Microbiology insights最新文献

Echinocandin drugs target the fungal enzyme β-(1,3)-glucan synthase (GS), which is required for the synthesis of cell wall component β-(1,3)-d-glucan. They are first-line therapy for Candida infections but are increasingly used as second-line therapy for Aspergillus infections. Resistance to echinocandins has been mainly studied in Candida and occurs due to mutations in FKS genes encoding GS. In our recent report, we identified a novel mechanism of echinocandin resistance in Aspergillus fumigatus. We showed that caspofungin exposure modifies GS, rendering it insensitive to echinocandins. This mechanism of resistance involved alteration of the GS lipid microenvironment and was mediated via an off-target effect on mitochondria leading to increased reactive oxygen species (ROS). We hypothesized that caspofungin-induced ROS alters the lipid composition around GS, changing its conformation and making it insensitive to echinocandins. In this commentary, we review both fks1-dependent and fks1-independent mechanisms of echinocandin resistance in A fumigatus. We believe this new resistance mechanism is also conserved among Candida spp. with implications for drug tolerance and/or resistance. Furthermore, we propose that ROS acts as a signaling molecule regulating lipid biogenesis, which impacts the structure-function of membrane proteins with implications for other types of drug-target interactions.

Introduction: While acute respiratory tract infections are the main cause of paediatric mortality and morbidity worldwide, pathogen patterns shift due to factors such as hygiene, vaccinations, and antibiotic resistance. Knowledge about current cause of respiratory infections is lacking, particularly in low- and middle-income countries. The aim of this study was to identity the various respiratory pathogens causing acute respiratory tract infections in children below 5 years of age visiting a sub-urban primary care clinic in Senegal.

Methods: A case-control study was performed in September and October 2018. Oropharyngeal swabs were collected from cases; infants with fever and respiratory symptoms, and controls; children involved in the vaccination programme. Viral identification was conducted by polymerase chain reaction for 21 different viruses; bacteria were identified by culture studies. Associations between microorganisms, acute respiratory infection and severity of disease were calculated by multivariate regression adjusting for confounders such as age, sex, and living area.

Results: Overall, 102 cases and 96 controls were included. Microorganisms were detected in 90.1% of cases and 53.7% of controls (P < .001). Influenza virus A (including H1N1), influenza virus B, respiratory syncytial virus (RSV), and Streptococcus pneumoniae were independently associated with acute respiratory tract infections. Co-detection of two or more pathogens was present in 49.5% of cases; 31.7% of cases had a pneumonia and 90.2% was treated with antibiotics.

Conclusions: This case-control study in a primary care setting in sub-Saharan Africa found influenza virus A and B, RSV, and S pneumoniae to be the main causes of acute respiratory tract infections in children below 5 years of age. We recommend evaluation of antibiotics prescription behaviour in this setting.

Introduction: Influenza infection is a viral disease with significant morbidity and mortality during the cold months. Clinical presentation typically includes cough, fever, and pain. Influenza disease is hardly diagnosed only on the basis of clinical symptoms due to similar clinical presentation of other diseases such as a typical cold or other flu-like diseases. We evaluated patients with proven influenza who presented at an emergency department of internal medicine in a university hospital according to the clinical presentation and different age groups.

Materials and methods: From October 2017 to April 2018, 723 reverse transcription-polymerase chain reaction (RT-PCR) tests for influenza were performed in the emergency department on patients with suspected influenza diagnosed clinically. A total of 240 influenza-positive patients were retrospectively assessed for documented main symptoms, vital parameters, risk factors for an unfavorable course, hospitalization, and death.

Results: The mean age of influenza patients was 65 years. Overall, 30 patients were aged 18 to 39 years, 48 patients 40 to 59 years, and 162 patients ⩾60 years. Influenza B in 168 (70%) was predominant to 72 influenza A (mostly H1N1). In only 30% of the patients all three typical symptoms (cough, fever, and headache/myalgia) were documented. Headache or myalgia (with 34%) was rather uncommon in influenza B. Sudden onset was cited in only 5.4%; 57% of all influenza patients were in hospital for a mean of 7.1 days, and 5.8% of all influenza patients died. Patients aged above 60 years had more risk factors, showed typical symptoms less frequently, and were hospitalized longer than younger patients (<60 and <40 years).

Conclusions: At an emergency department of internal medicine, influenza-diseased patients are of higher age, show an increased number of comorbidities, and are more likely to have milder symptoms documented. Elderly patients with influenza have a higher hospitalization rate with a longer hospital stay as compared with younger patients.

