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[[Image:Example plasmid.svg|right|thumb|200px|An example plasmid with two areas of [[antibiotic resistance]] coding [[DNA]] (1,2) and an [[origin of replication]] (3).]]
[[Image:Example plasmid.svg|right|thumb|200px|An example plasmid with two areas of [[antibiotic resistance]] coding [[DNA]] (1,2) and an [[origin of replication]] (3).]]
'''Plasmid-mediated resistance''' is the transfer of [[antibiotic resistance]] genes which are carried on [[plasmid]]s.<ref>{{cite journal | vauthors = San Millan A | title = Evolution of Plasmid-Mediated Antibiotic Resistance in the Clinical Context | journal = Trends in Microbiology | volume = 26 | issue = 12 | pages = 978–985 | date = December 2018 | pmid = 30049587 | doi = 10.1016/j.tim.2018.06.007 }}</ref> The plasmids can be transferred between [[bacteria]] within the same [[species]] or between different species via [[Bacterial conjugation|conjugation]].<ref>{{Cite web |title=conjugation (prokaryotes) {{!}} Learn Science at Scitable |url=https://www.nature.com/scitable/definition/conjugation-prokaryotes-290/ |access-date=2023-01-06 |website=www.nature.com |language=en}}</ref> Plasmids often carry multiple [[antibiotic resistance]] genes, contributing to the spread of [[Multidrug resistance|multidrug-resistance]] (MDR).<ref>{{cite journal | vauthors = Nikaido H | title = Multidrug resistance in bacteria | journal = Annual Review of Biochemistry | volume = 78 | issue = 1 | pages = 119–146 | date = 2009-06-01 | pmid = 19231985 | pmc = 2839888 | doi = 10.1146/annurev.biochem.78.082907.145923 }}</ref> Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by [[Gram-negative bacteria]], especially family [[Enterobacteriaceae]].<ref name=":0">{{cite journal | vauthors = Schultsz C, Geerlings S | title = Plasmid-mediated resistance in Enterobacteriaceae: changing landscape and implications for therapy | journal = Drugs | volume = 72 | issue = 1 | pages = 1–16 | date = January 2012 | pmid = 22191792 | doi = 10.2165/11597960-000000000-00000 | s2cid = 42306704 }}</ref> The global spread of MDR plasmids has been enhanced by [[selective pressure]] from antibiotic usage in human and [[veterinary medicine]].<ref>{{cite journal | vauthors = Carattoli A | title = Plasmid-mediated antimicrobial resistance in Salmonella enterica | journal = Current Issues in Molecular Biology | volume = 5 | issue = 4 | pages = 113–122 | date = October 2003 | pmid = 12921226 | url = http://www.horizonpress.com/cimb/v/v5/10.pdf }}</ref>
'''Plasmid-mediated resistance''' is the transfer of [[antibiotic resistance]] genes which are carried on [[plasmid]]s.<ref>{{cite journal | vauthors = San Millan A | title = Evolution of Plasmid-Mediated Antibiotic Resistance in the Clinical Context | journal = Trends in Microbiology | volume = 26 | issue = 12 | pages = 978–985 | date = December 2018 | pmid = 30049587 | doi = 10.1016/j.tim.2018.06.007 }}</ref> The plasmids can be transferred between [[bacteria]] within the same [[species]] or between different species via [[Bacterial conjugation|conjugation]].<ref>{{Cite web |title=conjugation (prokaryotes) {{!}} Learn Science at Scitable |url=https://www.nature.com/scitable/definition/conjugation-prokaryotes-290/ |access-date=2023-01-06 |website=www.nature.com |language=en}}</ref> Plasmids often carry multiple [[antibiotic resistance]] genes, contributing to the spread of [[Multidrug resistance|multidrug-resistance]] (MDR).<ref>{{cite journal | vauthors = Nikaido H | title = Multidrug resistance in bacteria | journal = Annual Review of Biochemistry | volume = 78 | issue = 1 | pages = 119–146 | date = 2009-06-01 | pmid = 19231985 | pmc = 2839888 | doi = 10.1146/annurev.biochem.78.082907.145923 }}</ref> Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by [[Gram-negative bacteria]], especially family [[Enterobacteriaceae]].<ref name=":0">{{cite journal | vauthors = Schultsz C, Geerlings S | title = Plasmid-mediated resistance in Enterobacteriaceae: changing landscape and implications for therapy | journal = Drugs | volume = 72 | issue = 1 | pages = 1–16 | date = January 2012 | pmid = 22191792 | doi = 10.2165/11597960-000000000-00000 | s2cid = 42306704 }}</ref> The global spread of MDR plasmids has been enhanced by [[selective pressure]] from antimicrobial medications used in medical facilities and when raising animals for food.<ref>{{Cite journal |last=Mathers |first=Amy J. |last2=Peirano |first2=Gisele |last3=Pitout |first3=Johann D. D. |date=2015 |title=The Role of Epidemic Resistance Plasmids and International High-Risk Clones in the Spread of Multidrug-Resistant Enterobacteriaceae |url=https://journals.asm.org/doi/10.1128/CMR.00116-14 |journal=Clinical Microbiology Reviews |language=en |volume=28 |issue=3 |pages=565–591 |doi=10.1128/CMR.00116-14 |issn=0893-8512 |pmc=PMC4405625 |pmid=25926236}}</ref>


