Emergence of polymyxin resistance in Gram-negative bacteria

Olaitan, Abiola Olumuyiwa; Li, Jian

doi:10.1016/j.ijantimicag.2016.11.003

Cited by 22 publications

(19 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MCRPEC was first discovered on the premise that E. coli can rarely acquire colistin resistance by chromosomal mutations alone and that the levels mediated by mcr-1 are moderate compared with other mechanisms 1 , 2 , 9 . Data previously published by us would suggest that the level of in vivo colistin resistance mediated by MCRPEC can protect the cells compared to control strains 9 .…”

Section: Resultsmentioning

confidence: 99%

“…The global concern over colistin resistance has profound implications as to how we successfully manage and treat serious Gram-negative infections, particularly those caused by Enterobacteriaceae 1 , 2 . Until recently, our understanding of colistin resistance was limited to chromosomal changes such as the pmrA/pmrB activation of arnBCADTEF and pmrE , that collectively modifies lipopolysaccharide (LPS), the component of the Gram-negative outer membrane by the addition of 4-amino-4-deoxy- l -arabinose 3 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms

et al. 2017

View full text Add to dashboard Cite

MCR-1 is a lipid A modifying enzyme that confers resistance to the antibiotic colistin. Here, we analyse the impact of MCR-1 expression on E. coli morphology, fitness, competitiveness, immune stimulation and virulence. Increased expression of mcr-1 results in decreased growth rate, cell viability, competitive ability and significant degradation in cell membrane and cytoplasmic structures, compared to expression of catalytically inactive MCR-1 (E246A) or MCR-1 soluble component. Lipopolysaccharide (LPS) extracted from mcr-1 strains induces lower production of IL-6 and TNF, when compared to control LPS. Compared to their parent strains, high-level colistin resistance mutants (HLCRMs) show reduced fitness (relative fitness is 0.41–0.78) and highly attenuated virulence in a Galleria mellonella infection model. Furthermore, HLCRMs are more susceptible to most antibiotics than their respective parent strains. Our results show that the bacterium is challenged to find a delicate equilibrium between expression of MCR-1-mediated colistin resistance and minimalizing toxicity and thus ensuring cell survival.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms

et al. 2017

View full text Add to dashboard Cite

show abstract

“…coding for a two-component system associated with colistin resistance, were identified in 39 (26.7%) and 55 (37.7%) isolates, respectively ( Figure 1). [27][28][29][30][31][32] The mutations were mostly localized in two (G53 and R81) and five (L10, C84, P94, E121 and A159) amino acid hot spots in PmrA and PmrB, respectively (Figure 3 and Table S4); these positions were shown to be critical for colistin resistance. 1 All except one of these mutations (strain 806A) were predicted as impacting the protein (Table S4).…”

Section: Prevalence and Characteristics Of Mcr-positive Strainsmentioning

confidence: 99%

Colistin resistance in Parisian inpatient faecal Escherichia coli as the result of two distinct evolutionary pathways

Bourrel

Poirel

Royer

et al. 2019

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

Background: Beyond plasmid-encoded resistance (mcr genes) prevalence in strain collections, large epidemiological studies to estimate the human burden of colistin-resistant Escherichia coli gut carriage are lacking. Objectives: To evaluate the prevalence of colistin-resistant E. coli carriage in inpatients and decipher the molecular support of resistance and the genetic background of the strains. Methods: During a 3 month period in 2017, we prospectively screened patients in six Parisian hospitals for rectal carriage of colistin-resistant E. coli using a selective medium, a biochemical confirmatory test and MIC determination. WGS of the resistant strains and their corresponding plasmids was performed. Results: Among the 1217 screened patients, 153 colistin-resistant E. coli strains were isolated from 152 patients (12.5%). The mcr-1 gene was identified in only seven isolates (4.6%) on different plasmid scaffolds. The genetic background of these MCR-1 producers argued for an animal origin. Conversely, the remaining 146 colistinresistant E. coli exhibited a phylogenetic distribution corresponding to human gut commensal/clinical population structure (B2 and D phylogroup predominance); 72.6% of those isolates harboured convergent mutations in the PmrA and PmrB proteins, constituting a two-component system shown to be associated with colistin resistance. Conclusions: We showed that the occurrence at a high rate of colistin resistance in human faecal E. coli is the result of two distinct evolutionary pathways, i.e. the occurrence of chromosomal mutations in an endogenous E. coli population and the rare acquisition of exogenous mcr-1-bearing strains probably of animal origin. The involved selective pressures need to be identified in order to develop preventative strategies.

