Plasma Membrane Proteolipid 3 Protein Modulates Amphotericin B Resistance throughSphingolipid Biosynthetic Pathway

Bari, Vinay Kumar; Sharma, Sushma; Alfatah,; Mondal, Alok K.; Ganesan, K.

doi:10.1038/srep09685

Cited by 35 publications

(23 citation statements)

References 55 publications

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“…It has been shown to have good stability to both pH and temperature and to be included in the secondary metabolism and considered an accessory enzyme in the nonribosomal peptides production . Recently, Bari et al assumed that plasma membrane proteolipid 3 protein through sphingolipid biosynthetic pathway modulates amphotericin B resistance. Plasma membrane proteolipid 3 was found in M. canis .…”

Section: Discussionmentioning

confidence: 99%

Towards a rapid identification and a novel proteomic analysis for dermatophytes from human and animal dermatophytosis

Tartor

Hashem

Enany

2019

Mycoses

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Summary Background Since accurate identification of dermatophyte species is essential for epidemiological studies and implementing antifungal treatment, overcoming limitations of conventional diagnostics is a fruitful subject. Objectives and methods In this study, we investigated real‐time polymerase chain reaction(q‐PCR), matrix‐assisted laser desorption/ionisation time of flight mass spectrometry (MALDI‐TOF MS) and nano‐electrospray ionisation mass spectrometry (nano‐ESI‐MS) to detect and identify the most frequently isolated dermatophytes from human and animal dermatophytosis in comparison with conventional methods. Results Among 200 samples, the identified species were Microsporum canis (78.22%), Trichophyton verrucosum (10.89%) and T. mentagrophytes (5.94%). Q‐PCR assay displayed great execution attributes for dermatophytes detection and identification. Using MALDI‐TOF MS, M. canis, but none of T. violacium, T. verrucosum or T. mentagrophytes, could be identified. Nano‐ESI‐MS accurately identified all species. The potential virulence attributes of secreted proteases were anticipated and compared between species. Secreted endoproteases belonging to families/subfamilies of metalloproteases, subtilisins and aspartic protease were detected. The analysed exoproteases are aminopeptidases, dipeptidyl peptidases and carboxypeptidases. Microsporum canis have three immunogenic proteins, siderophore iron transporter mirB, protease inhibitors, plasma membrane proteolipid 3 and annexin. Conclusion In essence, q‐PCR, MALDI‐TOF MS and nano‐ESI‐MS assays are very nearly defeating difficulties of dermatophytes detection and identification, thereby, supplement or supplant conventional diagnosis of dermatophytosis.

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Section: Discussionmentioning

confidence: 99%

Towards a rapid identification and a novel proteomic analysis for dermatophytes from human and animal dermatophytosis

Tartor

Hashem

Enany

2019

Mycoses

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“…It has also been reported that the sphingolipid-binding protein Pmp3, which is highly conserved in fungi, is a potent AmB resistance factor (71,72). Such resistance can be suppressed by the addition of phytosphingosine, a sphingolipid pathway intermediate (73).…”

Section: Amb Resistance In Pathogens Containing Normal Sterol Levelsmentioning

confidence: 99%

The Role of Signaling via Aqueous Pore Formation in Resistance Responses to Amphotericin B

Cohen

2016

Antimicrob Agents Chemother

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Drug resistance studies have played an important role in the validation of antibiotic targets. In the case of the polyene antibiotic amphotericin B (AmB), such studies have demonstrated the essential role that depletion of ergosterol plays in the development of AmB-resistant (AmB-R) organisms. However, AmB-R strains also occur in fungi and parasitic protozoa that maintain a normal level of ergosterol at the plasma membrane. Here, I review evidence that shows not only that there is increased protection against the deleterious consequences of AmB-induced ion leakage across the membrane in these resistant pathogens but also that a set of events are activated that block the cell signaling responses that trigger the oxidative damage produced by the antibiotic. Such signaling events appear to be the consequence of a membrane-thinning effect that is exerted upon lipid-anchored Ras proteins by the aqueous pores formed by AmB. A similar membrane disturbance effect may also explain the activity of AmB on mammalian cells containing Toll-like receptors. These resistance mechanisms expand our current understanding of the role that the formation of AmB aqueous pores plays in triggering signal transduction responses in both pathogens and host immune cells.

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“…Huang et al suggest that Pmp3p antagonizes the ergosterol-binding effect of amphotericin B, probably by preventing the insertion of amphotericin B into the plasma membrane (Huang et al, 2013). A recent study has shown that the amphotericin-B-treated phenotype of pmp3Δ can be modulated through the sphingolipid pathway (Bari et al, 2015). Reports by Bari et al and Huang et al both rule out an increase in ergosterol content as the source of the sensitivity to amphotericin B.…”

Section: Introductionmentioning

confidence: 99%

The yeast Pmp3p has a significant role in plasma membrane organization

Block

Szopinska

Guerriat

et al. 2015

Journal of Cell Science

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Pmp3p-related proteins are highly conserved proteins that exist in bacteria, yeast, nematodes and plants, and its transcript is regulated in response to abiotic stresses, such as low temperature or high salinity. Pmp3p was originally identified in Saccharomyces cerevisiae, and it belongs to the sensitive to Na + (SNA)-protein family, which comprises four members -Pmp3p/Sna1p, Sna2p, Sna3p and Sna4p. Deletion of the PMP3 gene conferred sensitivity to cytotoxic cations, whereas removal of the other SNA genes did not lead to clear phenotypic effects. It has long been believed that Pmp3p-related proteins have a common and important role in the modulation of plasma membrane potential and in the regulation of intracellular ion homeostasis. Here, we show that several growth phenotypes linked to PMP3 deletion can be modulated by the removal of specific genes involved in sphingolipid synthesis. These genetic interactions, together with lipid binding assays and epifluorescence microscopy, as well as other biochemical experiments, suggest that Pmp3p could be part of a phosphoinositide-regulated stress sensor.

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Plasma Membrane Proteolipid 3 Protein Modulates Amphotericin B Resistance throughSphingolipid Biosynthetic Pathway

Cited by 35 publications

References 55 publications

Towards a rapid identification and a novel proteomic analysis for dermatophytes from human and animal dermatophytosis

Towards a rapid identification and a novel proteomic analysis for dermatophytes from human and animal dermatophytosis

The Role of Signaling via Aqueous Pore Formation in Resistance Responses to Amphotericin B

The yeast Pmp3p has a significant role in plasma membrane organization

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