Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds
Lipophosphonoxins (LPPOs) represent a new group of membrane-targeting antibiotics. Three generations of LPPOs have been described: First-generation LPPOs, second-generation LPPOs, and LEGO-LPPOs. All three generations have a similar mode of bactericidal action of targeting and disrupting the bacteri...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/10/2395 |
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| author | Viktor Šebek Pavel Anzenbacher Dominik Rejman Alena Špičáková Milan Kolář |
| author_facet | Viktor Šebek Pavel Anzenbacher Dominik Rejman Alena Špičáková Milan Kolář |
| author_sort | Viktor Šebek |
| collection | DOAJ |
| description | Lipophosphonoxins (LPPOs) represent a new group of membrane-targeting antibiotics. Three generations of LPPOs have been described: First-generation LPPOs, second-generation LPPOs, and LEGO-LPPOs. All three generations have a similar mode of bactericidal action of targeting and disrupting the bacterial cytoplasmic membrane of prokaryotic cells, with limited effect on eukaryotic cells. First-generation LPPOs showed excellent bactericidal activity against Gram-positive species, including multiresistant strains. Second-generation LPPOs broaden the antibiotic effect also against Gram-negative bacteria. However, both first- and second-generation LPPOs lose their antibacterial activity in the presence of serum albumin. LEGO-LPPOs were found to be active against both Gram-positive and Gram-negative bacteria, have better selectivity as compared to first- and second-generation resistance to LEGO-LPPOs was also not observed, and are active even in the presence of serum albumin. Second-generation LPPOs have been studied as antimicrobial additives in bone cement and as nanofiber dressing components in the treatment of wound infections in mice. Second-generation LPPOs and LEGO-LPPOs were also tested to treat ex vivo simulated endodontic infections in dental root canals. The results of all these studies were encouraging and suggested further investigation of LPPOs in these indications. This paper aims to review and compile published data on LPPOs. |
| first_indexed | 2024-03-10T20:58:24Z |
| format | Article |
| id | doaj.art-21b569a949be47a5a5943445585ce010 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:58:24Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-21b569a949be47a5a5943445585ce0102023-11-19T17:43:54ZengMDPI AGPharmaceutics1999-49232023-09-011510239510.3390/pharmaceutics15102395Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial CompoundsViktor Šebek0Pavel Anzenbacher1Dominik Rejman2Alena Špičáková3Milan Kolář4Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicDepartment of Pharmacology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Fleming Square 542/2, 160 00 Prague, Czech RepublicDepartment of Pharmacology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicDepartment of Microbiology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicLipophosphonoxins (LPPOs) represent a new group of membrane-targeting antibiotics. Three generations of LPPOs have been described: First-generation LPPOs, second-generation LPPOs, and LEGO-LPPOs. All three generations have a similar mode of bactericidal action of targeting and disrupting the bacterial cytoplasmic membrane of prokaryotic cells, with limited effect on eukaryotic cells. First-generation LPPOs showed excellent bactericidal activity against Gram-positive species, including multiresistant strains. Second-generation LPPOs broaden the antibiotic effect also against Gram-negative bacteria. However, both first- and second-generation LPPOs lose their antibacterial activity in the presence of serum albumin. LEGO-LPPOs were found to be active against both Gram-positive and Gram-negative bacteria, have better selectivity as compared to first- and second-generation resistance to LEGO-LPPOs was also not observed, and are active even in the presence of serum albumin. Second-generation LPPOs have been studied as antimicrobial additives in bone cement and as nanofiber dressing components in the treatment of wound infections in mice. Second-generation LPPOs and LEGO-LPPOs were also tested to treat ex vivo simulated endodontic infections in dental root canals. The results of all these studies were encouraging and suggested further investigation of LPPOs in these indications. This paper aims to review and compile published data on LPPOs.https://www.mdpi.com/1999-4923/15/10/2395LipophosphonoxinsLPPOsantimicrobial resistanceantibiotics |
| spellingShingle | Viktor Šebek Pavel Anzenbacher Dominik Rejman Alena Špičáková Milan Kolář Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds Pharmaceutics Lipophosphonoxins LPPOs antimicrobial resistance antibiotics |
| title | Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds |
| title_full | Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds |
| title_fullStr | Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds |
| title_full_unstemmed | Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds |
| title_short | Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds |
| title_sort | lipophosphonoxins a novel group of broad spectrum antibacterial compounds |
| topic | Lipophosphonoxins LPPOs antimicrobial resistance antibiotics |
| url | https://www.mdpi.com/1999-4923/15/10/2395 |
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