The Remarkable Innate Resistance of Burkholderia bacteria to Cationic Antimicrobial Peptides: Insights into the Mechanism of AMP Resistance

Ghimire, Jenisha; Guha, Shantanu; Nelson, Benjamin; Morici, Lisa A.; Wimley, William C

doi:10.1007/s00232-022-00232-2

Cited by 8 publications

(7 citation statements)

References 75 publications

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“…In the condition of innate resistance such that pseudomonas aeruginosa relate to alteration in the outer membrane lipopolysaccharide (OM-LPS). In this case, membrane permeability is too much low and a primary cause of innate resistance toward many antibiotics 10 . Acquired resistance is brought about by mutation in chromosome or accession of transposon or plasmid that harbors determined for resistance 7 .…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial efficacy of Mentha piperata-derived biogenic zinc oxide nanoparticles against UTI-resistant pathogens

Ahmad,

Ali,

Abbas

et al. 2023

Sci Rep

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Misuse of antibiotics leads to the worldwide spread of antibiotic resistance, which motivates scientists to create new antibiotics. The recurring UTI due to antibiotics-resistant microorganism’s challenges scientists globally. The biogenic nanoparticles have the potential to meet the escalating requirements of novel antimicrobial agents. The green synthesis of nanoparticles (NPs) gained more attention due to their reliable applications against resistant microbes. The current study evaluates the biogenic ZnO NPs of Mentha piperata extract against resistant pathogens of urinary tract infections by agar well diffusion assay. The biogenic ZnO NPs revealed comparatively maximum inhibition in comparison to synthetic antibiotics against two bacterial strains (Proteus mirabilis, Pseudomonas aeruginosa) and a fungal strain (Candida albicans).The synthesized biogenic ZnO NPs alone revealed maximum activities than the combination of plant extract (PE) and ZnO NPs, and PE alone. The physiochemical features of ZnO NPs characterized through UV–Vis spectroscopy, FTIR, XRD, SEM, and EDX. The UV–Vis spectroscopy revealed 281.85 nm wavelengths; the XRD pattern revealed the crystalline structure of ZnO NPs. The FTIR analysis revealed the presence of carboxylic and nitro groups, which could be attributed to plant extract. SEM analysis revealed spherical hollow symmetry due to electrostatic forces. The analysis via EDX confirmed the presence of Zn and oxygen in the sample. The physiochemical features of synthesized ZnO NPs provide pivotal information such as quality and effectiveness. The current study revealed excellent dose-dependent antimicrobial activity against the pathogenic isolates from UTI-resistant patients. The higher concentration of ZnONPs interacts with the cell membrane which triggers oxidative burst. They may bind with the enzymes and proteins and brings epigenetic alteration which leads to membrane disruption or cell death.

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Section: Introductionmentioning

confidence: 99%

Antimicrobial efficacy of Mentha piperata-derived biogenic zinc oxide nanoparticles against UTI-resistant pathogens

Ahmad,

Ali,

Abbas

et al. 2023

Sci Rep

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“…However, a much bigger gain-of-function was observed when we compared their activities against clinical isolates of drug-resistant bacteria, with a focus on K. pneumoniae, a species of Gram-negative bacteria of rising concern that can show innate resistance to AMPs. − Two independent sets of isolates were tested, as described in the Methods section.…”

Section: Resultsmentioning

confidence: 99%

Optimization of Host Cell-Compatible, Antimicrobial Peptides Effective against Biofilms and Clinical Isolates of Drug-Resistant Bacteria

