149 research outputs found
Paradigm Shift: Candida parapsilosis sensu stricto as the Most Prevalent Candida Species Isolated from Bloodstream Infections with Increasing Azole-Non-Susceptibility Rates: Trends from 2015–2022 Survey
No full textCandidemia is the fourth most common healthcare-related bloodstream infection. In recent years, incidence rates of Candida parapsilosis have been on the rise, with differences in prevalence and antifungal susceptibility between countries. The aim of the present study was to evaluate temporal changes in prevalence and antifungal susceptibility of C. parapsilosis among other species causing candidemia. All candidemia episodes from January 2015 to August 2022 were evaluated in order to depict time trends in prevalence of C. parapsilosis sensu stricto among all Candida species recovered from blood cultures as well as fluconazole- and voriconazole-non-susceptibility rates. Secondary analyses evaluated time trends in prevalence and antifungal non-susceptibility according to clinical settings. The overall prevalence of C. parapsilosis was observed to increase compared to the prevalence of other Candida species over time (p-trend = 0.0124). From 2019, the number of C. parapsilosis sensu stricto isolates surpassed C. albicans, without an increase in incidence rates. Overall rates of fluconazole- and voriconazole-non-susceptible C. parapsilosis sensu stricto were both 3/44 (6.8%) in 2015 and were 32/51 (62.7%) and 27/51 (52.9%), respectively, in 2022 (85% cross-non-susceptibility). The risk of detecting fluconazole- or voriconazole-non-susceptibility was found to be higher in C. parapsilosis compared to other Candida species (odds ratio (OR) = 1.60, 95% CI [1.170, 2.188], p-value < 0.0001 and OR = 12.867, 95% CI [6.934, 23.878], p-value < 0.0001, respectively). This is the first study to report C. parapsilosis sensu stricto as the most prevalent among Candida spp. isolated from blood cultures, with worrisome fluconazole- and voriconazole-non-susceptibility rates, unparalleled among European and North American geographical regions
Pushing the Limits of MALDI-TOF Mass Spectrometry: Beyond Fungal Species Identification
No full textMatrix assisted laser desorption ionization time of flight (MALDI–TOF) is a powerful analytical tool that has revolutionized microbial identification. Routinely used for bacterial identification, MALDI-TOF has recently been applied to both yeast and filamentous fungi, confirming its pivotal role in the rapid and reliable diagnosis of infections. Subspecies-level identification holds an important role in epidemiological investigations aimed at tracing virulent or drug resistant clones. This review focuses on present and future applications of this versatile tool in the clinical mycology laboratory
Synergistic Activity of the Human Lactoferricin-Derived Peptide hLF1-11 in Combination with Caspofungin against Candida Species
No full textCandida species are the main fungal opportunistic pathogens causing systemic infections that are often associated with drug resistance and biofilm production on medical devices. The pressing need for new antifungal agents led to an increased interest in the use of combination therapies. The present study was aimed at investigating potential synergistic activity of the human lactoferrin-derived hLF1-11 peptide with caspofungin against caspofungin-resistant or -susceptible C. albicans, C. parapsilosis, and C. glabrata strains. Synergism was evaluated by the checkerboard assay, measuring cellular metabolic activity against Candida planktonic and sessile cells. A fractional inhibitory concentration (FIC) index of ≤0.5 was interpreted as synergy. Synergism was evaluated by killing assays on planktonic cells. A cell viability assay was performed with biofilm formation inhibition and preformed biofilm. Synergy for killing and viability assays was defined as a ≥2-log-CFU/mL reduction in comparison with the most active constituent. hLF1-11 and caspofungin exerted (i) synergistic effects against planktonic cells of all the tested strains, yielding drastic caspofungin MIC reduction, (ii) synergistic effects on the inhibition of biofilm formation against biofilm producer strains, yielding caspofungin BIC reduction, and (iii) synergistic effects on preformed biofilm assessed by measuring metabolic activity (FIC range, 0.28 to 0.37) against biofilm-producing strains and by cell viability assay in C. albicans SC5314. The synergistic effect observed between caspofungin and hLF1-11 against Candida spp. is of potential clinical relevance, representing a promising novel approach to target caspofungin-resistant Candida species infections. Further studies elucidating the mechanisms of action of such a synergistic effect are needed. IMPORTANCE The present study describes a synergistic effect between a conventional antifungal drug, caspofungin, and a synthetic peptide derived from human lactoferrin, hLF1-11, against Candida species. These yeasts are able to cause severe systemic fungal infections in immunocompromised hosts. In addition, they can form biofilms in medical implanted devices. Recently, caspofungin-resistant Candida strains have emerged, thus highlighting the need to develop different therapeutic strategies. In in vitro studies, this drug combination is able to restore sensitivity to caspofungin in caspofungin-resistant strains of Candida species, both in free-living cells and in cells organized in biofilms. This synergism could represent a promising novel approach to target infections caused by caspofungin-resistant Candida species
Candida parapsilosis Sensu Stricto Antifungal Resistance Mechanisms and Associated Epidemiology
No full text: Fungal diseases cause millions of deaths per year worldwide. Antifungal resistance has become a matter of great concern in public health. In recent years rates of non-albicans species have risen dramatically. Candida parapsilosis is now reported to be the second most frequent species causing candidemia in several countries in Europe, Latin America, South Africa and Asia. Rates of acquired azole resistance are reaching a worrisome threshold from multiple reports as in vitro susceptibility testing is now starting also to explore tolerance and heteroresistance to antifungal compounds. With this review, the authors seek to evaluate known antifungal resistance mechanisms and their worldwide distribution in Candida species infections with a specific focus on C. parapsilosis
Genetic variation in PSCA and risk of gastric advanced preneoplastic lesions and cancer in relation to Helicobacter pylori infection.
