Retained Activity of an O25b-Specific Monoclonal Antibody against an Mcr-1-Producing Escherichia coli Sequence Type 131 Strain

Guachalla, Luis Miguel; Ramoni, Katharina; Varga, Cecília; Mutti, Michele; Ghazawi, Akela; Pál, Tibor; Nagy, Eszter; Sonnevend, Ágnes; Nagy, Gábor; Szijártó, Valéria

doi:10.1128/aac.00046-18

Cited by 8 publications

(13 citation statements)

References 11 publications

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“…This includes humanized monoclonal antibodies that have been previously shown to target the LPS O25b antigen that is associated with E. coli ST131-H30 182 . The expression of mcr-1 does not affect the binding of ASn-4 to the LPS's O-antigen and the integration of the complement membrane-attack complex (MAC) into the LPS-modified outer membrane 182 . This means the expression of mcr-1 in E. coli ST131-H30 does not affect the functionality of the human immune system, nor does it not aid the strain via immune evasion.…”

Section: Dobias Et Al (2017)mentioning

confidence: 99%

Global Epidemiology and Genetic Environment of mcr genes: A One Health Systematic Review of Current and Emerging Trends

Mmatli

Mbelle

Sekyere

2022

Preprint

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Background: Mobile colistin resistance (mcr) genes modify Lipid A molecules of the lipopolysaccharide, changing the overall charge of the outer membrane. Methods: A systematic review of all studies published between January 2015 to July 2021 was performed. Included articles described mcr genes in the context of their genetic environment, fitness cost, crystal structure, their enzymatic activity and the risk factors associated with the acquisition of mcr. Studies describing the epidemiology of mcr genes and novel therapeutics were included.Results and Discussion: Ten mcr genes have been described to date within eleven Enterobacteriaceae species, with Escherichia coli, Klebsiella pneumoniae, and Salmonella species being the most predominant. They are present worldwide in 72 countries, with human specimens currently having the highest incidence. This is due to the wide dissemination of mcr in livestock animals, meat, manure, the environment, and wastewater samples, increasing the risk of transmission via foodborne, zoonotic, and vector-borne routes to humans. The stability and spread of mcr genes were mediated by mobile genetic elements such as the IncHI2 conjugative plasmid, which is associated with multiple mcr-variants and other antibiotic resistance genes. The cost of acquiring mcr is reduced by compensatory adaptation mechanisms. MCR proteins are well conserved via structurally. Hence, MCR-1 inhibitors and therapeutics should be applicable to all MCR proteins.Conclusion: Mcr genes have spread from animals into the clinical setting, threatening public health. Combination therapies are a promising option for managing and treating colistin-resistant Enterobacteriaceae isolates whilst reducing the toxic effects of colistin.

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Section: Dobias Et Al (2017)mentioning

confidence: 99%

Global Epidemiology and Genetic Environment of mcr genes: A One Health Systematic Review of Current and Emerging Trends

Mmatli

Mbelle

Sekyere

2022

Preprint

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“…It had been demonstrated that O25b-specific MAb ASN-4 retained its bactericidal activity against an MCR-1 -positive colistin-resistant ST131-H30 strain by three mechanisms of action that are opsonophagocytosis, endotoxin neutralization, and complement-mediated killing. Subsequently, LPS O-antigen-targeting antibodies are thought to be an alternative way of combating MDR infections, including the emerging MCR-1 -positive isolates [ 198 ]. The general mode of action of novel antibodies against bacteria is depicted in Figure 8 .…”

Section: Novel Antibodies Against Mdr Bacteriamentioning

confidence: 99%

Pulling the Brakes on Fast and Furious Multiple Drug-Resistant (MDR) Bacteria

Khan

Manzoor

Sultan

et al. 2021

IJMS

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Life-threatening bacterial infections have been managed by antibiotics for years and have significantly improved the wellbeing and lifetime of humans. However, bacteria have always been one step ahead by inactivating the antimicrobial agent chemically or by producing certain enzymes. The alarming universal occurrence of multidrug-resistant (MDR) bacteria has compelled researchers to find alternative treatments for MDR infections. This is a menace where conventional chemotherapies are no longer promising, but several novel approaches could help. Our current review article discusses the novel approaches that can combat MDR bacteria: starting off with potential nanoparticles (NPs) that efficiently interact with microorganisms causing fatal changes in the morphology and structure of these cells; nanophotothermal therapy using inorganic NPs like AuNPs to destroy pathogenic bacterial cells; bacteriophage therapy against which bacteria develop less resistance; combination drugs that act on dissimilar targets in distinctive pathways; probiotics therapy by the secretion of antibacterial chemicals; blockage of quorum sensing signals stopping bacterial colonization, and vaccination against resistant bacterial strains along with virulence factors. All these techniques show us a promising future in the fight against MDR bacteria, which remains the greatest challenge in public health care.

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“…Moreover mAbs offer advantages in terms of limitation of selective pressure and precise delivery through engineering [ 116 ]. Nonetheless, there is only one mAb (A1124) currently proposed to treat multidrug resistant ExPEC sequence type 131-H30 [ 117 ], whose activity was confirmed against a colistin-resistant strain [ 118 ]. Its specific action on the LPS O-antigen (O25b) of E. coli points out the importance of saccharide epitopes to elicit protective mAbs [ 119 ].…”

Section: State Of the Art Of Vaccines And Mabs To Tackle Pseudomonas Aeruginosa And Escherichia Colimentioning

confidence: 99%

Strategies to Tackle Antimicrobial Resistance: The Example of Escherichia coli and Pseudomonas aeruginosa

Antonelli

Cappelli

Cinelli

et al. 2021

IJMS

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Traditional antimicrobial treatments consist of drugs which target different essential functions in pathogens. Nevertheless, bacteria continue to evolve new mechanisms to evade this drug-mediated killing with surprising speed on the deployment of each new drug and antibiotic worldwide, a phenomenon called antimicrobial resistance (AMR). Nowadays, AMR represents a critical health threat, for which new medical interventions are urgently needed. By 2050, it is estimated that the leading cause of death will be through untreatable AMR pathogens. Although antibiotics remain a first-line treatment, non-antibiotic therapies such as prophylactic vaccines and therapeutic monoclonal antibodies (mAbs) are increasingly interesting alternatives to limit the spread of such antibiotic resistant microorganisms. For the discovery of new vaccines and mAbs, the search for effective antigens that are able to raise protective immune responses is a challenging undertaking. In this context, outer membrane vesicles (OMV) represent a promising approach, as they recapitulate the complete antigen repertoire that occurs on the surface of Gram-negative bacteria. In this review, we present Escherichia coli and Pseudomonas aeruginosa as specific examples of key AMR threats caused by Gram-negative bacteria and we discuss the current status of mAbs and vaccine approaches under development as well as how knowledge on OMV could benefit antigen discovery strategies.

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Retained Activity of an O25b-Specific Monoclonal Antibody against an Mcr-1-Producing Escherichia coli Sequence Type 131 Strain

Cited by 8 publications

References 11 publications

Global Epidemiology and Genetic Environment of mcr genes: A One Health Systematic Review of Current and Emerging Trends

Global Epidemiology and Genetic Environment of mcr genes: A One Health Systematic Review of Current and Emerging Trends

Pulling the Brakes on Fast and Furious Multiple Drug-Resistant (MDR) Bacteria

Strategies to Tackle Antimicrobial Resistance: The Example of Escherichia coli and Pseudomonas aeruginosa

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