== Properties of resistance plasmids ==
== Properties of resistance plasmids ==
Resistance plasmids by definition carry one or more antibiotic resistance genes. They are frequently accompanied by the genes encoding [[virulence]] determinants, specific enzymes or resistance to toxic [[heavy metals]]. Multiple resistance genes are commonly arranged in the resistance cassettes. The antibiotic resistance genes found on the plasmids confer resistance to most of the antibiotic classes used nowadays, for example, [[Β-lactam antibiotic|beta-lactams]], [[fluoroquinolones]] and [[aminoglycoside]]s.<ref name=":0" /><ref name=":1">{{cite journal | vauthors = Bennett PM | title = Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria | journal = British Journal of Pharmacology | volume = 153 | issue = Suppl 1 | pages = S347–S357 | date = March 2008 | pmid = 18193080 | pmc = 2268074 | doi = 10.1038/sj.bjp.0707607 }}</ref>
Resistance plasmids by definition carry one or more antibiotic resistance genes.<ref name=":2">{{Cite journal |last=Bennett |first=P M |date=2008 |title=Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria: Plasmid-encoded antibiotic resistance |url=http://doi.wiley.com/10.1038/sj.bjp.0707607 |journal=British Journal of Pharmacology |language=en |volume=153 |issue=S1 |pages=S347–S357 |doi=10.1038/sj.bjp.0707607 |pmc=PMC2268074 |pmid=18193080}}</ref> They are frequently accompanied by the genes encoding [[virulence]] determinants,<ref>{{Cite journal |last=Darmancier |first=Helena |last2=Domingues |first2=Célia P. F. |last3=Rebelo |first3=João S. |last4=Amaro |first4=Ana |last5=Dionísio |first5=Francisco |last6=Pothier |first6=Joël |last7=Serra |first7=Octávio |last8=Nogueira |first8=Teresa |date=2022 |title=Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids |url=https://www.mdpi.com/2079-6382/11/6/706 |journal=Antibiotics |language=en |volume=11 |issue=6 |pages=706 |doi=10.3390/antibiotics11060706 |issn=2079-6382}}</ref> specific enzymes or resistance to toxic [[heavy metals]].<ref>{{Cite journal |last=SEVİM, SEVİM |first=Ali, Elif |date=2015 |title=Plasmid Mediated Antibiotic and Heavy Metal Resistance in Bacillus Strains Isolated from Soils in Rize, Turkey |url=https://dergipark.org.tr/tr/download/article-file/194072 |journal=Suleyman Demirel University Journal of Natural and Applied Science |volume=19 |issue=2 |pages=133-141 |via=Süleyman Demirel University science Institute}}</ref> Multiple resistance genes are commonly arranged in the resistance cassettes.<ref name=":2" /> The antibiotic resistance genes found on the plasmids confer resistance to most of the antibiotic classes used nowadays, for example, [[Β-lactam antibiotic|beta-lactams]], [[fluoroquinolones]] and [[aminoglycoside]]s.<ref>{{Cite journal |last=McMillan |first=Elizabeth A. |last2=Gupta |first2=Sushim K. |last3=Williams |first3=Laura E. |last4=Jové |first4=Thomas |last5=Hiott |first5=Lari M. |last6=Woodley |first6=Tiffanie A. |last7=Barrett |first7=John B. |last8=Jackson |first8=Charlene R. |last9=Wasilenko |first9=Jamie L. |last10=Simmons |first10=Mustafa |last11=Tillman |first11=Glenn E. |last12=McClelland |first12=Michael |last13=Frye |first13=Jonathan G. |date=2019 |title=Antimicrobial Resistance Genes, Cassettes, and Plasmids Present in Salmonella enterica Associated With United States Food Animals |url=https://www.frontiersin.org/articles/10.3389/fmicb.2019.00832 |journal=Frontiers in Microbiology |volume=10 |doi=10.3389/fmicb.2019.00832/full |issn=1664-302X}}</ref>


