Loading…
Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections
Key Points When bacteria become quiescent (that is, slow growing or non-growing), they can avoid being killed by bactericidal antibiotics. This phenomenon extends the period of morbidity experienced by the patient and necessitates prolonged antibiotic treatment to achieve a cure. The effects of such...
Saved in:
| Published in: | Nature reviews. Microbiology 2011-01, Vol.9 (1), p.62-75 |
|---|---|
| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c635t-fdd2452ea818ab622dd7ae6b8e488b509ea1d62158521e2f9c07251e355fcf393 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c635t-fdd2452ea818ab622dd7ae6b8e488b509ea1d62158521e2f9c07251e355fcf393 |
| container_end_page | 75 |
| container_issue | 1 |
| container_start_page | 62 |
| container_title | Nature reviews. Microbiology |
| container_volume | 9 |
| creator | Hurdle, Julian G O'Neill, Alex J Chopra, Ian Lee, Richard E |
| description | Key Points
When bacteria become quiescent (that is, slow growing or non-growing), they can avoid being killed by bactericidal antibiotics. This phenomenon extends the period of morbidity experienced by the patient and necessitates prolonged antibiotic treatment to achieve a cure.
The effects of such bacteria are evident from several infections that typically contain these organisms, such as biofilm diseases, osteomyeletis and tuberculosis granuloma.
In the first decade of the new millenium, the discovery and development of antibiotics that target the function of the membrane have provided new paradigms with which to combat persisting bacteria.
In one approach, agents disorganize the structure and function of the membrane bilayer, causing subsequent multiple antibacterial effects in cells. Many of these membrane-active agents are reported to kill bacterial biofilms.
Moreover, agents that inhibit the function of bacterial respiratory and redox enzymes, thereby causing membrane depolarization and energy depletion, have been shown to kill dormant
Mycobacterium tuberculosis
.
The effects of membrane-active agents on quiescent cell types arise from the fact that all living bacteria require an intact, functional membrane and all living cells require energy to sustain their viability, even without growth.
Our understanding of slow-growing or non-growing bacteria has improved, as well as our knowledge about the mechanisms of membrane-acting agents. There are many opportunities for obtaining new classes of drugs based on our current understanding of the mechanisms behind these antimicrobials, as well as many challenges.
Infections involving slow-growing and persistent bacteria, including
Mycobacterium tuberculosis
and biofilms, are difficult to treat. Here, Hurdle and colleagues argue that developing antibiotics to target the bacterial membrane and membrane functions is a promising approach for the treatment for these difficult-to-treat infections.
Persistent infections involving slow-growing or non-growing bacteria are hard to treat with antibiotics that target biosynthetic processes in growing cells. Consequently, there is a need for antimicrobials that can treat infections containing dormant bacteria. In this Review, we discuss the emerging concept that disrupting the bacterial membrane bilayer or proteins that are integral to membrane function (including membrane potential and energy metabolism) in dormant bacteria is a strategy for treating persistent infection |
| doi_str_mv | 10.1038/nrmicro2474 |
| format | article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3496266</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A245393368</galeid><sourcerecordid>A245393368</sourcerecordid><originalsourceid>FETCH-LOGICAL-c635t-fdd2452ea818ab622dd7ae6b8e488b509ea1d62158521e2f9c07251e355fcf393</originalsourceid><addsrcrecordid>eNptks9vFSEQx4nR2Fo9eTdrPXjQVxdYWNaDSdP4K2nipZ4Jyw5bml14Amv0v3farc9X03CAMJ_5Mt9hCHlO6xNac_UupNnbFFnTNg_IIW2bekMFbx7uzkwekCc5X9U1E6Jlj8kBo1Q2gotDAhcmjVB8GKve2ALJm6maYe6TCVC5JdjiY3hfmVAtYYAEv7ZT9AUGhOylCT7PlYupKgnMjcoWUva5QCiVDw5u0vNT8siZKcOz2_2IfP_08eLsy-b82-evZ6fnGyu5KBs3DKwRDIyiyvSSsWFoDcheQaNUL-oODB0ko0IJRoG5ztYtExS4EM463vEj8mHV3S79DIPFKpKZ9Db52aTfOhqv70aCv9Rj_Kl500kmJQq8vhVI8ccCuejZZwvThN2IS9ZKdqLlQlEkj_8jr-KSArrTirZtq1gtEHq1QqOZQGM_Ir5qryX1KTrFirlUSJ3cQ-EaAH82BnAe7-8kvFkT8NtzTuB2Dmmtr2dC780E0i_2m7Jj_w4BAm9XIGMojJD-Wblf7-WKB1OWBDu9feYPxdzQag</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>817778205</pqid></control><display><type>article</type><title>Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections</title><source>Nature</source><creator>Hurdle, Julian G ; O'Neill, Alex J ; Chopra, Ian ; Lee, Richard E</creator><creatorcontrib>Hurdle, Julian G ; O'Neill, Alex J ; Chopra, Ian ; Lee, Richard E</creatorcontrib><description>Key Points
When bacteria become quiescent (that is, slow growing or non-growing), they can avoid being killed by bactericidal antibiotics. This phenomenon extends the period of morbidity experienced by the patient and necessitates prolonged antibiotic treatment to achieve a cure.
