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MSystems Jun 2024Relationships between bacterial taxa are traditionally defined using 16S rRNA nucleotide similarity or average nucleotide identity. Improvements in sequencing technology...
UNLABELLED
Relationships between bacterial taxa are traditionally defined using 16S rRNA nucleotide similarity or average nucleotide identity. Improvements in sequencing technology provide additional pairwise information on genome sequences, which may provide valuable information on genomic relationships. Mapping orthologous gene locations between genome pairs, known as synteny, is typically implemented in the discovery of new species and has not been systematically applied to bacterial genomes. Using a data set of 378 bacterial genomes, we developed and tested a new measure of synteny similarity between a pair of genomes, which was scaled onto 16S rRNA distance using covariance matrices. Based on the input gene functions used (i.e., core, antibiotic resistance, and virulence), we observed varying topological arrangements of bacterial relationship networks by applying (i) complete linkage hierarchical clustering and (ii) K-nearest neighbor graph structures to synteny-scaled 16S data. Our metric improved clustering quality comparatively to state-of-the-art average nucleotide identity metrics while preserving clustering assignments for the highest similarity relationships. Our findings indicate that syntenic relationships provide more granular and interpretable relationships for within-genera taxa compared to pairwise similarity measures, particularly in functional contexts.
IMPORTANCE
Given the prevalence and necessity of the 16S rRNA measure in bacterial identification and analysis, this additional analysis adds a functional and synteny-based layer to the identification of relatives and clustering of bacteria genomes. It is also of computational interest to model the bacterial genome as a graph structure, which presents new avenues of genomic analysis for bacteria and their closely related strains and species.
PubMed: 38940518
DOI: 10.1128/msystems.00497-24 -
MSphere Jun 2024is an enteric pathogen that can cause a range of illnesses from mild diarrhea to pseudomembranous colitis and even death. This pathogen often takes advantage of...
UNLABELLED
is an enteric pathogen that can cause a range of illnesses from mild diarrhea to pseudomembranous colitis and even death. This pathogen often takes advantage of microbial dysbiosis provoked by antibiotic use. With the increasing incidence and severity of infections, coupled with high recurrence rates, there is an urgent need to identify innovative therapies that can preserve the healthy state of the gut microbiota. In this study, we screened a microbial metabolite library against . From a collection of 527 metabolites, we identified 18 compounds with no previously identified antimicrobial activity and metabolites that exhibited potent activity against growth. Of these 18 hits, five drugs and three metabolites displayed the most potent anti-. activity and were subsequently assessed against 20 clinical isolates of . These potent agents included ecteinascidin 770 (minimum inhibitory concentration against 50% of isolates [MIC] ≤0.06 µg/mL); 8-hydroxyquinoline derivatives, such as broxyquinoline and choloroquinaldol (MIC = 0.125 µg/mL); ionomycin calcium salt, carbadox, and robenidine hydrochloride (MIC = 1 µg/mL); and dronedarone and milbemycin oxime (MIC = 4 µg/mL). Unlike vancomycin and fidaxomicin, which are the standard-of-care anti-. antibiotics, most of these metabolites showed robust bactericidal activity within 2-8 h with minimal impact on the growth of representative members of the normal gut microbiota. These results suggest that the drugs and microbial metabolite scaffolds may offer alternative avenues to address unmet needs in disease prevention and treatment.
IMPORTANCE
The most frequent infection associated with hospital settings is , which can cause fatal diarrhea and severe colitis, toxic megacolon, sepsis, and leaky gut. Those who have taken antibiotics for other illnesses that affect the gut's healthy microbiota are more susceptible to infection (CDI). Recently, some reports showed higher recurrence rates and resistance to anti-, which may compromise the efficacy of CDI treatment. Our study is significant because it is anticipated to discover novel microbial metabolites and drugs with microbial origins that are safe for the intestinal flora, effective against , and reduce the risk of recurrence associated with CDI.
PubMed: 38940508
DOI: 10.1128/msphere.00273-24 -
MSphere Jun 2024The adaptation of gene deletion methods based on the CRISPR-Cas9 system has facilitated the genetic manipulation of the pathogenic yeast , because homozygous mutants of...
Probing gene function in wild-type strains by Cas9-facilitated one-step integration of two dominant selection markers: a systematic analysis of recombination events at the target locus.
