A d-octapeptide drug efflux pump inhibitor acts synergistically with azoles in a murine oral candidiasis infection model

Hayama, Koremasa; Ishibashi, Hidetoshi; Ishijima, Sanae A.; Niimi, Kyoko; Tansho, Shigeru; Ono, Yasuo; Monk, Brian C.; Holmes, Ann R.; Harding, D. R.; Cannon, Richard D.; Abe, Shigeru

doi:10.1111/j.1574-6968.2011.02490.x

Cited by 32 publications

(29 citation statements)

References 25 publications

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“…The inhibitors for ABC pumps such as milbemycins, enniatin, FK506, FK520, and unnarmicins can be used along with azole drugs to reverse the drug resistance [73, 156–159]. Recently, Hayama et al have assessed the therapeutic potential of D-octapeptide derivative RC21v3 (an inhibitor of Cdr1p) in a murine oral candidiasis infection model and have shown its potential in combination with fluconazole [160]. This suggests that this inhibitor has a potential in treating oral candidiasis.…”

Section: Discussionmentioning

confidence: 99%

CandidaInfections and Their Prevention

Kabir

Ahmad

2013

ISRN Preventive Medicine

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Infections caused by Candida species have been increased dramatically worldwide due to the increase in immunocompromised patients. For the prevention and cure of candidiasis, several strategies have been adopted at clinical level. Candida infected patients are commonly treated with a variety of antifungal drugs such as fluconazole, amphotericin B, nystatin, and flucytosine. Moreover, early detection and speciation of the fungal agents will play a crucial role for administering appropriate drugs for antifungal therapy. Many modern technologies like MALDI-TOF-MS, real-time PCR, and DNA microarray are being applied for accurate and fast detection of the strains. However, during prolonged use of these drugs, many fungal pathogens become resistant and antifungal therapy suffers. In this regard, combination of two or more antifungal drugs is thought to be an alternative to counter the rising drug resistance. Also, many inhibitors of efflux pumps have been designed and tested in different models to effectively treat candidiasis. However, most of the synthetic drugs have side effects and biomedicines like antibodies and polysaccharide-peptide conjugates could be better alternatives and safe options to prevent and cure the diseases. Furthermore, availability of genome sequences of Candida albicans and other non-albicans strains has made it feasible to analyze the genes for their roles in adherence, penetration, and establishment of diseases. Understanding the biology of Candida species by applying different modern and advanced technology will definitely help us in preventing and curing the diseases caused by fungal pathogens.

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Section: Discussionmentioning

confidence: 99%

CandidaInfections and Their Prevention

Kabir

Ahmad

2013

ISRN Preventive Medicine

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“…Although predisposing factors, such as xerostomia and estrogen administration, have been used for inducing oral candidiasis in mice, most studies have been performed in immunosuppressed mice models 37 , 41 , 43 , 62 - 68 . Takakura et al 37 developed a murine model for experimental candidiasis that combines immunosuppression and treatment with tetracycline for successful disease progression, allowing the study of fungal pathogenesis and new therapeutic options.…”

Section: Models Of Experimental Oral Candidiasis In Micementioning

confidence: 99%

Recent mouse and rat methods for the study of experimental oral candidiasis

et al. 2013

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The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis.

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“…Using a mouse model of lethal infection, it was demonstrated that concomitant administration of the lactoferricin-derived peptide P2-15 and erythromycin against P. aeruginosa afforded long-lasting protection to one-third of the animals [180]. A d-octapeptide EPI acts synergistically with azoles in a murine oral candidiasis infection model [181]. In a latest in vivo study, PDT employing EPIs was able to reduce bacterial load in P. aeruginosa burn wounds, to delay bacteremia and to keep the bacterial levels in blood 2-3 log 10 lower compared to an untreated group [182].…”

Section: Introductionmentioning

confidence: 99%

Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation

Kourtesi¹,

Ball²,

Huang³

et al. 2013

TOMICROJ

136

103

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Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches.

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A d-octapeptide drug efflux pump inhibitor acts synergistically with azoles in a murine oral candidiasis infection model

Cited by 32 publications

References 25 publications

CandidaInfections and Their Prevention

CandidaInfections and Their Prevention

Recent mouse and rat methods for the study of experimental oral candidiasis

Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation

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