Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms
Since they are difficult and sometimes impossible to treat, infections sustained by multidrug-resistant (MDR) pathogens, emerging especially in nosocomial environments, are an increasing global public health concern, translating into high mortality and healthcare costs. In addition to having acquire...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/1/80 |
| _version_ | 1797342748464906240 |
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| author | Silvana Alfei |
| author_facet | Silvana Alfei |
| author_sort | Silvana Alfei |
| collection | DOAJ |
| description | Since they are difficult and sometimes impossible to treat, infections sustained by multidrug-resistant (MDR) pathogens, emerging especially in nosocomial environments, are an increasing global public health concern, translating into high mortality and healthcare costs. In addition to having acquired intrinsic abilities to resist available antibiotic treatments, MDR bacteria can transmit genetic material encoding for resistance to non-mutated bacteria, thus strongly decreasing the number of available effective antibiotics. Moreover, several pathogens develop resistance by forming biofilms (BFs), a safe and antibiotic-resistant home for microorganisms. BFs are made of well-organized bacterial communities, encased and protected in a self-produced extracellular polymeric matrix, which impedes antibiotics’ ability to reach bacteria, thus causing them to lose efficacy. By adhering to living or abiotic surfaces in healthcare settings, especially in intensive care units where immunocompromised older patients with several comorbidities are hospitalized BFs cause the onset of difficult-to-eradicate infections. In this context, recent studies have demonstrated that quaternary ammonium compounds (QACs), acting as membrane disruptors and initially with a low tendency to develop resistance, have demonstrated anti-BF potentialities. However, a paucity of innovation in this space has driven the emergence of QAC resistance. More recently, quaternary phosphonium salts (QPSs), including tri-phenyl alkyl phosphonium derivatives, achievable by easy one-step reactions and well known as intermediates of the Wittig reaction, have shown promising anti-BF effects in vitro. Here, after an overview of pathogen resistance, BFs, and QACs, we have reviewed the QPSs developed and assayed to this end, so far. Finally, the synthetic strategies used to prepare QPSs have also been provided and discussed to spur the synthesis of novel compounds of this class. We think that the extension of the knowledge about these materials by this review could be a successful approach to finding effective weapons for treating chronic infections and device-associated diseases sustained by BF-producing MDR bacteria. |
| first_indexed | 2024-03-08T10:37:47Z |
| format | Article |
| id | doaj.art-ba3a1ea416244239b4e61803d1b6e313 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T10:37:47Z |
| publishDate | 2024-01-01 |
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| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ba3a1ea416244239b4e61803d1b6e3132024-01-26T18:06:57ZengMDPI AGPharmaceutics1999-49232024-01-011618010.3390/pharmaceutics16010080Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against BiofilmsSilvana Alfei0Department of Pharmacy, University of Genoa, Viale Cembrano, 4, 16148 Genova, ItalySince they are difficult and sometimes impossible to treat, infections sustained by multidrug-resistant (MDR) pathogens, emerging especially in nosocomial environments, are an increasing global public health concern, translating into high mortality and healthcare costs. In addition to having acquired intrinsic abilities to resist available antibiotic treatments, MDR bacteria can transmit genetic material encoding for resistance to non-mutated bacteria, thus strongly decreasing the number of available effective antibiotics. Moreover, several pathogens develop resistance by forming biofilms (BFs), a safe and antibiotic-resistant home for microorganisms. BFs are made of well-organized bacterial communities, encased and protected in a self-produced extracellular polymeric matrix, which impedes antibiotics’ ability to reach bacteria, thus causing them to lose efficacy. By adhering to living or abiotic surfaces in healthcare settings, especially in intensive care units where immunocompromised older patients with several comorbidities are hospitalized BFs cause the onset of difficult-to-eradicate infections. In this context, recent studies have demonstrated that quaternary ammonium compounds (QACs), acting as membrane disruptors and initially with a low tendency to develop resistance, have demonstrated anti-BF potentialities. However, a paucity of innovation in this space has driven the emergence of QAC resistance. More recently, quaternary phosphonium salts (QPSs), including tri-phenyl alkyl phosphonium derivatives, achievable by easy one-step reactions and well known as intermediates of the Wittig reaction, have shown promising anti-BF effects in vitro. Here, after an overview of pathogen resistance, BFs, and QACs, we have reviewed the QPSs developed and assayed to this end, so far. Finally, the synthetic strategies used to prepare QPSs have also been provided and discussed to spur the synthesis of novel compounds of this class. We think that the extension of the knowledge about these materials by this review could be a successful approach to finding effective weapons for treating chronic infections and device-associated diseases sustained by BF-producing MDR bacteria.https://www.mdpi.com/1999-4923/16/1/80multidrug resistant (MDR) microorganismsbiofilmbiofilm life cycleanti-biofilm agentscationic antimicrobial agentsquaternary ammonium salts (QASs) |
| spellingShingle | Silvana Alfei Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms Pharmaceutics multidrug resistant (MDR) microorganisms biofilm biofilm life cycle anti-biofilm agents cationic antimicrobial agents quaternary ammonium salts (QASs) |
| title | Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms |
| title_full | Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms |
| title_fullStr | Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms |
| title_full_unstemmed | Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms |
| title_short | Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms |
| title_sort | shifting from ammonium to phosphonium salts a promising strategy to develop next generation weapons against biofilms |
| topic | multidrug resistant (MDR) microorganisms biofilm biofilm life cycle anti-biofilm agents cationic antimicrobial agents quaternary ammonium salts (QASs) |
| url | https://www.mdpi.com/1999-4923/16/1/80 |
| work_keys_str_mv | AT silvanaalfei shiftingfromammoniumtophosphoniumsaltsapromisingstrategytodevelopnextgenerationweaponsagainstbiofilms |