Postantibiotic effect and postantibiotic sub-MIC effect of LTX-109 and mupirocin on <i>Staphylococcus aureus</i>
 blood isolates

Saravolatz, Louis D.; Pawlak, Joan; Martin, Hayley; Saravolatz, Stephanie; Johnson, Leonard B.; Wold, Hedda; Husbyn, Mette; Olsen, Wenche Marie

doi:10.1111/lam.12792

Cited by 18 publications

(18 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is one of the characteristics of pharmacodynamics being increasingly applied to the design of dosing regimens of antimicrobial agents. The inhibition in growth of the pathogen is followed by recovery and regain of their infectious potential, once the efficacy of antimicrobial agent was finished/reduced ( Saravolatz et al, 2017 ). Figure 1 suggested that S. aureus growth was delayed post 2 and 4 h treatment at two different concentrations of peptide-Ba49.…”

Section: Resultsmentioning

confidence: 99%

“…This suggested that the damage to the cell could be immense and might take a long time to repair. In comparison, a naturally produced AMP DLP4 from hemolymph of Hermetia illucens has been reported to have a PAE value of 8.83 h against S. aureus ( Li et al, 2020 ), and also a synthetic AMP, LTX-109, was shown to have 5.51 h of PAE against S. aureus ( Saravolatz et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Deciphering the Antibacterial Role of Peptide From Bacillus subtilis subsp. spizizenii Ba49 Against Staphylococcus aureus

et al. 2021

View full text Add to dashboard Cite

An increase in antibiotic resistance has led to escalating the need for the development of alternate therapy. Antimicrobial peptides (AMPs) are at the forefront of replacing conventional antibiotics, showing slower development of drug resistance, antibiofilm activity, and the ability to modulate the host immune response. The ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens that jeopardize most conventional antibiotics are known to be involved in severe respiratory tract, bloodstream, urinary tract, soft tissue, and skin infections. Among them, S. aureus is an insidious microbe and developed resistance against conventional antibiotics. In the present study, an AMP (named as peptide-Ba49) isolated from Bacillus subtilis subsp. spizizenii strain from Allium cepa (the common onion) exhibited strong antibacterial efficacy against S. aureus ATCC 25923. The mode of action of this peptide-Ba49 on S. aureus was deciphered through various sensitive probes, i.e., DiSC3 (5) and H2DCFDA, suggesting the peptide-Ba49 to be acting upon through change in membrane potential and by triggering the production of reactive oxygen species (ROS). This induced disruption of the cell membrane was further supported by morphological studies using scanning electron microscopy (SEM). Investigations on a possible post-antibiotic effect (PAE) of peptide-Ba49 showed prolonged PAE against S. aureus. Furthermore, the peptide-Ba49 prevented the formation of S. aureus biofilm at low concentration and showed its potential to degrade the mature biofilm of S. aureus. The peptide-Ba49 also exhibited intracellular killing potential against S. aureus ATCC 25923 in the macrophage cells, and moreover, peptide-Ba49 was found to bolster the fibroblast cell migration in the scratch assay at low concentration, exhibiting a wound healing efficacy of this peptide. These studies demonstrated that peptide-Ba49 isolated from the strain B. subtilis subsp. spizizenii could be a therapeutic candidate to combat the pathogenic S. aureus infections.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Deciphering the Antibacterial Role of Peptide From Bacillus subtilis subsp. spizizenii Ba49 Against Staphylococcus aureus

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Probably, the so called "post-antibiotic sub-MIC effect" (PA-SME) is the phenomenon most closely related to PAEP. In contrast to PAEP, which involves two different agents, PA-SME results in sensitization to an antibiotic at subinhibitory concentrations after exposure to the same compound at concentrations above its MIC [47][48][49][50][51][52]. Similarly, increased bacterial susceptibility to phagocytosis or intracellular killing by leukocytes during the PAE phase was described by McDonald and collaborators, which defined this phenomenon as Post-antibiotic Leukocyte Enhancement (PALE) [53].…”

Section: Discussionmentioning

confidence: 99%

A synthetic peptide sensitizes multi-drug resistant Pseudomonas aeruginosa to antibiotics for more than two hours and permeabilizes its envelope for twenty hours

