Repurposing Sitafloxacin, Prulifloxacin, Tosufloxacin, and Sisomicin as Antimicrobials Against Biofilm and Persister Cells of Pseudomonas aeruginosa
Pseudomonas aeruginosa is a ubiquitous bacterium found in hospitals and the surrounding environment. The ability of P. aeruginosa to form biofilms confers high-level resistance to antibiotics, and the persister cells formed in the presence of high antibacterial drug concentrations make P. aeruginosa...
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| Veröffentlicht in: | Current microbiology 2022-01, Vol.79 (1), p.12-12, Article 12 |
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| creator | She, Pengfei Li, Shijia Liu, Yaqian Xu, Lanlan Zhou, Linying Zeng, Xianghai Li, Yimin Liu, Shasha Li, Zehao Hussain, Zubiar Wu, Yong |
| description | Pseudomonas aeruginosa
is a ubiquitous bacterium found in hospitals and the surrounding environment. The ability of
P. aeruginosa
to form biofilms confers high-level resistance to antibiotics, and the persister cells formed in the presence of high antibacterial drug concentrations make
P. aeruginosa
-related infections more refractory. Further, there rarely is an effective antimicrobial alternative when biofilm- and persister cell-targeting treatment fails. Using a high-throughput screening assay, we previously identified fluoroquinolones sitafloxacin, prulifloxacin, and tosufloxacin as well as aminoglycoside sisomicin among FDA-approved drugs with significant bactericidal activity against
P. aeruginosa
. In addition, in our current study, these antibiotics exhibited an effective time- and dose-dependent eradication effects against the preformed biofilms of
P. aeruginosa
at the concentrations of 2–4 μM. These agents also exhibited bactericidal efficacy against CCCP-induced
P. aeruginosa
persister cells with the viable cell count decreased from 9.14 log10 CFU/mL to 6.15 (sitafloxacin), 7.59 (prulifloxacin), 4.27 (tosufloxacin), and 6.17 (sisomicin) log10 CFU/mL, respectively, following 4 h of treatment. Furthermore, sisomicin was also effective against conventional antibiotics induced persister cells in a time-dependent manner within 24 h. In addition, we confirmed the in vivo anti-biofilm efficacy of the identified antibiotics in a subcutaneous implantation biofilm-related infection model. Tosufloxacin exhibited the greatest in vivo bactericidal activity against
P. aeruginosa
biofilms with a reduction of 4.54 ΔLog10 CFU/mL compared to the vehicle group, followed by prulifloxacin, sitafloxacin, and sisomicin. Taken together, our results indicate that sitafloxacin, prulifloxacin, tosufloxacin, and sisomicin have great potential as alternatives for the treatment of refractory infections caused by
P. aeruginosa
biofilms and persister cells. |
| doi_str_mv | 10.1007/s00284-021-02729-w |
| format | Article |
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is a ubiquitous bacterium found in hospitals and the surrounding environment. The ability of
P. aeruginosa
to form biofilms confers high-level resistance to antibiotics, and the persister cells formed in the presence of high antibacterial drug concentrations make
P. aeruginosa
-related infections more refractory. Further, there rarely is an effective antimicrobial alternative when biofilm- and persister cell-targeting treatment fails. Using a high-throughput screening assay, we previously identified fluoroquinolones sitafloxacin, prulifloxacin, and tosufloxacin as well as aminoglycoside sisomicin among FDA-approved drugs with significant bactericidal activity against
P. aeruginosa
. In addition, in our current study, these antibiotics exhibited an effective time- and dose-dependent eradication effects against the preformed biofilms of
P. aeruginosa
at the concentrations of 2–4 μM. These agents also exhibited bactericidal efficacy against CCCP-induced
