Amebiasis is a disease caused by the protozoan parasite Entamoeba histolytica, which mainly shows symptoms of acute diarrhea, dysentery, amebic colitis, and amebic liver abscesses. As the fourth ...leading parasitic cause of human mortality, E. histolytica mainly infect children in developing countries, transmitted by food and water contamination. In the majority of infected individuals, Entamoeba sp. asymptomatically colonizes the large intestine and self-limiting, while in others, the parasite breaches the mucosal epithelial barrier to cause amebic colitis and can disseminate to soft organs to cause abscesses. Metronidazole (MTZ) is the recommended and most widely used drug for treating the invasive amebiasis. No amebiasis vaccine has been approved for human clinical trials to date, but many recent vaccine development studies hold promise. For the prevention and control of amebiasis, improvement of water purification systems and hygiene practices could decrease disease incidence. In this review, we focus on the epidemiology, transmission, clinical signs, pathogenesis, diagnosis, treatment, prevention and control of the zoonotic amebiasis.
•Amebiasis symptoms are mainly acute diarrhea, amebic colitis, amebic liver abscesses.•Entamoeba histolytica is the fourth leading parasitic cause of human mortality.•Metronidazole is the most widely used drug for treating the invasive amebiasis.•No amebiasis vaccine has been approved for human clinical trials, but hold promise.•Improvement of water sanitary and hygiene practices could decrease amebiasis incidence.
Rapid adaptation of metabolic capabilities is crucial for bacterial survival in habitats with fluctuating nutrient availability. In such conditions, the bacterial stringent response is a central ...regulatory mechanism activated by nutrient starvation or other stressors. This response is primarily controlled by exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) enzymes. To gain further insight into these enzymes, the high-resolution crystal structure of PPX from Zymomonas mobilis (ZmPPX) was determined at 1.8 Å. The phosphatase activity of PPX was strictly dependent on the presence of divalent metal cations. Notably, the structure of ZmPPX revealed the presence of two magnesium ions in the active site center, which is atypical compared to other PPX structures where only one divalent ion is observed. ZmPPX exists as a dimer in solution and belongs to the “long” PPX group consisting of four domains. Remarkably, the dimer configuration exhibits a substantial and deep aqueduct with positive potential along its interface. This aqueduct appears to extend towards the active site region, suggesting that this positively charged aqueduct could potentially serve as a binding site for polyP.
•Bacterial stringent response is regulated by PPX/GPPA enzymes.•The crystal structure of PPX from Zymomonas mobilis PPX was determined at 1.8 Å.•The structure displayed a ‘closed’ configuration advantageous to the slender polyP.•Two continuous magnesium ions were observed in the active center.•An aqueduct that runs along its interface is a potential binding site for polyP.
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•Bacterial polyphosphatase (PPX) hydrolyzes polyP and plays vital role in stringent response.•Structure of PPX was solved in complexed with substrate analogs and active magnesium ...ions.•The PPX possesses a more closed conformation and hydrolyzed polyP more efficiently.•Arg255 penetrates into the cavity and acts as a gatekeeper of the substrate entry channel.•These results provides insights into the molecular mechanism and substrate specifity.
The enzymes exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GppA) play important roles in the bacterial stringent response. PPX degrades inorganic polyphosphate (polyP), a polymer composed of a few to hundreds of phosphate residues supporting cell survival in the stationary phase. The crystal structure of PPX from Porphyromonas gingivalis (PgPPX) in complex with catalytic magnesium ions and several sulfate ions was solved. PgPPX contained two domains and represented a “closed” configuration. Four sulfate ions forming a linear dispersed chain were observed in the aqueduct of the PPX dimer, which the long polyP chain most likely occupied. The side chain of R255 stretched into the cavity where polyP could be located, obstructing the entrance of larger substrates such as NTP and NDP. This study provided the first view into the structure of the PPX/GppA homolog in complex with magnesium ions and substrate analogs and explained how PgPPX implemented its functionality.
Cryptosporidium is a protozoan parasite capable of infecting humans and animals and is a leading cause of diarrheal disease and early childhood mortality. The molecular mechanisms underlying invasive ...infection and its pathogenesis remain largely unknown. To better understand the molecular mechanism of the interaction between C. parvum and host cells, we profiled the changes of host cells membrane proteins extracted using native membrane protein extraction kit between C. parvum-infected HCT-8 cells and the control group after C. parvum infected 6 h combined with quantitative Tandem Mass Tags (TMT) liquid chromatography-dual mass spectrometry proteomic analysis. Among the 4844 quantifiable proteins identified, the expression levels of 625 were upregulated, and those of 116 were downregulated at 6 h post-infection compared with controls (1.5-fold difference in abundance, p < 0.05). Enrichment analysis of the function, protein domain and Kyoto Encyclopedia of Genes and Genomes pathway of the differentially expressed proteins revealed that the differentially expressed proteins were mainly related to biological functions related to the cytoskeleton and cytoplasmic matrix. We also found that infection with C. parvum may destroy HCT-8 intercellular space adhesion. Six proteins were further verified using quantitative real-time reverse transcription polymerase chain reaction and western blotting. Through systematic analysis of proteomics related to HCT-8 cell membranes infected by C. parvum, we found many host membrane proteins that can serve as potential receptors in C. parvum adhesion or invasion. C. parvum infection destroyed host cell barrier function and caused extensive changes in host cytoskeleton proteins, providing a deeper understanding of the molecules and their functions involved in the host-C. parvum interaction.