2020

View full text Add to dashboard Cite

Background: Pseudomonas aeruginosa is a Gram-negative pathogen that frequently causes life-threatening infections in immunocompromised patients. We previously showed that subinhibitory concentrations of short synthetic peptides permeabilize P. aeruginosa and enhance the lethal action of co-administered antibiotics. Methods: Long-term permeabilization caused by exposure of multidrug-resistant P. aeruginosa strains to peptide P4-9 was investigated by measuring the uptake of several antibiotics and fluorescent probes and by using confocal imaging and atomic force microscopy. Results: We demonstrated that P4-9, a 13-amino acid peptide, induces a growth delay (i.e. post-antibiotic effect) of 1.3 h on a multidrug-resistant P. aeruginosa clinical isolate. Remarkably, when an independently P4-9-treated culture was allowed to grow in the absence of the peptide, cells remained sensitive to subinhibitory concentrations of antibiotics such as ceftazidime, fosfomycin and erythromycin for at least 2 h. We designated this persistent sensitization to antibiotics occurring in the absence of the sensitizing agent as Post-Antibiotic Effect associated Permeabilization (PAEP). Using atomic force microscopy, we showed that exposure to P4-9 induces profound alterations on the bacterial surface and that treated cells need at least 2 h of growth to repair those lesions. During PAEP, P. aeruginosa mutants overexpressing either the efflux pump MexAB-OprM system or the AmpC β-lactamase were rendered sensitive to antibiotics that are known substrates of those mechanisms of resistance. Finally, we showed for the first time that the descendants of bacteria surviving exposure to a membrane disturbing peptide retain a significant level of permeability to hydrophobic compounds, including propidium iodide, even after 20 h of growth in the absence of the peptide. Conclusions: The phenomenon of long-term sensitization to antibiotics shown here may have important therapeutic implications for a combined peptide-antibiotic treatment because the peptide would not need to be present to exert its antibiotic enhancing activity as long as the target organism retains sensitization to the antibiotic.

show abstract

“…LTX-109 (LTX109, Lytixar, LTX 109) is an AMP peptidomimetic (Arg-Tbt-Arg-NH-EtPh) that was in clinical development by Lytix Biopharma AS. LTX-109 contains 2 arginine residues, a central modified tryptophan residue (2,5,7-tri( tert -butyl)tryptophan) and an ethylphenyl group at the C-terminus ( 242 ) with antibacterial ( 243 , 244 ) and antifungal activity ( 245 ). LTX-109 was fungicidal against S. cerevisiae (MIC 8 mg/L), causing a 3 log kill within 60 min, and was also active against pre-formed S. cerevisiae biofilms.…”

Section: Novel Antifungal Peptides In Clinical and Preclinical Develomentioning

confidence: 99%

Innate Inspiration: Antifungal Peptides and Other Immunotherapeutics From the Host Immune Response

Mercer

O’Neil

2020

Front. Immunol.

View full text Add to dashboard Cite

The purpose of this review is to describe antifungal therapeutic candidates in preclinical and clinical development derived from, or directly influenced by, the immune system, with a specific focus on antimicrobial peptides (AMP). Although the focus of this review is AMP with direct antimicrobial effects on fungi, we will also discuss compounds with direct antifungal activity, including monoclonal antibodies (mAb), as well as immunomodulatory molecules that can enhance the immune response to fungal infection, including immunomodulatory AMP, vaccines, checkpoint inhibitors, interferon and colony stimulating factors as well as immune cell therapies. The focus of this manuscript will be a non-exhaustive review of antifungal compounds in preclinical and clinical development that are based on the principles of immunology and the authors acknowledge the incredible amount of in vitro and in vivo work that has been conducted to develop such therapeutic candidates.

show abstract

Postantibiotic effect and postantibiotic sub-MIC effect of LTX-109 and mupirocin on Staphylococcus aureus blood isolates

Cited by 18 publications

References 9 publications

Deciphering the Antibacterial Role of Peptide From Bacillus subtilis subsp. spizizenii Ba49 Against Staphylococcus aureus

Deciphering the Antibacterial Role of Peptide From Bacillus subtilis subsp. spizizenii Ba49 Against Staphylococcus aureus

A synthetic peptide sensitizes multi-drug resistant Pseudomonas aeruginosa to antibiotics for more than two hours and permeabilizes its envelope for twenty hours

Innate Inspiration: Antifungal Peptides and Other Immunotherapeutics From the Host Immune Response

Contact Info

Product

Resources

About