- Volume 64, Issue 11, 2015
Volume 64, Issue 11, 2015
- Microbial Ecology and Health
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Genes encoding ten newly designated OXA-63 group class D β-lactamases identified in strains of the pathogenic intestinal spirochaete Brachyspira pilosicoli
More LessThe anaerobic spirochaete Brachyspira pilosicoli colonizes the large intestine of birds and mammals, including human beings, and may induce colitis and diarrhoea. B. pilosicoli has a recombinant population structure, and strains show extensive genomic rearrangements and different genome sizes. The resident chromosomal gene bla OXA-63 in B. pilosicoli encodes OXA-63, a narrow-spectrum group IV class D β-lactamase. Genes encoding four OXA-63 variants have been described in B. pilosicoli, and the current study was designed to investigate the distribution and diversity of such genes and proteins in strains of B. pilosicoli. PCRs were used to amplify bla OXA-63 group genes from 118 B. pilosicoli strains from different host species and geographical origins. One primer set was targeted externally to the gene and two sets were designed to amplify internal components. A total of 16 strains (13.6 %) showed no evidence of possessing bla OXA-63 group genes, 44 (37.3 %) had a full gene, 27 (22.9 %) apparently had a gene but it failed to amplify with external primers, and 29 (24.6 %) had only one or other of the two internal components amplified. Based on translation of the nucleotide sequences, ten new variants of the β-lactamase, designated OXA-470 through OXA-479, were identified amongst the 44 strains that had the full gene amplified. The 16 strains lacking bla OXA-63 group genes had a region of 1674 bp missing around where the gene was expected to reside. Despite apparent genomic rearrangements occurring in B. pilosicoli, positive selection pressures for conservation of bla OXA-63 group genes and OXA proteins appear to have been exerted.
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- Prevention and Therapy
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Miltefosine is effective against Candida albicans and Fusarium oxysporum nail biofilms in vitro
More LessOnychomycosis is a fungal nail infection that represents ∼50 % of all nail disease cases worldwide. Clinical treatment with standard antifungals frequently requires long-term systemic therapy to avoid chronic disease. Onychomycosis caused by non-dermatophyte moulds, such as Fusarium spp., and yeasts, such as Candida spp., is particularly difficult to treat, possibly due to the formation of drug-resistant fungal biofilms on affected areas. Here, we show that the alkylphospholipid miltefosine, used clinically against leishmaniasis and cutaneous breast metastases, has potent activity against biofilms of Fusarium oxysporum and Candida albicans formed on human nail fragments in vitro. Miltefosine activity was compared with that of commercially available antifungals in the treatment of biofilms at two distinct developmental phases: formation and maturation (pre-formed biofilms). Drug activity towards biofilms formed on nail fragments and on microplate surfaces (microdilution assays) was evaluated using XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assays, and drug effects on fingernail biofilms were analysed by scanning electron microscopy (SEM). For F. oxysporum, miltefosine at 8 μg ml− 1 inhibited biofilm formation by 93 %, whilst 256 μg ml− 1 reduced the metabolic activity of pre-formed nail biofilms by 93 %. Treatment with miltefosine at 1000 μg ml− 1 inhibited biofilm formation by 89 % and reduced the metabolic activity of pre-formed C. albicans biofilms by 99 %. SEM analyses of biofilms formed on fingernail fragments showed a clear reduction in biofilm biomass after miltefosine treatment, in agreement with XTT results. Our results show that miltefosine has potential as a therapeutic agent against onychomycosis and should be considered for in vivo efficacy studies, especially in topical formulations for refractory disease treatment.
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- Correspondence
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Volumes and issues
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Volume 73 (2024)
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Volume 72 (2023 - 2024)
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Volume 71 (2022)
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Volume 70 (2021)
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Volume 69 (2020)
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Volume 68 (2019)
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Volume 67 (2018)
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Volume 65 (2016)
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Volume 64 (2015)
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Volume 63 (2014)
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