The Mammalian Pathogenic Oomycetes

Mendoza, Leonel; Vilela, Raquel

doi:10.1007/s12281-013-0144-z

Cited by 58 publications

(83 citation statements)

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“…Recent reports of novel mammalian Oomycota species in the genus Lagenidium introduced a new level of complexity for the identification of these Oomycota pathogens in the laboratory (Mendoza & Vilela 2013;Vilela et al, 2015). Infections caused by these unusual straminopilan fungal-like organisms are often fatal and occur in otherwise healthy hosts (Brown et al, 2008;Grooters et al, 2003).…”

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confidence: 99%

A biochemical screening approach to putatively differentiate mammalian pathogenic Oomycota species in the clinical laboratory

Vilela

Viswanathan

Mendoza

2015

Journal of Medical Microbiology

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The report of four novel mammalian pathogenic species of the genus Lagenidium prompted us to study the use of biochemical assays to differentiate the Oomycota mammalian pathogens Pythium insidiosum and Lagenidium spp. We investigated the reaction of 23 Lagenidium and eight Pythium species in various biochemical assays. Because the morphological features of the Oomycota species are similar to those of species in the Entomophthoramycota and Mucormycota, five fungal species with coenocytic hyphae were also included. We found that mammalian and plant isolates of Pythium spp. all hydrolysed sucrose, but Lagenidium species and the fungal strains did not. In addition, both Pythium spp. and Lagenidium spp. were found to be maltose-positive, whereas fungal strains did not hydrolyse this sugar. The fungal species and thermo-sensitive Lagenidium giganteum and Lagenidium humanum were urease-negative, but the mammalian Lagenidium spp. and Pythium spp. hydrolysed urea within 24 h. These findings suggest these assays can be used for the presumptive differentiation of mammalian Oomycota species in the laboratory.

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Section: Introductionmentioning

confidence: 99%

A biochemical screening approach to putatively differentiate mammalian pathogenic Oomycota species in the clinical laboratory

Vilela

Viswanathan

Mendoza

2015

Journal of Medical Microbiology

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“…ythiosis is a life-threatening and chronic pyogranulomatous disease caused by the fungus-like pathogen Pythium insidiosum, the main oomycete species capable of infecting humans and other animals (1,2). Although there have been a few reports of clinical cures of cases of pythiosis with antifungal therapy (3,4), the data from the literature on the clinical management of pythiosis patients with treatment by antifungals indicate that such therapy has been largely ineffective (2,5,6).…”

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New Insights into the In Vitro Susceptibility of Pythium insidiosum

Loreto

Tondolo

Pilotto

et al. 2014

Antimicrob Agents Chemother

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bWe have determined the in vitro activity of several antibacterial and antifungal drugs against Pythium insidiosum using broth microdilution (BMD), disk diffusion, and Etest methods. The largest zones of inhibition (disk diffusion) and the lowest BMD and Etest MICs were observed for azithromycin, clarithromycin, linezolid, mupirocin, doxycycline, minocycline, and tigecycline. The in vitro activities observed suggest that antibacterials, which act by inhibiting protein synthesis, are promising candidate therapies for the treatment of pythiosis. P ythiosis is a life-threatening and chronic pyogranulomatous disease caused by the fungus-like pathogen Pythium insidiosum, the main oomycete species capable of infecting humans and other animals (1, 2). Although there have been a few reports of clinical cures of cases of pythiosis with antifungal therapy (3, 4), the data from the literature on the clinical management of pythiosis patients with treatment by antifungals indicate that such therapy has been largely ineffective (2,5,6). The genus Pythium is unable to synthesize ergosterol, the active target of most antifungals, which partly explains why this class of drugs has been ineffective (2).Studies on the in vitro susceptibility of the clinical isolates of P. insidiosum to antifungal drugs have shown divergent results, and there are no international protocols approved for evaluating the in vitro susceptibility of P. insidiosum. Interestingly, previous studies have shown that P. insidiosum is quite sensitive to antibacterials belonging to the classes of macrolides, tetracyclines, and glycylcyclines (7,8) and that its combination with antifungal drugs can result in synergistic interactions in vitro (9). However, the effects of antibacterial agents that inhibit protein synthesis on P. insidiosum have not been studied extensively. Thus, the objective of this study was to compare the in vitro susceptibilities of P. insidiosum to a number of antibacterial and antifungal drugs using the Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth microdilution, CLSI M51-A disk diffusion, and Etest methods.We evaluated the susceptibility of 25 Brazilian P. insidiosum strains isolated from equine pythiosis lesions. All of the isolates were identified using a PCR-based assay according to Botton et al. (10). The reference strains included P. insidiosum CBS 101555 from an equine pythiosis case and P. insidiosum CBS 119452 and Pythium aphanidermatum CBS 128995 from human pythiosis cases.The broth microdilution (BMD) reference assay was carried out following the CLSI M38-A2 guidelines (11), as previously described (12, 13). The final concentrations of the antimicrobial agents tested in the wells ranged from 1,024 to 0.5 g/ml for mupirocin and tobramycin and from 256 to 0.125 g/ml for azithromycin, clarithromycin, clindamycin, chloramphenicol, doxycycline, erythromycin, florfenicol, fluconazole, fusidic acid, lincomycin, linezolid, minocycline, roxithromycin, terbinafine, tetracycline, tigecycline, and tilmicosin. The final conce...