It is very common for the resistance genes or entire resistance cassettes to be re-arranged on the same plasmid or be moved to a different plasmid or chromosome by means of recombination systems. Examples of such systems include [[integron]]s and [[Transposable element|transposons]].<ref name=":1" />
It is very common for the resistance genes or entire resistance cassettes to be re-arranged on the same plasmid or be moved to a different plasmid or chromosome by means of recombination systems. Examples of such systems include [[integron]]s and [[Transposable element|transposons]].<ref name=":1">{{cite journal |vauthors=Bennett PM |date=March 2008 |title=Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria |journal=British Journal of Pharmacology |volume=153 |issue=Suppl 1 |pages=S347–S357 |doi=10.1038/sj.bjp.0707607 |pmc=2268074 |pmid=18193080}}</ref>


Most of the resistance plasmids are conjugative, meaning that they encode all the needed components for the transfer of the plasmid to other bacterium. Other smaller plasmids (usually < 10 kb in size) can be mobilized by a conjugative plasmid (usually > 30 kb) in order to be transferred.<ref name=":1" />
Most of the resistance plasmids are conjugative, meaning that they encode all the needed components for the transfer of the plasmid to other bacterium. Other smaller plasmids (usually < 10 kb in size) can be mobilized by a conjugative plasmid (usually > 30 kb) in order to be transferred.<ref name=":1" />

Revision as of 17:48, 7 January 2023

An example plasmid with two areas of antibiotic resistance coding DNA (1,2) and an origin of replication (3).

Plasmid-mediated resistance is the transfer of antibiotic resistance genes which are carried on plasmids.[1] The plasmids can be transferred between bacteria within the same species or between different species via conjugation.[2] Plasmids often carry multiple antibiotic resistance genes, contributing to the spread of multidrug-resistance (MDR).[3] Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by Gram-negative bacteria, especially family Enterobacteriaceae.[4] The global spread of MDR plasmids has been enhanced by selective pressure from antimicrobial medications used in medical facilities and when raising animals for food.[5]

Properties of resistance plasmids

Resistance plasmids by definition carry one or more antibiotic resistance genes.[6] They are frequently accompanied by the genes encoding virulence determinants,[7] specific enzymes or resistance to toxic heavy metals.[8] Multiple resistance genes are commonly arranged in the resistance cassettes.[6] The antibiotic resistance genes found on the plasmids confer resistance to most of the antibiotic classes used nowadays, for example, beta-lactams, fluoroquinolones and aminoglycosides.[9]

It is very common for the resistance genes or entire resistance cassettes to be re-arranged on the same plasmid or be moved to a different plasmid or chromosome by means of recombination systems. Examples of such systems include integrons and transposons.[10]

Most of the resistance plasmids are conjugative, meaning that they encode all the needed components for the transfer of the plasmid to other bacterium. Other smaller plasmids (usually < 10 kb in size) can be mobilized by a conjugative plasmid (usually > 30 kb) in order to be transferred.[10]

R-factor

This section is about the plasmid. For information about the residual factor in crystallography, see R-factor (crystallography). For the racing video game, see rFactor.

