Multidrug-resistant bacteria such as methicillin-resistant
(MRSA) is one of the major causes of hospital-acquired and community infections and pose a challenge to the human health care system. ...Therefore, it is important to find new drugs that show activity against these bacteria, both in monotherapy and in combination with other antimicrobial drugs. Gliotoxin (GT) is a mycotoxin produced by
and other fungi of the
genus. Some evidence suggests that GT shows antimicrobial activity against
in vitro, albeit its efficacy against multidrug-resistant strains such asMRSA or vancomycin-intermediate
(VISA) strainsis not known. This work aimedto evaluate the antibiotic efficacy of GT as monotherapy or in combination with other therapeutics against MRSA in vitro and in vivo using a
infection model.
Background:
Antibiotic resistance and impaired wound healing are major concerns in
S. aureus
superficial skin infections, and new therapies are needed. Antimicrobial photodynamic therapy (aPDT) is a ...new therapeutic approach for infections, but it also improves healing in many wound models.
Objective:
To compare the antimicrobial activity and the effects on wound healing of aPDT based on Methylene Blue (MB-aPDT) with mupirocin treatment, either alone or in combination, in superficial skin wounds of
S. aureus
-infected mice. Additionally, to evaluate the clinical, microbiological, and cosmetic effects on wound healing.
Materials and Methods:
A superficial skin infection model of
S. aureus
was established in SKH-1 mice. Infected wounds were treated with MB-aPDT, MB-aPDT with a daily topical mupirocin or only with mupirocin. No treatment was carried out in control animals. Daily clinical and microbiological examinations were performed until complete clinical wound healing. Histopathological studies and statistical analysis were performed at the end of the study.
Results:
MB-aPDT treatment induced the best wound healing compared to mupirocin alone or to mupirocin plus MB-aPDT. Superficial contraction at 24 h and a greater reduction in size at 48 h, quicker detachment of the crust, less scaling, and absence of scars were observed. Histopathological studies correlated with clinical and gross findings. By contrast, mupirocin showed the highest logaritmic reduction of
S. aureus
.
Conclusions:
MB-aPDT and mupirocin treatments are effective in a murine superficial skin infection model of
S. aureus
. One session of MB-aPDT was the best option for clinical wound healing and cosmetic results. The addition of mupirocin to MB-aPDT treatment improved antimicrobial activity; however, it did not enhance wound healing. No synergistic antibacterial effects were detected.
Gliotoxin (GT) is a fungal secondary metabolite that has attracted great interest due to its high biological activity since it was discovered by the 1930s. An inactive derivative of this molecule, ...bis(methylthio)gliotoxin (bmGT), has been proposed as an invasive aspergillosis (IA) biomarker. Nevertheless, studies regarding bmGT production among common opportunistic fungi, including the
genus, are scarce and sometimes discordant. As previously reported, bmGT is produced from GT by a methyl-transferase, named as GtmA, as a negative feedback regulatory system of GT production. In order to analyze the potential of bmGT detection to enable identification of infections caused by different members of the
genus we have assessed bmGT production within the genus
, including
,
,
, and
, and its correlation with
presence. In order to validate the relevance of our
findings, we compared bmGT during
culture with the presence of bmGT in sera of patients from whom the
spp. were isolated. Our results indicate that most
isolates produce GT and bmGT both
and
. In contrast,
and
were not able to produce GT or bmGT, although
produced bmGT from a exogenous GT source. The frequency and amount of bmGT production in
and
isolates
was lower than in
. Our results suggest that this defect could be related to the
culture conditions, since isolates that did not produce bmGT
were able to synthetize it
. In summary, our study indicates that bmGT could be very useful to specifically detect the presence of
, the most prevalent agent causing IA. Concerning
and
a higher number of analyses from sera from infected patients will be required to reach a useful conclusion.
New strategies to fight bacteria and fungi are necessary in view of the problem of iatrogenic and nosocomial infections combined with the growing threat of increased antimicrobial resistance. ...Recently, our group has prepared and described two new readily available materials based on the combination of Rose Bengal (singlet oxygen photosensitizer) and commercially available cationic polystyrene (macroporous resin Amberlite® IRA 900 or gel-type resin IRA 400). These materials showed high efficacy in the antimicrobial photodynamic inactivation (aPDI) of
Pseudomonas aeruginosa
. Here, we present the photobactericidal effect of these polymers against an extended group of pathogens like
Escherichia coli, Enterococcus faecalis, Staphylococcus aureus
, and the opportunistic yeast
Candida albicans
using green light. The most interesting finding is that the studied materials are able to reduce the population of both Gram-positive and Gram-negative bacteria with good activity, although, for
C. albicans
, in a moderate manner. In view of the results achieved and especially considering the inexpensiveness of these two types of photoactive polymers, we believe that they could be used as the starting point for the development of coatings for self-disinfecting surfaces.
