Broad-spectrum antimicrobial efficacy of peptide A3-APO in mouse models of multidrug-resistant wound and lung infections cannot be explained by in vitro activity against the pathogens involved

Ostorházi, Eszter; Holub, Marianna Csilla; Rozgonyi, Ferenc; Harmos, Ferenc; Cassone, Marco; Wade, John D.; Ötvös, László

doi:10.1016/j.ijantimicag.2011.01.003

Cited by 58 publications

(41 citation statements)

References 15 publications

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“…Bacterial counts of mice infected with 2 ϫ 10 11 CFU/ wound were in the range of 10 7 for control animals and below 10 3 for the majority of A3-APO-treated animals (47). Further studies revealed that the peptide reduced MRSA counts in burn wounds from 10 7 to 10 4 CFU/mg of tissue and increased survival of mice infected with a cocktail of A. baumanni, Klebsiella pneumoniae, and Proteus mirabilis (48).…”

Section: Discussionmentioning

confidence: 94%

Evaluation of a Nisin-Eluting Nanofiber Scaffold To Treat Staphylococcus aureus-Induced Skin Infections in Mice

Heunis

Smith

Dicks

2013

Antimicrob Agents Chemother

130

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Staphylococcus aureus is a virulent pathogen and a major causative agent of superficial and invasive skin and soft tissue infections (SSSTIs). Antibiotic resistance in S. aureus, among other bacterial pathogens, has rapidly increased, and this is placing an enormous burden on the health care sector and has serious implications for infected individuals, especially immunocompromised patients. Alternative treatments thus need to be explored to continue to successfully treat infections caused by S. aureus, including antibiotic-resistant strains of S. aureus. In this study, an antimicrobial nanofiber wound dressing was generated by electrospinning nisin (Nisaplin) into poly(ethylene oxide) and poly(D,L-lactide) (50:50) blend nanofibers. Active nisin diffused from the nanofiber wound dressings for at least 4 days in vitro, as shown by consecutive transfers onto plates seeded with strains of methicillin-resistant S. aureus (MRSA). The nisin-containing nanofiber wound dressings significantly reduced S. aureus Xen 36 bioluminescence in vivo and viable cell numbers in a murine excisional skin infection model. The bacterial burden of wounds treated with nisin-containing nanofiber wound dressings was 4.3 ؋ 10 2 CFU/wound, whereas wounds treated with control nanofiber wound dressings had 2.2 ؋ 10 7 CFU/wound on the last day of the trial (day 7). Furthermore, the wound dressings stimulated wound closure of excisional wounds, and no adverse effects were observed by histological analysis. Nisin-containing nanofiber wound dressings have the potential to treat S. aureus skin infections and to potentially accelerate wound healing of excisional wounds.

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Section: Discussionmentioning

confidence: 94%

Evaluation of a Nisin-Eluting Nanofiber Scaffold To Treat Staphylococcus aureus-Induced Skin Infections in Mice

Heunis

Smith

Dicks

2013

Antimicrob Agents Chemother

130

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“…Proline-rich AMPs (PrAMPs), which are produced by insects with typical lengths of 18 to 25 residues or in mammals with 40 to 60 residues, represent a promising class of antibiotics (3)(4)(5)(6). Besides native PrAMPs, either shortened versions [e.g., bactenecin Bac7(1-35)] or chemically optimized versions (e.g., apidaecin 1b analogs Api88 and Api137 or oncocins Onc18, Onc72, and Onc112) and those with artificial sequences (e.g., A3-APO and its single-chain version Chex1-Arg20) were shown to be highly efficient against Gramnegative and partially even against Gram-positive bacteria in several different murine infection models (5,(7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Influence of the yjiL-mdtM Gene Cluster on the Antibacterial Activity of Proline-Rich Antimicrobial Peptides Overcoming Escherichia coli Resistance Induced by the Missing SbmA Transporter System