There is a lack of systematic research on the molecular mechanisms underlying the interaction of C. parvum with host cells. Changes of host cell membrane proteins after C. parvum infection may be used to examine the host cell receptors for parasite adhesion and invasion, and how the parasite interacts with these receptors. It is of great significance that host cells undergo membrane fusion to mediate invasion. Through proteomic studies on the host cell membrane after infection with HCT-8 cells by C. parvum, we observed disruption of the host cell cellular barrier function and widespread alteration of host cytoskeletal proteins caused by C. parvum infection, providing a deeper understanding of the molecules and their functions involved in host-C. parvum interaction.
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•C. parvum infection caused differential expression of 714 HCT-8 cells proteins, of which 625 were upregulated and 116 were downregulated.•we observed significant enrichment of Cell adhesion molecules (CAMs) signaling pathways in host cells caused by C. parvum infection.•C. parvum infection can destroy the cell barrier function of host cells and cause extensive changes in host cytoskeleton proteins.•The invasion of C. parvum may destroy adherens junctions between HCT-8 cells.
Introduction Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 ...illness. Methods We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions. Results Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0%) were patients with COVID-19, of whom 94.9% had at least 1 underlying medical condition. Essential hypertension (50.4%), disorders of lipid metabolism (49.4%), and obesity (33.0%) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio aRR = 1.30; 95% CI, 1.27–1.33), anxiety and fear-related disorders (aRR = 1.28; 95% CI, 1.25–1.31), and diabetes with complication (aRR = 1.26; 95% CI, 1.24–1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95% CI, 1.41–1.67) for patients with 1 condition to 3.82 (95% CI, 3.45–4.23) for patients with more than 10 conditions (compared with patients with no conditions). Conclusion Certain underlying conditions and the number of conditions were associated with severe COVID-19 illness. Hypertension and disorders of lipid metabolism were the most frequent, whereas obesity, diabetes with complication, and anxiety disorders were the strongest risk factors for severe COVID-19 illness. Careful evaluation and management of underlying conditions among patients with COVID-19 can help stratify risk for severe illness.
Enterocytozoon bieneusi is an emerging zoonotic intestinal pathogen that infects humans and various animal species. Here, we aimed to determine the infection rate and genetic characteristics of E. ...bieneusi from bamboo rats from different regions of China using nested polymerase chain reaction-based amplification of the internal transcribed spacer region of the rRNA gene. A total of 435 bamboo rats fecal samples were collected from individual tank from Guangdong, Hunan, Jiangxi, Chongqing, and Guangxi, southeastern China. E. bieneusi was detected on 22 tanks (5.1%, 22/435), with a higher infection rate being observed among samples from Guangdong Province (10.9%, 5/46) compared with those from Hunan (9.3%, 10/107), Jiangxi (6.7%, 6/90), Chongqing (2.0%, 1/50), and Guangxi (0%, 0/142) (P < .01). Six genotypes were identified, including four known genotypes (D, EbpA, J, and PigEBITS7) and two novel genotypes (named BR1 and BR2). Of these, zoonotic genotype D was the most prevalent in the present study (n = 17). Phylogenetic analysis revealed that genotypes D, EbpA, and PigEBITS7 were clustered into Group 1, while genotypes J, BR1, and BR2 were clustered into Group 2. To our knowledge, this is the first report of E. bieneusi in bamboo rats. The identification of zoonotic genotype D as the predominant genotype in bamboo rats suggests that these animals represent a potential zoonotic risk for the transfer of the pathogen in China.
•The bamboo rats represent a potential zoonotic risk for the transfer of E. bieneusi in China.•Four known genotypes and two novel genotypes were identified.•Zoonotic genotype D was the most prevalent in the present study.
Case-control studies are commonly used to explore factors associated with enteric bacterial diseases. Control of confounding is challenging due to a large number of exposures of interest and the low ...frequencies of many of them.
We evaluated nearest-neighbors matching in a case-control study (originally 1:1 matched, published in 2004) of sporadic Campylobacter infections that included information on 433 exposures in 2632 subjects during 1998-1999. We performed multiple imputations of missing data (m = 100) and calculated Gower distances between cases and controls using all possible confounders for each exposure in each dataset. We matched each case with ≤20 controls within a data-determined distance. We calculated odds ratios and population attributable fractions (PAFs).
Examination of pairwise correlation between exposures found very strong associations for 1046 pairs of exposures. More than 100 exposures were associated with campylobacteriosis, including nearly all risk factors identified using the previously published approach that included only 16 exposures and some less studied, rare exposures such as consumption of chicken liver and raw clams. Consumption of chicken and nonpoultry meat had the highest PAFs (62% and 59%, respectively).
Nearest-neighbors matching appear to provide an improved ability to examine rare exposures and better control for numerous highly associated confounders.
Objective
To determine the number and proportion of American adults recommended for weight loss treatment under the 1998 and 2013 guidelines on the management of overweight and obesity in adults and ...to compare characteristics of individuals recommended for treatment.
Methods
A total of 6,692 adult, non‐pregnant participants in the National Health and Nutrition Examination Survey 2007‐2012 with complete data on demographics, anthropometrics, and biomedical measures were analyzed.
Results
Compared to the 1998 guidelines, the 2013 guidelines increased the number of adults recommended for weight loss treatment by 20.9% from 116.0 million to 140.2 million, making 64.5% of non‐pregnant, non‐institutionalized US adults candidates for treatment. The new guidelines recommended treatment for a larger proportion of those overweight, having only one risk factor, or having a large waist circumference. Up to 53.4% of adults could be considered for pharmacologic therapy in addition to lifestyle therapy, and up to 14.7% could be considered for bariatric surgery.
Conclusions
The 2013 guidelines increased the number of adults to be treated with weight loss by 24.2 million, with the increases spread across groups that differ in socio demographic characteristics.
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