P. aeruginosa
persister cells with the viable cell count decreased from 9.14 log10 CFU/mL to 6.15 (sitafloxacin), 7.59 (prulifloxacin), 4.27 (tosufloxacin), and 6.17 (sisomicin) log10 CFU/mL, respectively, following 4 h of treatment. Furthermore, sisomicin was also effective against conventional antibiotics induced persister cells in a time-dependent manner within 24 h. In addition, we confirmed the in vivo anti-biofilm efficacy of the identified antibiotics in a subcutaneous implantation biofilm-related infection model. Tosufloxacin exhibited the greatest in vivo bactericidal activity against
P. aeruginosa
biofilms with a reduction of 4.54 ΔLog10 CFU/mL compared to the vehicle group, followed by prulifloxacin, sitafloxacin, and sisomicin. Taken together, our results indicate that sitafloxacin, prulifloxacin, tosufloxacin, and sisomicin have great potential as alternatives for the treatment of refractory infections caused by
P. aeruginosa
biofilms and persister cells.</description><identifier>ISSN: 0343-8651</identifier><identifier>EISSN: 1432-0991</identifier><identifier>DOI: 10.1007/s00284-021-02729-w</identifier><identifier>PMID: 34905092</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aminoglycoside antibiotics ; Aminoglycosides ; Anti-Bacterial Agents - pharmacology ; Anti-Infective Agents ; Antibiotics ; Antiinfectives and antibacterials ; Antimicrobial agents ; Bactericidal activity ; Biofilms ; Biomedical and Life Sciences ; Biotechnology ; Dioxolanes ; Drug Repositioning ; Fluoroquinolones ; Fluoroquinolones - pharmacology ; High-throughput screening ; Life Sciences ; Microbial Sensitivity Tests ; Microbiology ; Naphthyridines ; Piperazines ; Pseudomonas aeruginosa ; Sisomicin ; Time dependence ; Tosufloxacin</subject><ispartof>Current microbiology, 2022-01, Vol.79 (1), p.12-12, Article 12</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-22681c74409d4adfd25eb0ad600e723164bc3710dfc3030109a7f34be7c955dd3</citedby><cites>FETCH-LOGICAL-c375t-22681c74409d4adfd25eb0ad600e723164bc3710dfc3030109a7f34be7c955dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00284-021-02729-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00284-021-02729-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34905092$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>She, Pengfei</creatorcontrib><creatorcontrib>Li, Shijia</creatorcontrib><creatorcontrib>Liu, Yaqian</creatorcontrib><creatorcontrib>Xu, Lanlan</creatorcontrib><creatorcontrib>Zhou, Linying</creatorcontrib><creatorcontrib>Zeng, Xianghai</creatorcontrib><creatorcontrib>Li, Yimin</creatorcontrib><creatorcontrib>Liu, Shasha</creatorcontrib><creatorcontrib>Li, Zehao</creatorcontrib><creatorcontrib>Hussain, Zubiar</creatorcontrib><creatorcontrib>Wu, Yong</creatorcontrib><title>Repurposing Sitafloxacin, Prulifloxacin, Tosufloxacin, and Sisomicin as Antimicrobials Against Biofilm and Persister Cells of Pseudomonas aeruginosa</title><title>Current microbiology</title><addtitle>Curr Microbiol</addtitle><addtitle>Curr Microbiol</addtitle><description>Pseudomonas aeruginosa
is a ubiquitous bacterium found in hospitals and the surrounding environment. The ability of
P. aeruginosa
to form biofilms confers high-level resistance to antibiotics, and the persister cells formed in the presence of high antibacterial drug concentrations make
P. aeruginosa
-related infections more refractory. Further, there rarely is an effective antimicrobial alternative when biofilm- and persister cell-targeting treatment fails. Using a high-throughput screening assay, we previously identified fluoroquinolones sitafloxacin, prulifloxacin, and tosufloxacin as well as aminoglycoside sisomicin among FDA-approved drugs with significant bactericidal activity against
P. aeruginosa