No full textSNPs in the Prostate Stem Cell Antigen (PSCA) gene have been found associated with gastric cancer (GC) risk in a genome-wide association study. This association has been replicated in several populations. In this study we assessed the impact of PSCA genotype on the risk of advanced gastric precancerous lesions and GC. We used baseline gastric histopathology data and DNA from frozen gastric biopsies of 2045 subjects enrolled in a chemoprevention trial for gastric precancerous lesions in Venezuela, and 180 cases of GC from the same area. We analyzed 3 SNPs in the PSCA gene (rs2294008, rs9297976 and rs12155758) which were previously found to be associated with GC risk in Europeans. The T allele of rs2294008 was found to be associated with a higher prevalence of atrophic gastritis (OR = 1.44; 95% CI 1.03-2.01 for the dominant model) and intestinal metaplasia (OR = 1.50; 95% CI 1.13-1.98 for the dominant model). We also confirmed the association with higher risk of gastric cancer (OR = 2.34; 95% CI 1.36-4.01 for the allele carriers). SNP rs12155758 was not associated with risk of gastric preneoplastic lesions, but we confirmed its association with higher GC risk (OR 1.95; 95% CI 1.29-2.97 for dominant model). We tested the relevance of the presence of the Helicobacter pylori cagA gene, which is known to increase the risk of more severe gastric lesions, but we did not find any clearcut interaction with PSCA SNPs in defining risk of gastric precancerous lesions or cancer
Hospital distribution, seasonality, time trends and antifungal susceptibility profiles of all Aspergillus species isolated from clinical samples from 2015 to 2022 in a tertiary care hospital
No full textBackground: Aspergillus species cause a variety of serious clinical conditions with increasing trend in antifungal resistance. The present study aimed at evaluating hospital epidemiology and antifungal susceptibility of all isolates recorded in our clinical database since its implementation. Methods: Data on date of isolation, biological samples, patients' age and sex, clinical settings, and antifungal susceptibility tests for all Aspergillus spp. isolated from 2015 to 2022 were extracted from the clinical database. Score test for trend of odds, non-parametric Mann Kendall trend test and logistic regression analysis were used to analyze prevalence, incidence, and seasonality of Aspergillus spp. isolates. Results: A total of 1126 Aspergillus spp. isolates were evaluated. A. fumigatus was the most prevalent (44.1%) followed by A. niger (22.3%), A. flavus (17.7%) and A. terreus (10.6%). A. niger prevalence increased over time in intensive care units (p-trend = 0.0051). Overall, 16 (1.5%) were not susceptible to one azole compound, and 108 (10.9%) to amphotericin B, with A. niger showing the highest percentage (21.9%). The risk of detecting A. fumigatus was higher in June, (OR = 2.14, 95% CI [1.16; 3.98] p = 0.016) and reduced during September (OR = 0.48, 95% CI [0.27; 0.87] p = 0.015) and October as compared to January (OR = 0.39, 95% CI [0.21; 0.70] p = 0.002. A. niger showed a reduced risk of isolation from all clinical samples in the month of June as compared to January (OR = 0.34, 95% CI [0.14; 0.79] p = 0.012). Seasonal trend for A. flavus showed a higher risk of detection in September (OR = 2.7, 95% CI [1.18; 6.18] p = 0.019), October (OR = 2.32, 95% CI [1.01; 5.35] p = 0.048) and November (OR = 2.42, 95% CI [1.01; 5.79] p = 0.047) as compared to January. Conclusions: This is the first study to analyze, at once, data regarding prevalence, time trends, seasonality, species distribution and antifungal susceptibility profiles of all Aspergillus spp. isolates over a 8-year period in a tertiary care center. Surprisingly no increase in azole resistance was observed over time
Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11
No full textThe aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP) was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans
Sensitization of KPC and NDM Klebsiella pneumoniae To Rifampicin by the Human Lactoferrin-Derived Peptide hLF1-11