The effects of such bacteria are evident from several infections that typically contain these organisms, such as biofilm diseases, osteomyeletis and tuberculosis granuloma.
In the first decade of the new millenium, the discovery and development of antibiotics that target the function of the membrane have provided new paradigms with which to combat persisting bacteria.
In one approach, agents disorganize the structure and function of the membrane bilayer, causing subsequent multiple antibacterial effects in cells. Many of these membrane-active agents are reported to kill bacterial biofilms.
Moreover, agents that inhibit the function of bacterial respiratory and redox enzymes, thereby causing membrane depolarization and energy depletion, have been shown to kill dormant
Mycobacterium tuberculosis
.
The effects of membrane-active agents on quiescent cell types arise from the fact that all living bacteria require an intact, functional membrane and all living cells require energy to sustain their viability, even without growth.
Our understanding of slow-growing or non-growing bacteria has improved, as well as our knowledge about the mechanisms of membrane-acting agents. There are many opportunities for obtaining new classes of drugs based on our current understanding of the mechanisms behind these antimicrobials, as well as many challenges.
Infections involving slow-growing and persistent bacteria, including
Mycobacterium tuberculosis
and biofilms, are difficult to treat. Here, Hurdle and colleagues argue that developing antibiotics to target the bacterial membrane and membrane functions is a promising approach for the treatment for these difficult-to-treat infections.
Persistent infections involving slow-growing or non-growing bacteria are hard to treat with antibiotics that target biosynthetic processes in growing cells. Consequently, there is a need for antimicrobials that can treat infections containing dormant bacteria. In this Review, we discuss the emerging concept that disrupting the bacterial membrane bilayer or proteins that are integral to membrane function (including membrane potential and energy metabolism) in dormant bacteria is a strategy for treating persistent infections. The clinical applicability of these approaches is exemplified by the efficacy of lipoglycopeptides that damage bacterial membranes and of the diarylquinoline TMC207, which inhibits membrane-bound ATP synthase. Despite some drawbacks, membrane-active agents form an important new means of eradicating recalcitrant, non-growing bacteria.</description><identifier>ISSN: 1740-1526</identifier><identifier>EISSN: 1740-1534</identifier><identifier>DOI: 10.1038/nrmicro2474</identifier><identifier>PMID: 21164535</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/326/22/1290 ; 631/326/41/2531 ; 631/92/436/2388 ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - therapeutic use ; Antibiotics ; Antimicrobial agents ; Asymptomatic ; ATP ; Bacteria ; Bacteria - cytology ; Bacteria - drug effects ; Bacterial infections ; Bacterial Infections - drug therapy ; Biofilms ; Biology ; Biomedical and Life Sciences ; Biosynthesis ; Cell Membrane - drug effects ; Cell Membrane - physiology ; Cell membranes ; Cystic fibrosis ; Disease ; Drug resistance ; Drug Resistance, Bacterial ; Drug therapy ; Endocarditis ; Gene Expression Regulation, Bacterial - drug effects ; Health aspects ; Infections ; Infectious Diseases ; Life Sciences ; Medical equipment ; Medical Microbiology ; Membranes ; Metabolism ; Microbiology ; Parasitology ; Physiological aspects ; review-article ; Tuberculosis ; Virology</subject><ispartof>Nature reviews. Microbiology, 2011-01, Vol.9 (1), p.62-75</ispartof><rights>Springer Nature Limited 2011</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c635t-fdd2452ea818ab622dd7ae6b8e488b509ea1d62158521e2f9c07251e355fcf393</citedby><cites>FETCH-LOGICAL-c635t-fdd2452ea818ab622dd7ae6b8e488b509ea1d62158521e2f9c07251e355fcf393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,783,787,888,2736,27938,27939</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21164535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hurdle, Julian G</creatorcontrib><creatorcontrib>O'Neill, Alex J</creatorcontrib><creatorcontrib>Chopra, Ian</creatorcontrib><creatorcontrib>Lee, Richard E</creatorcontrib><title>Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections</title><title>Nature reviews. Microbiology</title><addtitle>Nat Rev Microbiol</addtitle><addtitle>Nat Rev Microbiol</addtitle><description>Key Points
When bacteria become quiescent (that is, slow growing or non-growing), they can avoid being killed by bactericidal antibiotics. This phenomenon extends the period of morbidity experienced by the patient and necessitates prolonged antibiotic treatment to achieve a cure.