. In addition, in our current study, these antibiotics exhibited an effective time- and dose-dependent eradication effects against the preformed biofilms of
P. aeruginosa
at the concentrations of 2–4 μM. These agents also exhibited bactericidal efficacy against CCCP-induced
P. aeruginosa
persister cells with the viable cell count decreased from 9.14 log10 CFU/mL to 6.15 (sitafloxacin), 7.59 (prulifloxacin), 4.27 (tosufloxacin), and 6.17 (sisomicin) log10 CFU/mL, respectively, following 4 h of treatment. Furthermore, sisomicin was also effective against conventional antibiotics induced persister cells in a time-dependent manner within 24 h. In addition, we confirmed the in vivo anti-biofilm efficacy of the identified antibiotics in a subcutaneous implantation biofilm-related infection model. Tosufloxacin exhibited the greatest in vivo bactericidal activity against
P. aeruginosa
biofilms with a reduction of 4.54 ΔLog10 CFU/mL compared to the vehicle group, followed by prulifloxacin, sitafloxacin, and sisomicin. Taken together, our results indicate that sitafloxacin, prulifloxacin, tosufloxacin, and sisomicin have great potential as alternatives for the treatment of refractory infections caused by
P. aeruginosa
biofilms and persister cells.</description><subject>Aminoglycoside antibiotics</subject><subject>Aminoglycosides</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Infective Agents</subject><subject>Antibiotics</subject><subject>Antiinfectives and antibacterials</subject><subject>Antimicrobial agents</subject><subject>Bactericidal activity</subject><subject>Biofilms</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>Dioxolanes</subject><subject>Drug Repositioning</subject><subject>Fluoroquinolones</subject><subject>Fluoroquinolones - pharmacology</subject><subject>High-throughput screening</subject><subject>Life Sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbiology</subject><subject>Naphthyridines</subject><subject>Piperazines</subject><subject>Pseudomonas aeruginosa</subject><subject>Sisomicin</subject><subject>Time dependence</subject><subject>Tosufloxacin</subject><issn>0343-8651</issn><issn>1432-0991</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kU9rFTEUxYNY7LP6BVzIgBsXHXuTzL8s24dVodBHreuQmWQeKTPJM3dC9Xv4gb3tqz5w4SKEQ3735HIOY284fOAA7RkCiK4qQXA6rVDl_TO24pUUJSjFn7MVyEqWXVPzY_YS8Q6ACwX8BTuWlYIalFixXzdul9Muog_b4qtfzDjFH2bw4bTYpDz5g7yNmA_KBEs4xtmTLAwW52HxJFLsvZlIbo0PuBQXPo5-mh_5jUvocXGpWLuJmDgWG3TZxjkGcjAu5a0PEc0rdjSSiXv9dJ-wb5cfb9efy6vrT1_W51flINt6KYVoOj60VQXKVsaOVtSuB2MbANcKyZuqJ5CDHQcJEjgo046y6l07qLq2Vp6w93vfXYrfs8NFzx4H2s0EFzNq0Tzk3HQdEPruH_Qu5hRoO6JAdU1LkRIl9hTlgJjcqHfJzyb91Bz0g5fed6apM_3Ymb6nobdP1rmfnf078qckAuQeQHoKW5cOf__H9jeB56SK</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>She, Pengfei</creator><creator>Li, Shijia</creator><creator>Liu, Yaqian</creator><creator>Xu, Lanlan</creator><creator>Zhou, Linying</creator><creator>Zeng, Xianghai</creator><creator>Li, Yimin</creator><creator>Liu, Shasha</creator><creator>Li, Zehao</creator><creator>Hussain, Zubiar</creator><creator>Wu, Yong</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20220101</creationdate><title>Repurposing Sitafloxacin, Prulifloxacin, Tosufloxacin, and Sisomicin as Antimicrobials Against Biofilm and Persister Cells of Pseudomonas aeruginosa</title><author>She, Pengfei ; Li, Shijia ; Liu, Yaqian ; Xu, Lanlan ; Zhou, Linying ; Zeng, Xianghai ; Li, Yimin ; Liu, Shasha ; Li, Zehao ; Hussain, Zubiar ; Wu, Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-22681c74409d4adfd25eb0ad600e723164bc3710dfc3030109a7f34be7c955dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aminoglycoside antibiotics</topic><topic>Aminoglycosides</topic><topic>Anti-Bacterial Agents - 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Academic</collection><jtitle>Current microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>She, Pengfei</au><au>Li, Shijia</au><au>Liu, Yaqian</au><au>Xu, Lanlan</au><au>Zhou, Linying</au><au>Zeng, Xianghai</au><au>Li, Yimin</au><au>Liu, Shasha</au><au>Li, Zehao</au><au>Hussain, Zubiar</au><au>Wu, Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repurposing Sitafloxacin, Prulifloxacin, Tosufloxacin, and Sisomicin as Antimicrobials Against Biofilm and Persister Cells of Pseudomonas aeruginosa</atitle><jtitle>Current microbiology</jtitle><stitle>Curr Microbiol</stitle><addtitle>Curr Microbiol</addtitle><date>2022-01-01</date><risdate>2022</risdate><volume>79</volume><issue>1</issue><spage>12</spage><epage>12</epage><pages>12-12</pages><artnum>12</artnum><issn>0343-8651</issn><eissn>1432-0991</eissn><abstract>Pseudomonas aeruginosa
is a ubiquitous bacterium found in hospitals and the surrounding environment. The ability of
P. aeruginosa
to form biofilms confers high-level resistance to antibiotics, and the persister cells formed in the presence of high antibacterial drug concentrations make
P. aeruginosa
-related infections more refractory. Further, there rarely is an effective antimicrobial alternative when biofilm- and persister cell-targeting treatment fails. Using a high-throughput screening assay, we previously identified fluoroquinolones sitafloxacin, prulifloxacin, and tosufloxacin as well as aminoglycoside sisomicin among FDA-approved drugs with significant bactericidal activity against
P. aeruginosa
. In addition, in our current study, these antibiotics exhibited an effective time- and dose-dependent eradication effects against the preformed biofilms of
P. aeruginosa
at the concentrations of 2–4 μM. These agents also exhibited bactericidal efficacy against CCCP-induced
P. aeruginosa
persister cells with the viable cell count decreased from 9.14 log10 CFU/mL to 6.15 (sitafloxacin), 7.59 (prulifloxacin), 4.27 (tosufloxacin), and 6.17 (sisomicin) log10 CFU/mL, respectively, following 4 h of treatment. Furthermore, sisomicin was also effective against conventional antibiotics induced persister cells in a time-dependent manner within 24 h. In addition, we confirmed the in vivo anti-biofilm efficacy of the identified antibiotics in a subcutaneous implantation biofilm-related infection model. Tosufloxacin exhibited the greatest in vivo bactericidal activity against
P. aeruginosa
biofilms with a reduction of 4.54 ΔLog10 CFU/mL compared to the vehicle group, followed by prulifloxacin, sitafloxacin, and sisomicin. Taken together, our results indicate that sitafloxacin, prulifloxacin, tosufloxacin, and sisomicin have great potential as alternatives for the treatment of refractory infections caused by
P. aeruginosa
biofilms and persister cells.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34905092</pmid><doi>10.1007/s00284-021-02729-w</doi><tpages>1</tpages></addata></record> |
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| ispartof | Current microbiology, 2022-01, Vol.79 (1), p.12-12, Article 12 |
| issn | 0343-8651 1432-0991 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Aminoglycoside antibiotics Aminoglycosides Anti-Bacterial Agents - pharmacology Anti-Infective Agents Antibiotics Antiinfectives and antibacterials Antimicrobial agents Bactericidal activity Biofilms Biomedical and Life Sciences Biotechnology Dioxolanes Drug Repositioning Fluoroquinolones Fluoroquinolones - pharmacology High-throughput screening Life Sciences Microbial Sensitivity Tests Microbiology Naphthyridines Piperazines Pseudomonas aeruginosa Sisomicin Time dependence Tosufloxacin |
| title | Repurposing Sitafloxacin, Prulifloxacin, Tosufloxacin, and Sisomicin as Antimicrobials Against Biofilm and Persister Cells of Pseudomonas aeruginosa |
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