Hypericin is a natural photosensitizer considered for the new generation of photodynamic therapy (PDT) drugs. The aim of this study was to evaluate the in vitro fungicidal effect of hypericin PDT on ...various Candida spp., assessing its photocytotoxicity to keratinocytes (HaCaT) and dermal fibroblasts (hNDF) to determine possible side effects. A 3 log fungicidal effect was observed at 0.5 McFarland for two Candida albicans strains, Candida parapsilosis and Candida krusei with hypericin concentrations of 0.625, 1.25, 2.5 and 40 μm, respectively, at a fluence of 18 J cm−2 (LED lamp emitting at 602 ± 10 nm). To obtain a 6 log reduction, significantly higher hypericin concentrations and light doses were needed (C. albicans 5 μm, C. parapsilosis 320 μM and C. krusei 320 μM; light dose 37 J cm−2). Keratinocytes and fibroblasts can be preserved by keeping the hypericin concentration below 1 μm and the light dose below 37 J cm−2. C. albicans appears to be suitable for treatment with hypericin PDT without significant damage to cutaneous cells.
Photodynamic treatments using hypericin show a fungicidal effect on Candida spp., the most sensitive strain being Candida albicans and the most resistant Candida krusei. C. albicans infections could be suitable for treatment with hypericin PDT without significant damage to cutaneous cells.
Streptococcus agalactiae is a leading cause of sepsis and meningitis in newborns and young infants. Screening programs and intrapartum antibiotic prophylaxis have reduced early neonatal onset of ...disease. The aim of this study was to evaluate a molecular assay with lyophilized and ready-to-use reagents: VIASURE® Streptococcus B Real Time PCR detection kit (CerTest Biotec) (Viasure qPCR assay) compared to both the GBS culture and a molecular assay with separated and frozen reagents: Strep B Real-TM Quant (Sacace Biotecnologies®) (Sacace qPCR assay). A total of 413 vaginal−rectal swabs from women between the 35th and 37th weeks of pregnancy were processed. GBS culture was firstly achieved through Granada medium and Columbia CNA agar at 35 °C in aerobic conditions. Then, nucleic acid extraction was performed for subsequent molecular analysis using both commercial assays. Discordant results were resolved via bidirectional Sanger sequencing. Viasure qPCR assay clinical sensitivity was 0.97 (0.92−0.99) and specificity 1 (0.98−1). This retrospective study demonstrated the good clinical parameters and the strong overall agreement (99.3%) between the Viasure qPCR assay and both reference assays. Finally, the added value observed of the assay under study was the stabilized and ready-to-use format, reducing the number of time-consuming steps, permitting the storage at room temperature, facilitating transport, being environmentally respectful, and reducing additional costs.
Gliotoxin is a fungal secondary metabolite with impact on health and agriculture since it might act as virulence factor and contaminate human and animal food. Homologous gliotoxin (GT) gene clusters ...are spread across a number of fungal species although if they produce GT or other related epipolythiodioxopiperazines (ETPs) remains obscure. Using bioinformatic tools, we have identified homologous gli gene clusters similar to the
GT gene cluster in several fungal species. In silico study led to in vitro confirmation of GT and Bisdethiobis(methylthio)gliotoxin (bmGT) production in fungal strain cultures by HPLC detection. Despite we selected most similar homologous
gene cluster in 20 different species, GT and bmGT were only detected in section Fumigati species and in a
Q strain. Our results suggest that in silico gli homology analyses in different fungal strains to predict GT production might be only informative when accompanied by analysis about mycotoxin production in cell cultures.
Unfortunately this article 1 was published with an error. The following information was omitted: This study has received financial support from the national I + D + i 2013-2016 plan and been ...co-financed by the ISCII-General Subdirection of Evaluation and Promotion of Research and by the European Funds of Regional Development (FEDER) under Project reference PI13/01168.
Highlights • aPDT with RB and MB using a specific LED lamp has a significant bactericidal effect on S. mutans and S. sanguinis strains. • RB is slightly more efficient than MB. • Effects are the same ...in vitro either for separate bacteria or on the samples constituted by both bacteria.
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