No full textA synergistic effect of non-bactericidal concentrations of the human lactoferrin (hLF)-derived peptide hLF1-11 and rifampicin against multidrug-resistant KPC (Klebsiella pneumoniae carbapenemase)-producing K. pneumoniae has been previously shown. The present study focuses on the mechanism(s) underlying this synergistic effect. The contribution of hLF1-11 and rifampicin to the synergistic effect was evaluated by killing assays with KPC K. pneumoniae cells incubated with hLF1-11 and, after washing, with rifampicin, or vice versa. Cell membrane permeability and polarization upon exposure to hLF1-11 and/or rifampicin were evaluated by ethidium bromide (EtBr) and DiBAC4(3) (bis-1,3-dibutylbarbituric acid trimethine oxonol) permeability, respectively. The effect of carbonyl cyanide m-chlorophenyl hydrazone (CCCP), an uncoupler of oxidative phosphorylation, was also evaluated. KPC K. pneumoniae cells were effectively killed after prior exposure to rifampicin for 30 to 60 min followed by treatment with hLF1-11, while no antibacterial activity was observed when cells were incubated with hLF1-11 first and then with rifampicin. EtBr accumulation increased upon exposure to hLF1-11 or the combination of hLF1-11 and rifampicin, but not upon exposure to rifampicin alone. Moreover, hLF1-11 induced a dose-dependent membrane depolarization. As expected, the antibacterial activity of hLF1-11 alone or combined with rifampicin was significantly reduced in the presence of CCCP. Furthermore, hLF1-11 and rifampicin were synergistic also against a colistin-resistant NDM (New Delhi metallo-β-lactamase)-producing K. pneumoniae strain. The results suggest that rifampicin was accumulated by KPC cells during the 30-to-60-min incubation and that the addition of hLF1-11 sensitized bacterial cells to rifampicin by inducing a transient loss of membrane potential and increased cell membrane permeability, thus facilitating the entrance and retention of rifampicin into the cytoplasm. IMPORTANCE The present study describes a synergistic effect between rifampicin, an impermeable hydrophobic antibiotic with an intracellular target, and an hLF1-11, an antimicrobial peptide derived from human lactoferrin, against multidrug-resistant Klebsiella pneumoniae. Carbapenem-resistant K. pneumoniae has recently caused an outbreak in Tuscany, Italy, thus pressing the need for the development of new treatment options. The mechanisms underlying such a synergistic effect have been studied. The results suggest that the synergistic effect was due to the transient loss of membrane potential induced by hLF1-11 and the subsequent increase in cell membrane permeability which allowed rifampicin to enter the bacterial cell. Therefore, it is likely that a sub-inhibitory concentration of hLF1-11 can efficiently permeabilize K. pneumoniae cells to rifampicin, allowing the antibiotic to reach its intracellular target. These results encourage further exploration of possible applications of this synergistic combination in the treatment of K. pneumoniae infections
Use of Amplification Fragment Length Polymorphism to genotype Pseudomonas stutzeri strains following exposure to ultraviolet light A
No full textChanges in ultraviolet light radiation can act as a selective force on the genetic and physiological traits of a microbial community. Two
strains of the common soil bacterium Pseudomonas stutzeri, isolated from aquifer cores and from human spinal fluid were exposed to
ultraviolet light. Amplification length polymorphism analysis (AFLP) was used to genotype this bacterial species and evaluate the effect
of UVA-exposure on genomic DNA extracted from 18 survival colonies of the two strains compared to unexposed controls. AFLP showed
a high discriminatory power, confirming the existence of different genotypes within the species and presence of DNA polymorphisms
in UVA-exposed colonies
Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review
No full textPancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, with a survival approaching only 11% at 5 years after diagnosis. In the last 15 years, telomere length (TL) measured in leukocyte (LTL) has been studied in relation to PDAC risk. The majority of the studies reported an association between short LTL and increased PDAC risk, but the results are heterogeneous. Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) in the telomerase reverse transcriptase (TERT) gene as susceptibility loci for PDAC. Polygenic risk scores computed using SNPs associated with LTL have been tested in relation to PDAC susceptibility with various methods and giving contrasting results. The aim of this review is to analyze all publications carried out specifically on LTL, considering LTL measured with qPCR and with genetic proxies, and PDAC risk. Additionally, we will give an overview of the most relevant associations between SNPs in telomere-associated genes and PDAC, to answer the question shorter or longer? Which one of the two is associated with PDAC risk
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