R-factors are pieces of DNA, usually plasmids, that contain antibiotic resistance genes. Resistance genes are ones that give rise to proteins that modify the antibiotic or pump it out. They are different from mutations that give bacteria resistance to antibiotics by preventing the antibiotic from getting in or changing the shape of the target protein. R-factors have been known to contain up to ten resistance genes. They can also spread easily as they contain genes for constructing pili, which allow them to transfer the R-factor to other bacteria. R-factors have contributed to the growing antibiotic resistance crisis because they quickly spread resistance genes amongst bacteria.[11]

Transmission

Bacteria containing F-factors (said to be "F+") have the capability for horizontal gene transfer; they can construct a sex pilus, which emerges from the donor bacterium and ensnares the recipient bacterium, draws it in, and eventually triggers the formation of a mating bridge, merging the cytoplasms of two bacteria via a controlled pore. This pore allows the transfer of genetic material, such as a plasmid. Conjugation allows two bacteria, not necessarily from the same species, to transfer genetic material one way.[12] Since many R-factors contain F-plasmids, antibiotic resistance can be easily spread among a population of bacteria. Also, R-factors can be taken up by "DNA pumps" in their membranes via transformation, or less commonly through viral mediated transduction, or via bacteriophage, although conjugation is the most common means of antibiotic resistance spread. They contain the gene called RTF (Resistance transfer factor).

Enterobacteriaceae

Escherichia coli bacteria on the right are sensitive to two beta-lactam antibiotics, and do not grow in the semi-circular regions surrounding the antibiotics. E. coli bacteria on the left are resistant to beta-lactam antibiotics, and grow next to one antibiotic (bottom) and are less inhibited by another antibiotic (top).

Members of family Enterobacteriaceae, for example, Escherichia coli or Klebsiella pneumoniae pose the biggest threat regarding plasmid-mediated resistance in hospital- and community-acquired infections.[4]

Beta-lactam resistance

Both narrow spectrum beta-lactamases (e.g. penicillinases) and extended spectrum beta-lactamases (ESBL) are common for resistance plasmids in Enterobacteriaceae. Often multiple beta-lactamase genes are found on the same plasmid hydrolyzing a wide spectrum of beta-lactam antibiotics.[4]

Extended spectrum beta-lactamases (ESBL)

ESBL enzymes can hydrolyze all beta-lactam antibiotics, including cephalosporins, except for the carpabepenems. The first clinically observed ESBL enzymes were mutated versions of the narrow spectrum beta-lactamases, like TEM and SHV. Other ESBL enzymes originate outside of family Enterobacteriaceae, but have been spreading as well.[4]

In addition, since the plasmids that carry ESBL genes also commonly encode resistance determinants for many other antibiotics, ESBL strains are often resistant to many non-beta-lactam antibiotics as well,[13] leaving very few options for the treatment.

Carbapenemases

Carbapenemases represent type of ESBL which are able to hydrolyze carbapenem antibiotics that are considered as the last-resort treatment for ESBL-producing bacteria. KPC, NDM-1, VIM and OXA-48 carbapenemases have been increasingly reported worldwide as causes of hospital-acquired infections.[4]

Quinolone resistance

Quinolone resistance genes are frequently located on the same plasmid as the ESBL genes. Examples of resistance mechanisms include different Qnr proteins, aminoglycose acetyltransferase aac(6')-Ib-cr that is able to hydrolyze ciprofloxacin and norfloxacin, as well as efflux transporters OqxAB and QepA.[4]

Aminoglycoside resistance

Aminoglycoside resistance genes are also commonly found together with ESBL genes. Resistance to aminoglycosides is conferred via numerous aminoglycoside-modifying enzymes and 16S rRNA methyltransferases.[4]

small RNAs

Study investigating physiological effect of pHK01 plasmid in host E.coli J53 found that the plasmid reduced bacterial motility and conferred resistance to beta-lactams. The pHK01 produced plasmid-encoded small RNAs and mediated expression of host sRNAs. These sRNAs were antisense to genes involved in replication, conjugate transfer and plasmid stabilisation : AS-repA3 (CopA), AS-traI, AS-finO, AS-traG, AS-pc02 . The over-expression of one of the plasmid-encoded antisense sRNAs: AS-traI shortened t lalog phase of host growth.[14]