Antimicrobial resistance poses a threat in the treatment of infectious diseases in Bangladesh as well as in the world. Multidrug-resistant (MDR) Enterobacteriaceae, the most common cause of one such infectious disease, urinary tract infection (UTI), has contributed to the escalating problem of selecting empiric antibiotics against UTIs. The aim of this study was to investigate the presence of the efflux pump in MDR Escherichia coli isolates from UTI in the North-East region of Bangladesh, to isolate and characterize the AcrAB-TolC efflux pump genes of these locally isolated strains and to do mutation analysis of the efflux pump repressor AcrR gene to understand the AcrAB-TolC efflux pump mechanism. In the presence of omeprazole, an efflux pump inhibitor, every MDR E. coli isolate showed increased susceptibility to at least 1 of the 7 antibiotics investigated, indicating that efflux pump might be involved in their antibiotic resistance. Omeprazole decreased the minimum inhibitory concentration of every antibiotics being investigated by 2- to 8-fold. DNA and the deduced amino acid sequences of the polymerase chain reaction (PCR) products analyzed by bioinformatics tools revealed that the chromosomal AcrAB-TolC and AcrR genes were present in all MDR and antibiotic-susceptible E. coli isolates. However, the deduced amino acid sequences of the amplification refractory mutation system (ARMS) PCR product of the AcrR gene revealed that the substitution of arginine to cysteine at position 45 of AcrR was observed only in the MDR E. coli whose antibiotic susceptibility increased in the presence of omeprazole. Data reported herein support the notion that the increased antibiotic susceptibility of the MDR E. coli isolates in the presence of omeprazole might be due to efflux pump(s) inhibition and the AcrAB-TolC efflux pump might be a contributor to antibiotic resistance when the mutation of arginine to cysteine occurs at position 45 of AcrR.

Objectives: To characterize hepatitis C testing in Massachusetts and guide stakeholders in addressing the needs of people living with hepatitis C.

Methods: All persons with a positive laboratory report for anti-hepatitis C virus (HCV) antibody, between 2014 and 2016, were included in the testing cascade. Outcomes were HCV tests received after a positive anti-HCV antibody test: nucleic acid test or genotype test. Logistic regression analyses were performed to determine factors associated with progression through the HCV testing cascade.

Results: Among those reported anti-HCV antibody positive, a total of 13 194 (61%) cases had a subsequent RNA-based test, and 79% (10 374/13 194) were confirmed with current, active HCV infection. For confirmed HCV cases, 44% (4557/10 374) had a genotype identified. The median time from an antibody-positive test to a RNA-based test was 29 days (interquartile range [IQR] = 7-151). Differences in moving through the testing cascade were observed by birth cohort and race/ethnicity.

Conclusions: Improved surveillance capture of demographic information is needed to help public health agencies ensure equity in HCV diagnosis and linkage to care.

The filamentous fungus Trichoderma reesei is traditionally used as the main industrial producer of cellulases and hemicellulases. Recently, the relevance of carbohydrases hydrolyzing nonstarch polysaccharides of cereals has significantly increased in feed production. In processing of grain raw materials, endodepolymerases, mainly xylanases and endoglucanases, play a key role. Earlier, we carried out gamma mutagenesis of an industrial strain T. reesei BCM18.2/KK to increase the proportion of endodepolymerases in its enzyme complex. Endoglucanase activity of the strain was increased 5-fold, while xylanase activity increased more than 8-fold. It was interesting to determine the carbohydrases composition in enzyme preparations obtained from the original and mutant T. reesei strains. So, the strains were cultured in laboratory fermenters; concentrated preparations were obtained using freeze dryer. It was established that gamma mutagenesis resulted in significant changes in the carbohydrases complex of the strain. Cellobiohydrolase I being the major carbohydrase in the original strain was absent in the enzyme complex of the mutant. The share of xylanases and endoglucanases in the preparation from the mutant strain increased by 6% and 6.5%, respectively, compared with the preparation from the original strain. The obtained data show the ability of gamma irradiation to affect the component composition of T. reesei carbohydrase complex.

Background: Recent animal and retrospective human studies have demonstrated that Schistosoma mansoni infection may have potential to protect against development of metabolic syndromes. Thus, the aim of this study was to assess metabolic panel among S. mansoni egg positives and egg negatives in stool examinations. This study was a cross-sectional study, conducted involving 120 participants from S. mansoni endemic town (Kemise) and 61 from non-endemic town (Kombolcha), Northeast Ethiopia. Stool samples were collected and examined for S. mansoni and other helminths using Kato-Katz method. Furthermore, blood samples were collected and used for determination of blood sugar, lipid profile tests, insulin, and C-reactive protein. Data were analyzed using SPSS software version 20. Chi-square test, independent mean t-test, and logistic regression models were employed on data. P values less than .05 were considered as statistically significant.

Results: S. mansoni infected participants (n = 41; all from Kemise) had significantly lower levels of fasting blood sugar, low prevalence of dyslipidemia (at least one or more abnormal lipid profile tests; total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides) as compared with controls (n = 79 in Kemise and 61 in Kombolcha). Moreover, logistic regression model indicated that with the adjusted odds ratios, there was significant inverse association between S. mansoni infection and impaired fasting glucose (adjusted odds ratio -0.181, 95% confidence interval: 0.042-0.774).

Conclusions: Low fasting blood sugar and reduced prevalence of dyslipidemia in S. mansoni egg positive participants might suggest inverse association of S. mansoni infection and development of metabolic syndromes. Furthermore, large-scale studies are recommended to assess the role of S. mansoni egg and/or worm antigens in modulating the host metabolic profile and reducing the risk of metabolic syndromes, including diabetes mellitus and cardiovascular diseases.