Mechanisms of Polymyxin Resistance

Moffatt, Jennifer H.; Harper, Marina; Boyce, John D.

doi:10.1007/978-3-030-16373-0_5

Cited by 154 publications

(149 citation statements)

References 96 publications

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“…Polymyxins are cationic amphipathic compounds, and initially interact with the negatively charged lipid A component of LPS. Controlled addition of positively charged residues such as PetNt to LPS reduces negative charge on bacterial surface and therefore limits interaction between the polymyxin and the LPS [208]. The expression of PetN transferases is regulated by the concerted action of TS systems [209].…”

Section: Polymyxinsmentioning

confidence: 99%

“…Lipid A modification by PetN transferase PmrC [208][209][210] MCR-1 [214] MCR-4 [215,216] Lack of lipid A biosynthesis LpxA, LpxC, or LpxD [211] Decreased stability of outer membrane LpsB, LptD, and VacJ [212] Reduced biotin synthesis LpsB [207,212,213] ESBLs = Extended-spectrum β-lactamase; PBP = Penicillin binding protein; RND = resistance-nodulation-division; MATE = multidrug and toxic compound extrusion; SMR = small multidrug resistance; PetN = phosphoethanolamine.…”

Section: Target Mutationmentioning

confidence: 99%

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Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

2020

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Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. Pathogenesis in A. baumannii infections is an outcome of multiple virulence factors, including porins, capsules, and cell wall lipopolysaccharide, enzymes, biofilm production, motility, and iron-acquisition systems, among others. Such virulence factors help the organism to resist stressful environmental conditions and enable development of severe infections. Parallel to increased prevalence of infections caused by A. baumannii, challenging and diverse resistance mechanisms in this pathogen are well recognized, with major classes of antibiotics becoming minimally effective. Through a wide array of antibiotic-hydrolyzing enzymes, efflux pump changes, impermeability, and antibiotic target mutations, A. baumannii models a unique ability to maintain a multidrug-resistant phenotype, further complicating treatment. Understanding mechanisms behind diseases, virulence, and resistance acquisition are central to infectious disease knowledge about A. baumannii. The aims of this review are to highlight infections and disease-producing factors in A. baumannii and to touch base on mechanisms of resistance to various antibiotic classes.

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Section: Polymyxinsmentioning

confidence: 99%

Section: Target Mutationmentioning

confidence: 99%

Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

2020

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“…Resistance to polymyxins is seen in some Gram-negative species, such as Neisseria meningitidis, Proteus mirabilis and Burkholderia spp. These bacteria change the lipopolysaccharide (LPS) structure, as polymyxins initially interact with the negatively charged lipid A component of LPS [45].…”

Section: Use In Agriculturementioning

confidence: 99%

Antibiotics Overuse and Bacterial Resistance

Saleem¹,

Deters²,

Bastide³

et al. 2019

Ann Microbiol Res

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Antibiotic usage has become very widespread, as they are used to treat so many infectious diseases today. Antimicrobial agents exert their actions via different mechanisms including blockage of cell wall synthesis, interference of protein and/ or nucleic acid synthesis, interruption of cell membrane structure, and inhibition of a metabolic pathway. The treatment of bacterial infections with antimicrobial agents has become more difficult due to the capability of bacteria to develop resistance to antibiotics. Erroneous diagnosing, misconceptions, and improper physician-patient dynamics have led to overuse of antibiotics and the emergence of drug-resistant bacteria. Bacterial colonies have been shown to confer advantageous genetic information with ease, which is cause for concern. This, in turn, leads to a heightened urgency to create new forms of treatment that are effective against a greater proportion of a given bacterial colony. Effective ways of decreasing resistance include better diagnostic techniques, proper education and assessments, optimization of antibiotics usage, drug synergism, vaccine implementation, global efforts to combat resistance, and development of new antimicrobial agents.

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“…The mechanism by which polymyxin kills gram‐negative pathogens relies on disrupting membrane permeability through polar and hydrophobic interactions. In these interactions, there is an electrostatic interaction between the positively charged residues of polymyxin and the negatively charged lipid A moiety of the lipopolysaccharide . With the emergence of multidrug‐ and pandrug‐resistant gram‐negative pathogens in the 1990s, especially carbapenem‐resistant Enterobacter , we have to reactivate polymyxin in the absence of new antibacterials …”

Section: Introductionmentioning

confidence: 99%

“…In these interactions, there is an electrostatic interaction between the positively charged residues of polymyxin and the negatively charged lipid A moiety of the lipopolysaccharide. 7,8 With the emergence of multidrug-and pandrug-resistant gram-negative pathogens in the 1990s, especially carbapenem-resistant Enterobacter, we have to reactivate polymyxin in the absence of new antibacterials. [9][10][11] Since the first discovery of the transferable colistin resistance gene mcr-1 in China, more than 40 countries and regions around the world have detected such resistance genes.…”

Section: Introductionmentioning

confidence: 99%

Isoalantolactone restores the sensitivity of gram‐negative Enterobacteriaceae carrying MCR‐1 to carbapenems

Lü

Sun

et al. 2020

J Cellular Molecular Medi

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Polymyxin B has been re‐applied to the clinic as the final choice for the treatment of multidrug‐resistant gram‐negative pathogenic infections, but the use of polymyxin B has been re‐assessed because of the emergence and spread of the plasmid‐mediated mcr‐1 gene. The purpose of this study was to search for an MCR inhibitor synergistically acting with polymyxin to treat the infection caused by this pathogen. In this study, we used the broth microdilution checkerboard method to evaluate the synergistic effect of isoalantolactone (IAL) and polymyxin B on mcr‐1‐positive Enterobacteriaceae. Growth curve analysis, time‐killing assays and a combined disc test were used to further verify the efficacy of the combined drug. Colonization of the thigh muscle in mice, survival experiments and lung tissue section observations was used to determine the effect of synergy in vivo after Klebsiella pneumoniae and Escherichia coli infection. We screened a natural compound, IAL, which can enhance the sensitivity of polymyxin B to mcr‐1‐positive Enterobacteriaceae. The results showed that the combined use of polymyxin B and IAL has a synergistic effect on mcr‐1‐positive Enterobacteriaceae, such as K pneumoniae and E coli, not only in vitro but also in vivo. Our results indicate that IAL is a natural compound with broad application prospects that can prolong the service life of polymyxin B and make outstanding contributions to the treatment of gram‐negative Enterobacteriaceae infections resistant to polymyxin B.

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Mechanisms of Polymyxin Resistance

Cited by 154 publications

References 96 publications

Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

Antibiotics Overuse and Bacterial Resistance

Isoalantolactone restores the sensitivity of gram‐negative Enterobacteriaceae carrying MCR‐1 to carbapenems

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