The effects of such bacteria are evident from several infections that typically contain these organisms, such as biofilm diseases, osteomyeletis and tuberculosis granuloma.
In the first decade of the new millenium, the discovery and development of antibiotics that target the function of the membrane have provided new paradigms with which to combat persisting bacteria.
In one approach, agents disorganize the structure and function of the membrane bilayer, causing subsequent multiple antibacterial effects in cells. Many of these membrane-active agents are reported to kill bacterial biofilms.
Moreover, agents that inhibit the function of bacterial respiratory and redox enzymes, thereby causing membrane depolarization and energy depletion, have been shown to kill dormant
Mycobacterium tuberculosis
.
The effects of membrane-active agents on quiescent cell types arise from the fact that all living bacteria require an intact, functional membrane and all living cells require energy to sustain their viability, even without growth.
Our understanding of slow-growing or non-growing bacteria has improved, as well as our knowledge about the mechanisms of membrane-acting agents. There are many opportunities for obtaining new classes of drugs based on our current understanding of the mechanisms behind these antimicrobials, as well as many challenges.
Infections involving slow-growing and persistent bacteria, including
Mycobacterium tuberculosis
and biofilms, are difficult to treat. Here, Hurdle and colleagues argue that developing antibiotics to target the bacterial membrane and membrane functions is a promising approach for the treatment for these difficult-to-treat infections.
Persistent infections involving slow-growing or non-growing bacteria are hard to treat with antibiotics that target biosynthetic processes in growing cells. Consequently, there is a need for antimicrobials that can treat infections containing dormant bacteria. In this Review, we discuss the emerging concept that disrupting the bacterial membrane bilayer or proteins that are integral to membrane function (including membrane potential and energy metabolism) in dormant bacteria is a strategy for treating persistent infections. The clinical applicability of these approaches is exemplified by the efficacy of lipoglycopeptides that damage bacterial membranes and of the diarylquinoline TMC207, which inhibits membrane-bound ATP synthase. Despite some drawbacks, membrane-active agents form an important new means of eradicating recalcitrant, non-growing bacteria.</description><subject>631/326/22/1290</subject><subject>631/326/41/2531</subject><subject>631/92/436/2388</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>Asymptomatic</subject><subject>ATP</subject><subject>Bacteria</subject><subject>Bacteria - cytology</subject><subject>Bacteria - drug effects</subject><subject>Bacterial infections</subject><subject>Bacterial Infections - drug therapy</subject><subject>Biofilms</subject><subject>Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Biosynthesis</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - physiology</subject><subject>Cell membranes</subject><subject>Cystic fibrosis</subject><subject>Disease</subject><subject>Drug resistance</subject><subject>Drug Resistance, Bacterial</subject><subject>Drug therapy</subject><subject>Endocarditis</subject><subject>Gene Expression Regulation, Bacterial - drug effects</subject><subject>Health aspects</subject><subject>Infections</subject><subject>Infectious Diseases</subject><subject>Life Sciences</subject><subject>Medical equipment</subject><subject>Medical Microbiology</subject><subject>Membranes</subject><subject>Metabolism</subject><subject>Microbiology</subject><subject>Parasitology</subject><subject>Physiological