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“…Consequently, there are no definitive treatment protocols for this disease, and despite some contradictory results, P. insidiosum can be considered intrinsically resistant to most antifungal drugs (2)(3)(4). The most commonly used effective clinical management of pythiosis is aggressive surgical resection, such as amputation, and surgical debridement of skin lesions.…”

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“…Unfortunately, surgical interventions are not always possible, and a high rate of recurrence has been observed. Additionally, immunotherapy cure rates can reach approximately 55% and 80% in humans and horses, respectively (2,3,5). Independent of the use of single or combination therapies, the best cure rates are associated with rapid diagnosis and early treatment (1,2).…”

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In Vitro Synergism between Azithromycin or Terbinafine and Topical Antimicrobial Agents against Pythium insidiosum

Itaqui

Verdi

Tondolo

et al. 2016

Antimicrob Agents Chemother

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bWe describe here in vitro activity for the combination of azithromycin or terbinafine and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate. With the exception of potassium permanganate, the remaining antimicrobial drugs were active and had an MIC 90 between 2 and 32 g⁄ml. The greatest synergism was observed for the combination of terbinafine and cetrimide (71.4%). In vivo experimental evaluations will clarify the potential of these drugs for the topical treatment of lesions caused by Pythium insidiosum. Pythium insidiosum is the main oomycete pathogen associated with severe diseases in humans and animals, particularly horses and dogs. In humans, clinical presentations include ocular, cutaneous⁄subcutaneous, vascular, and disseminated pythiosis. While underlying diseases, such as thalassemia and hemoglobinopathy syndrome, have been observed in cutaneous, vascular, and disseminated forms of disease, ocular pythiosis can affect otherwise healthy individuals. Moreover, no underlying diseases have been observed with animal pythiosis, for which most cases are associated with pyogranulomatous disease in subcutaneous tissue or in a gastrointestinal form (1, 2).Treating pythiosis remains a challenge because this microorganism produces hyaline hyphae similar to those of true fungi but is unable to synthesize ergosterol, which is the direct or indirect main target of most antifungal drugs. Consequently, there are no definitive treatment protocols for this disease, and despite some contradictory results, P. insidiosum can be considered intrinsically resistant to most antifungal drugs (2-4). The most commonly used effective clinical management of pythiosis is aggressive surgical resection, such as amputation, and surgical debridement of skin lesions. Unfortunately, surgical interventions are not always possible, and a high rate of recurrence has been observed. Additionally, immunotherapy cure rates can reach approximately 55% and 80% in humans and horses, respectively (2, 3, 5). Independent of the use of single or combination therapies, the best cure rates are associated with rapid diagnosis and early treatment (1, 2). Regardless of the therapy of choice, little attention has been given to the specific topical treatment of pythiosis lesions.Considering the high tissue concentrations achieved by azithromycin and terbinafine and the above context, this study aimed to assess the in vitro activity for combinations of azithromycin or terbinafine (systemic therapeutic options) and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate (topical therapeutic options).We evaluated the susceptibility of 20 isolates of P. insidiosum from equine pythiosis cases and the reference strain ATCC 58637. Clinical isolates were previously identified by a nested PCR assay (6). The drugs (final concentrations tested in the wells) azithromycin (0.06 to 32 g⁄ml), benzalkonium chloride (0.25 to 32 g⁄ml), alkyltrimethylammonium bromide (cetrimide) (0.5 to 32 g⁄ml), cetylpyrid...

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The Mammalian Pathogenic Oomycetes

Cited by 58 publications

References 50 publications

A biochemical screening approach to putatively differentiate mammalian pathogenic Oomycota species in the clinical laboratory

A biochemical screening approach to putatively differentiate mammalian pathogenic Oomycota species in the clinical laboratory

New Insights into the In Vitro Susceptibility of Pythium insidiosum

In Vitro Synergism between Azithromycin or Terbinafine and Topical Antimicrobial Agents against Pythium insidiosum

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