References

  1. ^ San Millan A (December 2018). "Evolution of Plasmid-Mediated Antibiotic Resistance in the Clinical Context". Trends in Microbiology. 26 (12): 978–985. doi:10.1016/j.tim.2018.06.007. PMID 30049587.
  2. ^ "conjugation (prokaryotes) | Learn Science at Scitable". www.nature.com. Retrieved 6 January 2023.
  3. ^ Nikaido H (1 June 2009). "Multidrug resistance in bacteria". Annual Review of Biochemistry. 78 (1): 119–146. doi:10.1146/annurev.biochem.78.082907.145923. PMC 2839888. PMID 19231985.
  4. ^ a b c d e f g Schultsz C, Geerlings S (January 2012). "Plasmid-mediated resistance in Enterobacteriaceae: changing landscape and implications for therapy". Drugs. 72 (1): 1–16. doi:10.2165/11597960-000000000-00000. PMID 22191792. S2CID 42306704.
  5. ^ Mathers, Amy J.; Peirano, Gisele; Pitout, Johann D. D. (2015). "The Role of Epidemic Resistance Plasmids and International High-Risk Clones in the Spread of Multidrug-Resistant Enterobacteriaceae". Clinical Microbiology Reviews. 28 (3): 565–591. doi:10.1128/CMR.00116-14. ISSN 0893-8512. PMC 4405625. PMID 25926236.{{cite journal}}: CS1 maint: PMC format (link)
  6. ^ a b Bennett, P M (2008). "Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria: Plasmid-encoded antibiotic resistance". British Journal of Pharmacology. 153 (S1): S347–S357. doi:10.1038/sj.bjp.0707607. PMC 2268074. PMID 18193080.{{cite journal}}: CS1 maint: PMC format (link)
  7. ^ Darmancier, Helena; Domingues, Célia P. F.; Rebelo, João S.; Amaro, Ana; Dionísio, Francisco; Pothier, Joël; Serra, Octávio; Nogueira, Teresa (2022). "Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids". Antibiotics. 11 (6): 706. doi:10.3390/antibiotics11060706. ISSN 2079-6382.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ SEVİM, SEVİM, Ali, Elif (2015). "Plasmid Mediated Antibiotic and Heavy Metal Resistance in Bacillus Strains Isolated from Soils in Rize, Turkey". Suleyman Demirel University Journal of Natural and Applied Science. 19 (2): 133–141 – via Süleyman Demirel University science Institute.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ McMillan, Elizabeth A.; Gupta, Sushim K.; Williams, Laura E.; Jové, Thomas; Hiott, Lari M.; Woodley, Tiffanie A.; Barrett, John B.; Jackson, Charlene R.; Wasilenko, Jamie L.; Simmons, Mustafa; Tillman, Glenn E.; McClelland, Michael; Frye, Jonathan G. (2019). "Antimicrobial Resistance Genes, Cassettes, and Plasmids Present in Salmonella enterica Associated With United States Food Animals". Frontiers in Microbiology. 10. doi:10.3389/fmicb.2019.00832/full. ISSN 1664-302X.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ a b Bennett PM (March 2008). "Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria". British Journal of Pharmacology. 153 (Suppl 1): S347–S357. doi:10.1038/sj.bjp.0707607. PMC 2268074. PMID 18193080.
  11. ^ Campbell N (2018). Biology A Global Approach (11th ed.). New York: Pearson. p. 633. ISBN 978-1-292-17043-5.
  12. ^ "Prokaryotic Cell Structure: Pili". Archived from the original on 7 December 2016. Retrieved 19 January 2017.
  13. ^ Broad spectrum antibiotics and resistance in non-target bacteria: an example from tetracycline, Journal of Pure and Applied Microbiology, (2014); 8(4): 2667-2671.
  14. ^ Jiang X, Liu X, Law CO, Wang Y, Lo WU, Weng X, et al. (July 2017). "The CTX-M-14 plasmid pHK01 encodes novel small RNAs and influences host growth and motility". FEMS Microbiology Ecology. 93 (7). doi:10.1093/femsec/fix090. PMID 28854680.

Further reading


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