aspects</subject><subject>review-article</subject><subject>Tuberculosis</subject><subject>Virology</subject><issn>1740-1526</issn><issn>1740-1534</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNptks9vFSEQx4nR2Fo9eTdrPXjQVxdYWNaDSdP4K2nipZ4Jyw5bml14Amv0v3farc9X03CAMJ_5Mt9hCHlO6xNac_UupNnbFFnTNg_IIW2bekMFbx7uzkwekCc5X9U1E6Jlj8kBo1Q2gotDAhcmjVB8GKve2ALJm6maYe6TCVC5JdjiY3hfmVAtYYAEv7ZT9AUGhOylCT7PlYupKgnMjcoWUva5QCiVDw5u0vNT8siZKcOz2_2IfP_08eLsy-b82-evZ6fnGyu5KBs3DKwRDIyiyvSSsWFoDcheQaNUL-oODB0ko0IJRoG5ztYtExS4EM463vEj8mHV3S79DIPFKpKZ9Db52aTfOhqv70aCv9Rj_Kl500kmJQq8vhVI8ccCuejZZwvThN2IS9ZKdqLlQlEkj_8jr-KSArrTirZtq1gtEHq1QqOZQGM_Ir5qryX1KTrFirlUSJ3cQ-EaAH82BnAe7-8kvFkT8NtzTuB2Dmmtr2dC780E0i_2m7Jj_w4BAm9XIGMojJD-Wblf7-WKB1OWBDu9feYPxdzQag</recordid><startdate>20110101</startdate><enddate>20110101</enddate><creator>Hurdle, Julian G</creator><creator>O'Neill, Alex J</creator><creator>Chopra, Ian</creator><creator>Lee, Richard E</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7RV</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7T7</scope><scope>5PM</scope></search><sort><creationdate>20110101</creationdate><title>Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections</title><author>Hurdle, Julian G ; O'Neill, Alex J ; Chopra, Ian ; Lee, Richard E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c635t-fdd2452ea818ab622dd7ae6b8e488b509ea1d62158521e2f9c07251e355fcf393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/326/22/1290</topic><topic>631/326/41/2531</topic><topic>631/92/436/2388</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Antibiotics</topic><topic>Antimicrobial agents</topic><topic>Asymptomatic</topic><topic>ATP</topic><topic>Bacteria</topic><topic>Bacteria - cytology</topic><topic>Bacteria - drug effects</topic><topic>Bacterial infections</topic><topic>Bacterial Infections - drug therapy</topic><topic>Biofilms</topic><topic>Biology</topic><topic>Biomedical and Life Sciences</topic><topic>Biosynthesis</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - physiology</topic><topic>Cell membranes</topic><topic>Cystic fibrosis</topic><topic>Disease</topic><topic>Drug resistance</topic><topic>Drug Resistance, Bacterial</topic><topic>Drug therapy</topic><topic>Endocarditis</topic><topic>Gene Expression Regulation, Bacterial - drug effects</topic><topic>Health aspects</topic><topic>Infections</topic><topic>Infectious Diseases</topic><topic>Life Sciences</topic><topic>Medical equipment</topic><topic>Medical Microbiology</topic><topic>Membranes</topic><topic>Metabolism</topic><topic>Microbiology</topic><topic>Parasitology</topic><topic>Physiological aspects</topic><topic>review-article</topic><topic>Tuberculosis</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hurdle, Julian G</creatorcontrib><creatorcontrib>O'Neill, Alex J</creatorcontrib><creatorcontrib>Chopra, Ian</creatorcontrib><creatorcontrib>Lee, Richard E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature reviews. Microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hurdle, Julian G</au><au>O'Neill, Alex J</au><au>Chopra, Ian</au><au>Lee, Richard E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections</atitle><jtitle>Nature reviews. Microbiology</jtitle><stitle>Nat Rev Microbiol</stitle><addtitle>Nat Rev Microbiol</addtitle><date>2011-01-01</date><risdate>2011</risdate><volume>9</volume><issue>1</issue><spage>62</spage><epage>75</epage><pages>62-75</pages><issn>1740-1526</issn><eissn>1740-1534</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><abstract>Key Points
When bacteria become quiescent (that is, slow growing or non-growing), they can avoid being killed by bactericidal antibiotics. This phenomenon extends the period of morbidity experienced by the patient and necessitates prolonged antibiotic treatment to achieve a cure.
