Plasmid-mediated resistance
Plasmid-mediated resistance is the transfer of
Properties of resistance plasmids
Resistance plasmids by definition carry one or more antibiotic resistance genes.
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, transposons, and ISCR-promoted gene mobilization.[7]
Most of the resistance plasmids are conjugative, meaning that they encode all the needed components for the transfer of the plasmid to another bacterium,[11] and that isn't present in mobilizable plasmids. According to that, Mobilizable plasmids are smaller in size (usually < 10 kb) while conjugative plasmids are largger (usually > 30 kb) due to the considerable size of DNA required to encode the conjugation mechanisms that allow for cell-to-cell conjugation.[7]
R-factor
R-factors are also called a resistance factors or resistance plasmid. They are tiny, circular DNA elements that are self-replicating,
Structure of Resistance Plasmids
The majority of the R-RTF (Resistance Transfer Factor) molecules are found in the resistance plasmid, which can be conceptualized as a circular piece of DNA with a length of 80 to 95 kb.[12] This plasmid shares many genes with the F factor and is largely homologous to it.[17] Additionally, it has a fin 0 gene that inhibits the transfer operon's functionality. The size and number of drug resistance genes in each R factor varies.The RTF is bigger than the R determinant. An IS 1 element separates the RTF and R determinant on either side before they combine into a single unit.The IS 1 components simplify it for R determinants to be transferred between different R-RTF unit types.[12]
Functions of Resistance Plasmids
- they play a role in the autonomous replication, conjugation, and ampicillin resistance genes.[12]
- Genes in the resistance plasmids enable bacteria to produce Pilli and develop resistance to antibiotics.[7]
- MDR genes in bacteria are transmitted mainly through the resistance plasmids.[4]
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,[18] and eventually triggers the formation of a mating bridge, merging the cytoplasms of two bacteria via a controlled pore.[19] 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.[20] Since many R-factors contain F-plasmids, antibiotic resistance can be easily spread among a population of bacteria.[21] Also, R-factors can be taken up by "DNA pumps" in their membranes via transformation,[22] or less commonly through viral mediated transduction,[23] or via bacteriophage, although conjugation is the most common means of antibiotic resistance spread. They contain the gene called RTF (Resistance transfer factor).
Enterobacteriaceae
it is a family of Gram-negative rod-shaped (bacilli) bacteria, the pathogenic bacteria that are most frequently found in the environment and clinical cases, as a result, they are significantly impacted by the use of antibiotics in agriculture, the ecosystem, or the treatment of diseases.[24] In Enterobacteriaceae, 28 different plasmid types can be identified by PCR-based replicon typing (PBRT).The plasmids that have been frequently reported [IncF, IncI, IncA/C, IncL (previously designated IncL/M), IncN, and IncH] contain a broad variety of resistance genes.[25]
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.[5]
Beta-lactam resistance
B-lactamases are antibiotic-hydrolyzing enzymes that typically cause resistance to b-lactam antibiotics. These enzymes are prevalent in Streptomyces, and together with related enzymes discovered in pathogenic and non-pathogenic bacteria, they form the protein family known as the "b-lactamase superfamily".[14] it is hypothesized that b-lactamases also serve a double purpose, such as housekeeping and antibiotic resistance.[26]
Both narrow spectrum beta-lactamases (e.g. penicillinases) and
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.[5]
In addition, since the plasmids that carry ESBL genes also commonly encode
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.[5]
Quinolone resistance
Several studies have shown that fluoroquinolone resistance has enhanced worldwide, especially in Enterobacteriaceae members. QnrA was the first known plasmid-mediated gene associated in quinolone resistance.[28]Quinolone resistance genes are frequently located on the same plasmid as the ESBL genes.[29] The proteins known as QnrS, QnrB, QnrC, and QnrD are four others that are similar. Numerous variants have been found for qnrA, qnrS, and qnrB, and they are distinguished by sequential numbers.[30] The qnr genes can be discovered in integrons and transposons on MDR plasmids of various incompatibility groups, which could carry a number of resistance-related molecules, such as carbapenemases and ESBLs.[31] 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.[5]
Aminoglycoside resistance
xResistance to aminoglycosides in Gram-negative pathogens is primarily caused by enzymes that acetylate, adenylate, or phosphorylate the medication.[32] On mobile elements, such as plasmids, are the genes that encode these enzymes.[33]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.[5] Resistance to aminoglycosides is conferred via numerous mechanisms:
- aminoglycoside-modifying enzymes and inactivation of the aminoglycosides, which is frequently seen in both gram-positive and gram-negative bacteria and is induced by nucleotidyltransferases, phosphotransferases, or aminoglycoside acetyltransferases.
- reduced permeability.
- enhanced efflux.
- variations to the 30S ribosomal subunit that prevent aminoglycosides from binding to it.[34]
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.[35]
References
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- ^ Sevim A, Sevim E (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.
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- ^ a b c d e f "R-Factor - Structure and Functions of Resistance Factors or Plasmids". BYJUS. Retrieved 11 January 2023.
- ^ "R-Factor". VEDANTU. Retrieved 8 January 2023.
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- ^ "Prokaryotic Cell Structure: Pili". Archived from the original on 7 December 2016. Retrieved 19 January 2017.
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- ^ Dahal P (20 May 2022). "Enterobacteriaceae- Definition, Characteristics, Identification". Microbe Notes. Retrieved 9 January 2023.
- PMID 29370371.
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- ^ Hussain T, Jamal M, Nighat F, Andleeb S (2014). "Broad spectrum antibiotics and resistance in non-target bacteria: an example from tetracycline". Journal of Pure and Applied Microbiology. 8 (4): 2667–2671.
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Further reading
- Strahilevitz J, Jacoby GA, Hooper DC, Robicsek A (October 2009). "Plasmid-mediated quinolone resistance: a multifaceted threat". Clinical Microbiology Reviews. 22 (4): 664–689. PMID 19822894.
- Nordmann P, Poirel L (September 2005). "Emergence of plasmid-mediated resistance to quinolones in Enterobacteriaceae". The Journal of Antimicrobial Chemotherapy. 56 (3): 463–469. PMID 16020539.
- Oktem IM, Gulay Z, Bicmen M, Gur D (January 2008). "qnrA prevalence in extended-spectrum beta-lactamase-positive Enterobacteriaceae isolates from Turkey". Japanese Journal of Infectious Diseases. 61 (1): 13–17. S2CID 24744915.
- Chen LP, Cai XW, Wang XR, Zhou XL, Wu DF, Xu XJ, Chen HC (October 2010). "Characterization of plasmid-mediated lincosamide resistance in a field isolate of Haemophilus parasuis". The Journal of Antimicrobial Chemotherapy. 65 (10): 2256–2258. PMID 20699244.