et al. 2023

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Here, we describe the continued synthetic molecular evolution of a lineage of host-compatible antimicrobial peptides (AMP) intended for the treatment of wounds infected with drug-resistant, biofilm-forming bacteria. The peptides tested are variants of an evolved AMP called d-amino acid CONsensus with Glycine Absent (d-CONGA), which has excellent antimicrobial activities in vitro and in vivo. In this newest generation of rational d-CONGA variants, we tested multiple sequence–structure–function hypotheses that had not been tested in previous generations. Many of the peptide variants have lower antibacterial activity against Gram-positive or Gram-negative pathogens, especially variants that have altered hydrophobicity, secondary structure potential, or spatial distribution of charged and hydrophobic residues. Thus, d-CONGA is generally well tuned for antimicrobial activity. However, we identified a variant, d-CONGA-Q7, with a polar glutamine inserted into the middle of the sequence, that has higher activity against both planktonic and biofilm-forming bacteria as well as lower cytotoxicity against human fibroblasts. Against clinical isolates of Klebsiella pneumoniae, innate resistance to d-CONGA was surprisingly common despite a lack of inducible resistance in Pseudomonas aeruginosa reported previously. Yet, these same isolates were susceptible to d-CONGA-Q7. d-CONGA-Q7 is much less vulnerable to AMP resistance in Gram-negative bacteria than its predecessor. Consistent with the spirit of synthetic molecular evolution, d-CONGA-Q7 achieved a critical gain-of-function and has a significantly better activity profile.

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“…3. However, a much bigger gain-of-function was observed when we compared their activities against clinical isolates of drug-resistant bacteria, with a focus on K. pneumoniae, a species of Gram-negative bacteria of rising concern that can show innate resistance to AMPs [16][17][18] . Two independent sets of isolates were tested, as described in Methods, below.…”

Section: Activity Against Clinical Isolates Of Gram-negative Pathogensmentioning

confidence: 99%

Optimization of host cell-compatible, antimicrobial peptides effective against biofilms and clinical isolates of drug-resistant bacteria

Ghimire

Hart

Soldano

et al. 2022

Preprint

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Here, we describe the synthetic molecular evolution of a family of host-compatible antimicrobial peptides (AMP) designed for the treatment of wounds infected with drug-resistant, biofilm forming bacteria. The peptides tested are variants of an evolved AMP called D-CONGA, which has excellent antimicrobial activities in vitro and in vivo. In this generation of rational D-CONGA variants, we tested multiple sequence-function hypotheses that had not been tested in previous generations. Many of the peptide variants tested have lower antibacterial activity against Gram-positive and Gram-negative pathogens, especially those that have altered hydrophobicity, secondary structure potential, or spatial distribution of charged and hydrophobic residues. Thus, D-CONGA is generally well tuned for good antimicrobial activity. However, we identified one variant, D-CONGA-Q7, with a polar glutamine inserted into the middle of the sequence, that has higher activity against both planktonic and biofilm-forming bacteria and lower cytotoxicity against human fibroblasts. Against clinical isolates of K. pneumoniae, innate resistance to D-CONGA was surprisingly common despite a lack of inducible resistance in P. aeruginosa reported in our previous work. Yet, these same isolates are susceptible to D-CONGA-Q7. Additional mechanistic work will be required to understand why D-CONGA-Q7 is less prone to innate resistance in Gram-negative bacteria. In the spirit of synthetic molecular evolution, the discovery of D-CONGA-Q7 achieved a critical gain-of-function, and has provided a significantly better template sequence for the next generation of synthetic evolution.

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The Remarkable Innate Resistance of Burkholderia bacteria to Cationic Antimicrobial Peptides: Insights into the Mechanism of AMP Resistance

Cited by 8 publications

References 75 publications

Antimicrobial efficacy of Mentha piperata-derived biogenic zinc oxide nanoparticles against UTI-resistant pathogens

Antimicrobial efficacy of Mentha piperata-derived biogenic zinc oxide nanoparticles against UTI-resistant pathogens

Optimization of Host Cell-Compatible, Antimicrobial Peptides Effective against Biofilms and Clinical Isolates of Drug-Resistant Bacteria

Optimization of host cell-compatible, antimicrobial peptides effective against biofilms and clinical isolates of drug-resistant bacteria

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