The effects of such bacteria are evident from several infections that typically contain these organisms, such as biofilm diseases, osteomyeletis and tuberculosis granuloma.
In the first decade of the new millenium, the discovery and development of antibiotics that target the function of the membrane have provided new paradigms with which to combat persisting bacteria.
In one approach, agents disorganize the structure and function of the membrane bilayer, causing subsequent multiple antibacterial effects in cells. Many of these membrane-active agents are reported to kill bacterial biofilms.
Moreover, agents that inhibit the function of bacterial respiratory and redox enzymes, thereby causing membrane depolarization and energy depletion, have been shown to kill dormant
Mycobacterium tuberculosis
.
The effects of membrane-active agents on quiescent cell types arise from the fact that all living bacteria require an intact, functional membrane and all living cells require energy to sustain their viability, even without growth.
Our understanding of slow-growing or non-growing bacteria has improved, as well as our knowledge about the mechanisms of membrane-acting agents. There are many opportunities for obtaining new classes of drugs based on our current understanding of the mechanisms behind these antimicrobials, as well as many challenges.
Infections involving slow-growing and persistent bacteria, including
Mycobacterium tuberculosis
and biofilms, are difficult to treat. Here, Hurdle and colleagues argue that developing antibiotics to target the bacterial membrane and membrane functions is a promising approach for the treatment for these difficult-to-treat infections.
Persistent infections involving slow-growing or non-growing bacteria are hard to treat with antibiotics that target biosynthetic processes in growing cells. Consequently, there is a need for antimicrobials that can treat infections containing dormant bacteria. In this Review, we discuss the emerging concept that disrupting the bacterial membrane bilayer or proteins that are integral to membrane function (including membrane potential and energy metabolism) in dormant bacteria is a strategy for treating persistent infections. The clinical applicability of these approaches is exemplified by the efficacy of lipoglycopeptides that damage bacterial membranes and of the diarylquinoline TMC207, which inhibits membrane-bound ATP synthase. Despite some drawbacks, membrane-active agents form an important new means of eradicating recalcitrant, non-growing bacteria.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21164535</pmid><doi>10.1038/nrmicro2474</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1740-1526 |
| ispartof | Nature reviews. Microbiology, 2011-01, Vol.9 (1), p.62-75 |
| issn | 1740-1526 1740-1534 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3496266 |
| source | Nature |
| subjects | 631/326/22/1290 631/326/41/2531 631/92/436/2388 Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use Antibiotics Antimicrobial agents Asymptomatic ATP Bacteria Bacteria - cytology Bacteria - drug effects Bacterial infections Bacterial Infections - drug therapy Biofilms Biology Biomedical and Life Sciences Biosynthesis Cell Membrane - drug effects Cell Membrane - physiology Cell membranes Cystic fibrosis Disease Drug resistance Drug Resistance, Bacterial Drug therapy Endocarditis Gene Expression Regulation, Bacterial - drug effects Health aspects Infections Infectious Diseases Life Sciences Medical equipment Medical Microbiology Membranes Metabolism Microbiology Parasitology Physiological aspects review-article Tuberculosis Virology |
| title | Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-11-02T19%3A31%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Targeting%20bacterial%20membrane%20function:%20an%20underexploited%20mechanism%20for%20treating%20persistent%20infections&rft.jtitle=Nature%20reviews.%20Microbiology&rft.au=Hurdle,%20Julian%20G&rft.date=2011-01-01&rft.volume=9&rft.issue=1&rft.spage=62&rft.epage=75&rft.pages=62-75&rft.issn=1740-1526&rft.eissn=1740-1534&rft_id=info:doi/10.1038/nrmicro2474&rft_dat=%3Cgale_pubme%3EA245393368%3C/gale_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c635t-fdd2452ea818ab622dd7ae6b8e488b509ea1d62158521e2f9c07251e355fcf393%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=817778205&rft_id=info:pmid/21164535&rft_galeid=A245393368&rfr_iscdi=true |