic avermectins against gram-positive and gram-negative strains was performed. Selamectin completely inhibited bacterial growth a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/9/2242 |
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| author | Veronica Folliero Federica Dell’Annunziata Biagio Santella Emanuela Roscetto Carla Zannella Nicoletta Capuano Alessandro Perrella Anna De Filippis Giovanni Boccia Maria Rosaria Catania Massimiliano Galdiero Gianluigi Franci |
| author_facet | Veronica Folliero Federica Dell’Annunziata Biagio Santella Emanuela Roscetto Carla Zannella Nicoletta Capuano Alessandro Perrella Anna De Filippis Giovanni Boccia Maria Rosaria Catania Massimiliano Galdiero Gianluigi Franci |
| author_sort | Veronica Folliero |
| collection | DOAJ |
| description | The emergence of multidrug-resistant strains requires the urgent discovery of new antibacterial drugs. In this context, an antibacterial screening of a subset of anthelmintic avermectins against gram-positive and gram-negative strains was performed. Selamectin completely inhibited bacterial growth at 6.3 μg/mL concentrations against reference gram-positive strains, while no antibacterial activity was found against gram-negative strains up to the highest concentration tested of 50 μg/mL. Given its relevance as a community and hospital pathogen, further studies have been performed on selamectin activity against <i>Staphylococcus aureus</i> (<i>S. aureus</i>), using clinical isolates with different antibiotic resistance profiles and a reference biofilm-producing strain. Antibacterial studies have been extensive on clinical <i>S. aureus</i> isolates with different antibiotic resistance profiles. Mean MIC<sub>90</sub> values of 6.2 μg/mL were reported for all tested <i>S. aureus</i> strains, except for the macrolide-resistant isolate with constitutive macrolide-lincosamide-streptogramin B resistance phenotype (MIC<sub>90</sub> 9.9 μg/mL). Scanning Electron Microscopy (SEM) showed that selamectin exposure caused relevant cell surface alterations. A synergistic effect was observed between ampicillin and selamectin, dictated by an FIC value of 0.5 against methicillin-resistant strain. Drug administration at MIC concentration reduced the intracellular bacterial load by 81.3%. The effect on preformed biofilm was investigated via crystal violet and confocal laser scanning microscopy. Selamectin reduced the biofilm biomass in a dose-dependent manner with minimal biofilm eradication concentrations inducing a 50% eradication (MBEC<sub>50</sub>) at 5.89 μg/mL. The cytotoxic tests indicated that selamectin exhibited no relevant hemolytic and cytotoxic activity at active concentrations. These data suggest that selamectin may represent a timely and promising macrocyclic lactone for the treatment of <i>S. aureus</i> infections. |
| first_indexed | 2024-03-10T22:26:46Z |
| format | Article |
| id | doaj.art-1feffeefbb6c47d3b7715758f6bad7a0 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T22:26:46Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-1feffeefbb6c47d3b7715758f6bad7a02023-11-19T12:02:35ZengMDPI AGMicroorganisms2076-26072023-09-01119224210.3390/microorganisms11092242Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> InfectionsVeronica Folliero0Federica Dell’Annunziata1Biagio Santella2Emanuela Roscetto3Carla Zannella4Nicoletta Capuano5Alessandro Perrella6Anna De Filippis7Giovanni Boccia8Maria Rosaria Catania9Massimiliano Galdiero10Gianluigi Franci11Department of Medicine Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Medicine Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDivision Emerging Infectious Disease and High Contagiousness, Hospital D Cotugno, 80131 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Medicine Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Medicine Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyThe emergence of multidrug-resistant strains requires the urgent discovery of new antibacterial drugs. In this context, an antibacterial screening of a subset of anthelmintic avermectins against gram-positive and gram-negative strains was performed. Selamectin completely inhibited bacterial growth at 6.3 μg/mL concentrations against reference gram-positive strains, while no antibacterial activity was found against gram-negative strains up to the highest concentration tested of 50 μg/mL. Given its relevance as a community and hospital pathogen, further studies have been performed on selamectin activity against <i>Staphylococcus aureus</i> (<i>S. aureus</i>), using clinical isolates with different antibiotic resistance profiles and a reference biofilm-producing strain. Antibacterial studies have been extensive on clinical <i>S. aureus</i> isolates with different antibiotic resistance profiles. Mean MIC<sub>90</sub> values of 6.2 μg/mL were reported for all tested <i>S. aureus</i> strains, except for the macrolide-resistant isolate with constitutive macrolide-lincosamide-streptogramin B resistance phenotype (MIC<sub>90</sub> 9.9 μg/mL). Scanning Electron Microscopy (SEM) showed that selamectin exposure caused relevant cell surface alterations. A synergistic effect was observed between ampicillin and selamectin, dictated by an FIC value of 0.5 against methicillin-resistant strain. Drug administration at MIC concentration reduced the intracellular bacterial load by 81.3%. The effect on preformed biofilm was investigated via crystal violet and confocal laser scanning microscopy. Selamectin reduced the biofilm biomass in a dose-dependent manner with minimal biofilm eradication concentrations inducing a 50% eradication (MBEC<sub>50</sub>) at 5.89 μg/mL. The cytotoxic tests indicated that selamectin exhibited no relevant hemolytic and cytotoxic activity at active concentrations. These data suggest that selamectin may represent a timely and promising macrocyclic lactone for the treatment of <i>S. aureus</i> infections.https://www.mdpi.com/2076-2607/11/9/2242<i>Staphylococcus aureus</i>antimicrobial resistancedrug repurposinganthelmintic drugsmacrolidesbiofilm |
| spellingShingle | Veronica Folliero Federica Dell’Annunziata Biagio Santella Emanuela Roscetto Carla Zannella Nicoletta Capuano Alessandro Perrella Anna De Filippis Giovanni Boccia Maria Rosaria Catania Massimiliano Galdiero Gianluigi Franci Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> Infections Microorganisms <i>Staphylococcus aureus</i> antimicrobial resistance drug repurposing anthelmintic drugs macrolides biofilm |
| title | Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> Infections |
| title_full | Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> Infections |
| title_fullStr | Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> Infections |
| title_full_unstemmed | Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> Infections |
| title_short | Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> Infections |
| title_sort | repurposing selamectin as an antimicrobial drug against hospital acquired i staphylococcus aureus i infections |
| topic | <i>Staphylococcus aureus</i> antimicrobial resistance drug repurposing anthelmintic drugs macrolides biofilm |
| url | https://www.mdpi.com/2076-2607/11/9/2242 |
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