Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity

Xing, Yu-hua; Wang, Wei; Dai, Su-qin; Liu, Ti-yan; Tan, Jacqueline; Qu, Guolong; Li, Yuxia; Yan, Lei; Liu, Gang; Fu, Xueqi; Chen, Huipeng

doi:10.1038/aps.2013.159

Cited by 20 publications

(19 citation statements)

References 28 publications

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“…At this concentration, relatively rapid (2-5 min) efflux of potassium and influx of sodium ions were observed. However, potassium efflux was only 60% of the release measured with the carrier ionophore valinomycin [58]. In B. subtilis, ATP leakage experiments showed that it takes 5× MIC and treatment times of 60-120 min to achieve about 80% loss of intracellular ATP [76].…”

Section: Pore Formation In Vivomentioning

confidence: 97%

“…A later study used different lipid mixtures, including 3:1 DMPC/DMPG and 1:1 POPC/POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol), and found that daptomycin pores are likely selective for potassium ions [55]. In fact, some studies have observed potassium leakage from bacterial cells [56][57][58]. Several studies supported the model of a more or less organized daptomycin pore.…”

Section: Mechanism Of Action In Model Membranesmentioning

confidence: 99%

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More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

Gray

Wenzel

2020

Antibiotics

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Daptomycin is a cyclic lipopeptide antibiotic, which was discovered in 1987 and entered the market in 2003. To date, it serves as last resort antibiotic to treat complicated skin infections, bacteremia, and right-sided endocarditis caused by Gram-positive pathogens, most prominently methicillin-resistant Staphylococcus aureus. Daptomycin was the last representative of a novel antibiotic class that was introduced to the clinic. It is also one of the few membrane-active compounds that can be applied systemically. While membrane-active antibiotics have long been limited to topical applications and were generally excluded from systemic drug development, they promise slower resistance development than many classical drugs that target single proteins. The success of daptomycin together with the emergence of more and more multi-resistant superbugs attracted renewed interest in this compound class. Studying daptomycin as a pioneering systemic membrane-active compound might help to pave the way for future membrane-targeting antibiotics. However, more than 30 years after its discovery, the exact mechanism of action of daptomycin is still debated. In particular, there is a prominent discrepancy between in vivo and in vitro studies. In this review, we discuss the current knowledge on the mechanism of daptomycin against Gram-positive bacteria and try to offer explanations for these conflicting observations.

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Section: Pore Formation In Vivomentioning

confidence: 97%

Section: Mechanism Of Action In Model Membranesmentioning

confidence: 99%

More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

Gray

Wenzel

2020

Antibiotics

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“…This agent binds to the bacterial membrane depolarizing the membrane potential resulting in DNA, RNA and protein synthesis inhibition ultimately leading to cell death [95–97]. This unique mechanism of action sets daptomycin apart from other antibiotic classes and to date, no resistant isolates have been documented.…”

Section: Antibiotics Currently Approved For the Treatment Of Other Bamentioning

confidence: 99%

Alternative pre-approved and novel therapies for the treatment of anthrax

2016

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Background Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient’s chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies.MethodsA literature search was conducted using the University of Manitoba search engine. Using this search engine allowed access to a greater variety of journals/articles that would have otherwise been restricted for general use. In order to be considered for discussion for this review, all articles must have been published later than 2009.ResultsThe alternative pre-approved antibiotics demonstrated high efficacy against B. anthracis both in vitro and in vivo. In addition, the safety profile and clinical pharmacology of these drugs were already known. Compounds that targeted underexploited bacterial processes (DNA replication, RNA synthesis, and cell division) were also very effective in combatting B. anthracis. In addition, these novel compounds prevented bacterial resistance. Targeting B. anthracis virulence, more specifically the anthrax toxins, increased the length of which treatment could be administered.ConclusionsSeveral novel and pre-existing antibiotics, as well as toxin inhibitors, have shown increasing promise. A combination treatment that targets both bacterial growth and toxin production would be ideal and probably necessary for effectively combatting this armed bacterium.

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“…It is wellestablished as an antibiotic since 2003, marketed as Cubicin Ò (Chan Tompkins and Harnicar 2008). Daptomycin has been successfully administered for skin infections, endocarditis, osteomyelitis, soft-tissue infections, even anthrax (Kaya et al 2013;Gould et al 2013;Xing et al 2014). …”

Section: Daptomycinmentioning

confidence: 99%

“…At an MIC value of 0.78 lg/ml, it eradicated the anthrax pathogen Bacillus anthracis AP422, by perturbing the latter's membrane potential. The efficacy was comparable to ciprofloxacin and penicillin G, though the mechanism of inhibition varied (Xing et al 2014). The calcium dependent attachment as well as insertion of the lipophilic part to pathogen's cytoplasm, followed by rapid potassium efflux leading to depolarization of the cell membrane has been understood (Silverman et al 2003;Beiras-Fernandez et al 2010).…”

Section: Antibacterialmentioning

confidence: 99%

Therapeutic cyclic lipopeptides mining from microbes: latest strides and hurdles

Patel

Ahmed

Eswari

2015

World J Microbiol Biotechnol

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Infectious diseases impose serious public health burdens and often have devastating consequences. The cyclic lipopeptides elaborated by bacteria Bacillus, Paenibacillus, Pseudomonas, Streptomyces, Serratia, Propionibacterium and fungus Fusarium are very crucial in restraining the pathogens. Composed of a peptide and a fatty acyl moiety these amphiphilic metabolites exhibit broad spectrum antimicrobial effects. Among the plethora of cyclic lipopeptides, only selective few have emerged as robust antibiotics. For their functional vigor, polymyxin, daptomycin, surfactin, iturin, fengysin, paenibacterin and pseudofactin have been integrated in mainstream healthcare. Daptomycin has been a significant part of antimicrobial arsenal since the past decade. As the magnitude of drug resistance rises in unprecedented manner, the urgency of prospecting novel cyclic lipopeptides is being perceived. Intense research has revealed the implication of these bioactive compounds stretching beyond antibacterial and antifungal. Anticancer, immunomodulatory, prosthetic parts disinfection and vaccine adjuvancy are some of the validated prospects. This review discusses the emerging applications, mechanisms governing the biological actions, role of genomics in refining structure and function, semi-synthetic analog discovery, novel strain isolation, setbacks etc. Though its beyond the scope of the current topic, for holistic purpose, the role of lipopeptides in bioremediation and crop biotechnology has been briefly outlined. This updated critique is expected to galvanize innovations and diversify therapeutic recruitment of microbial lipopeptides.

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Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity

Cited by 20 publications

References 28 publications

More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

Alternative pre-approved and novel therapies for the treatment of anthrax

Therapeutic cyclic lipopeptides mining from microbes: latest strides and hurdles

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