Krizsan

Knappe

Hoffmann

2015

Antimicrob Agents Chemother

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In view of increasing health threats from multiresistant pathogens, antimicrobial peptides (AMPs) and, specifically, proline-rich AMPs (PrAMPs) have been investigated in animal models. PrAMPs enter bacteria via the ABC transporter SbmA and inhibit intracellular targets. We used phage transduction (Tn10 insertion) to screen by random mutagenesis for alternative uptake mechanisms for analogs of apidaecin 1b, a honeybee-derived PrAMP. All 24 apidaecin-resistant mutants had the Tn10 insertion in the sbmA gene. These sbmA::Tn10 insertion mutants and the Escherichia coli BW25113 ⌬sbmA (JW0368) strain were still susceptible to the bactenecin PrAMP Bac7(1-35) and oncocin PrAMPs Onc18 and Onc112, as well as to Chex1-Arg20, despite significantly reduced internalizations. In a second round of random mutagenesis, the remaining susceptibility was linked to the yjiLmdtM gene cluster. E. coli BW25113 and its ⌬yjiL null mutant (JW5785) were equally susceptible to all PrAMPs tested, whereas the BW25113 ⌬mdtM mutant was less susceptible to oncocins. The JW0368 yjiL::Tn10 transposon mutant (BS2) was resistant to all short PrAMPs and susceptible only to full-length Bac7 and A3-APO. Interestingly, PrAMPs appear to enter bacteria via MdtM, a multidrug resistance transporter (drug/H ؉ antiporter) of the major facilitator superfamily (MFS) that can efflux antibiotics, biocides, and bile salts. In conclusion, PrAMPs enter bacteria via ABC and MFS transporters that efflux antibiotics and cytotoxic compounds from the cytoplasm to the periplasm. There are rising death tolls due to drug-resistant bacteria among persons with weakened or suppressed immune systems. The worldwide spread of multiresistant or even extensively resistant bacteria has therefore triggered intense research efforts to identify novel antibiotic classes, especially those with new modes of action (1). In recent years, thousands of gene-encoded antimicrobial peptides (AMPs) have been identified in different organisms and investigated in vitro and often in vivo, with several being now pursued in preclinical studies (2, 3). Proline-rich AMPs (PrAMPs), which are produced by insects with typical lengths of 18 to 25 residues or in mammals with 40 to 60 residues, represent a promising class of antibiotics (3-6). Besides native PrAMPs, either shortened versions [e.g., bactenecin Bac7(1-35)] or chemically optimized versions (e.g., apidaecin 1b analogs Api88 and Api137 or oncocins Onc18, Onc72, and Onc112) and those with artificial sequences (e.g., A3-APO and its single-chain version Chex1-Arg20) were shown to be highly efficient against Gramnegative and partially even against Gram-positive bacteria in several different murine infection models (5, 7-12).PrAMPs appear to pass readily across the outer membrane of Gram-negative bacteria before they are actively transported into the cytoplasm by SbmA (13,14). This 406-residue-long integral inner membrane protein has common features with the ATPbinding cassette (ABC) transporters but lacks the nucleotide binding domain and requires an e...

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“…В Санкт-Петербургском университете уже разра-ботано несколько иммуномодулирующих и анти-микробных препаратов на основе ПБ-АМП насекомых [3]. В Европе также создается анти-бактериальный препарат на базе одного из пеп-тидов насекомых -А3-АРО [11]. Необходимость дальнейшего интенсивного изучения ПБ-АМП и разработки подобных препаратов в нашей стра-не не вызывает сомнений.…”

Section: Abstract: Innate Immunity Drug-resistant Bacteria Proline-unclassified

Effects of Proline-Rich Peptides of the Innate Immune System on Drug-Resistant Bacterial Strains

Zharkova¹,

Копейкин²,

Афиногенов³

et al. 2018

Med. immunol.

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Broad-spectrum antimicrobial efficacy of peptide A3-APO in mouse models of multidrug-resistant wound and lung infections cannot be explained by in vitro activity against the pathogens involved

Cited by 58 publications

References 15 publications

Evaluation of a Nisin-Eluting Nanofiber Scaffold To Treat Staphylococcus aureus-Induced Skin Infections in Mice

Evaluation of a Nisin-Eluting Nanofiber Scaffold To Treat Staphylococcus aureus-Induced Skin Infections in Mice

Influence of the yjiL-mdtM Gene Cluster on the Antibacterial Activity of Proline-Rich Antimicrobial Peptides Overcoming Escherichia coli Resistance Induced by the Missing SbmA Transporter System

Effects of Proline-Rich Peptides of the Innate Immune System on Drug-Resistant Bacterial Strains

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