show abstract

“…Polymyxin E (colistin) and polymyxin B are polycationic antimicrobial peptides that are considered as the last-line antibiotic treatment for multi-drug resistant (MDR) Gram-negative bacterial infections (Olaitan and Li, 2016 ). From the 1960s until the 1990s, colistin was considered as an effective treatment for MDR-GNB (Olaitan et al, 2014b ).…”

Section: Distribution Of Esbls and Ampc Producers In Animalsmentioning

confidence: 99%

“…From the 1960s until the 1990s, colistin was considered as an effective treatment for MDR-GNB (Olaitan et al, 2014b ). However, due its nephrotoxicity within the human body, the clinical use of this antimicrobial was abandoned (Olaitan and Li, 2016 ). Recently, the emergence of carbapenem resistance in clinically important bacteria such as P. aeruginosa, A. baumannii, K. pneumonia , and Escherichia coli , necessitated the re-introduction of colistin into clinical practice as a last-resort treatment option (Olaitan and Li, 2016 ).…”

Section: Distribution Of Esbls and Ampc Producers In Animalsmentioning

confidence: 99%

Prevalence and Emergence of Extended-Spectrum Cephalosporin-, Carbapenem- and Colistin-Resistant Gram Negative Bacteria of Animal Origin in the Mediterranean Basin

et al. 2018

View full text Add to dashboard Cite

In recent years, extended ESBL and carbapenemase producing Gram negative bacteria have become widespread in hospitals, community settings and the environment. This has been triggered by the few therapeutic options left when infections with these multi-drug resistant organisms occur. The emergence of resistance to colistin, the last therapeutic option against carbapenem-resistant bacteria, worsened the situation. Recently, animals were regarded as potent antimicrobial reservoir and a possible source of infection to humans. Enteric Gram negative bacteria in animals can be easily transmitted to humans by direct contact or indirectly through the handling and consumption of undercooked/uncooked animal products. In the Mediterranean basin, little is known about the current overall epidemiology of multi-drug resistant bacteria in livestock, companion, and domestic animals. This review describes the current epidemiology of ESBL, carbapenemase producers and colistin resistant bacteria of animal origin in this region of the world. The CTX-M group 1 seems to prevail in animals in this area, followed by SHV-12 and CTX-M group 9. The dissemination of carbapenemase producers and colistin resistance remains low. Isolated multi-drug resistant bacteria were often co-resistant to non-beta-lactam antibiotics, frequently used in veterinary medicine as treatment, growth promoters, prophylaxis and in human medicine for therapeutic purposes. Antibiotics used in veterinary medicine in this area include mainly tetracycline, aminoglycosides, fluoroquinolones, and polymyxins. Indeed, it appears that the emergence of ESBL and carbapenemase producers in animals is not related to the use of beta-lactam antibiotics but is, rather, due to the co-selective pressure applied by the over usage of non-beta-lactams. The level of antibiotic consumption in animals should be, therefore, re-considered in the Mediterranean area especially in North Africa and western Asia where no accurate data are available about the level of antibiotic consumption in animals.

show abstract

Emergence of polymyxin resistance in Gram-negative bacteria

Cited by 22 publications

References 12 publications

Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms

Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms

Colistin resistance in Parisian inpatient faecal Escherichia coli as the result of two distinct evolutionary pathways

Prevalence and Emergence of Extended-Spectrum Cephalosporin-, Carbapenem- and Colistin-Resistant Gram Negative Bacteria of Animal Origin in the Mediterranean Basin

Contact Info

Product

Resources

About