UNLABELLED
The adaptation of gene deletion methods based on the CRISPR-Cas9 system has facilitated the genetic manipulation of the pathogenic yeast , because homozygous mutants of this diploid fungus can now be generated in a single step, allowing the rapid screening of candidate genes for their involvement in a phenotype of interest. However, the Cas9-mediated double-strand breaks at the target site may result in an undesired loss of heterozygosity (LOH) on the affected chromosome and cause phenotypic alterations that are not related to the function of the investigated gene. In our present study, we harnessed Cas9-facilitated gene deletion to probe a set of genes that are constitutively overexpressed in strains containing hyperactive forms of the transcription factor Mrr1 for a possible contribution to the fluconazole resistance of such strains. To this aim, we used gene deletion cassettes containing two different dominant selection markers, and , which confer resistance to nourseothricin and hygromycin, respectively, for simultaneous genomic integration in a single step, hypothesizing that this would minimize undesired LOH events at the target locus. We found that selection for resistance to both nourseothricin and hygromycin strongly increased the proportion of homozygous deletion mutants among the transformants compared with selection on media containing only one of the antibiotics, but it did not avoid undesired LOH events. Our results demonstrate that LOH on the target chromosome is a significant problem when using Cas9 for the generation of gene deletion mutants, which demands a thorough examination of recombination events at the target site.
IMPORTANCE
is one of the medically most important fungi and a model organism to study fungal pathogenicity. Investigating gene function in this diploid yeast has been facilitated by the adaptation of gene deletion methods based on the bacterial CRISPR-Cas9 system, because they enable the generation of homozygous mutants in a single step. We found that, in addition to increasing the efficiency of gene replacement by selection markers, the Cas9-mediated double-strand breaks also result in frequent loss of heterozygosity on the same chromosome, even when two different selection markers were independently integrated into the two alleles of the target gene. Since loss of heterozygosity for other genes can result in phenotypic alterations that are not caused by the absence of the target gene, these findings show that it is important to thoroughly analyze recombination events at the target locus when using Cas9 to generate gene deletion mutants in .
PubMed: 38940507
DOI: 10.1128/msphere.00388-24 -
Animal Models and Experimental Medicine Jun 2024Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant... (Review)
Review
Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between the gut microbiota and the host, SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics, activating G protein-coupled receptors, and inhibiting pathogenic microbial infections. This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health, enhancing energy metabolism, mitigating diseases such as cancer, obesity, and diabetes, modulating the gut-brain axis and gut-lung axis, and promoting bone health.
PubMed: 38940192
DOI: 10.1002/ame2.12464 -
Annals of Agricultural and... Jun 2024The NAA10 gene encodes N-alpha-acetyltransferase 10 which plays an important role in cell growth, differentiation, DNA damage, metastasis, apoptosis, stress response and... (Review)
Review
The NAA10 gene encodes N-alpha-acetyltransferase 10 which plays an important role in cell growth, differentiation, DNA damage, metastasis, apoptosis, stress response and autophagy. Defects in the NAA10 gene correlate with the diagnosis of NAA10-related syndrome (Ogden syndrome). The most common symptoms of NAA10-related syndrome are: global developmental delay, non-verbal or limited speech, autism spectrum disorder, feeding difficulties, motor delay, muscle tone disturbances, and long QT syndrome. To-date, there are about 100 patients who have been reported with this condition. The case report presents the clinical study of a girl aged 4 years and 3 months diagnosed with Ogden syndrome. She had many characteristic features of the disorder, as well as precocious puberty. This girl represents the case of a patient with p.Arg83Cys mutation in NAA10 gene as well as precocious puberty.
Topics: Humans; Female; Puberty, Precocious; N-Terminal Acetyltransferase A; N-Terminal Acetyltransferase E; Child, Preschool; Mutation
PubMed: 38940118
DOI: 10.26444/aaem/171758 -
Annals of Agricultural and... Jun 2024. Pets infected with zoonotic pathogens might become a source of infections for their owners, especially those who are immuno-compromised. The aim of this report is to...
. Pets infected with zoonotic pathogens might become a source of infections for their owners, especially those who are immuno-compromised. The aim of this report is to describe a case of chronic, untreatable pneumonia in a domestic ferret. The subject was a 5-year-old female ferret suffering from recurrent pneumonia. Ante-mortally, swabs from the nasal cavity, alveolus and throat were collected from the animal. Post-mortally, lesioned organ fragments were collected. Standard microbiological testing was performed. Additionally, mycobacterial diagnosis including culture and molecular tests was performed. . The co-infection of Mycobacterium avium and Klebsiella pneumoniae was microbiologically confirmed. This case demonstrates the need to pay attention to the possibility of zoonotic pathogens in ferrets. Veterinarians diagnosing ferrets are potentially exposed to Mycobacteria spp. infections and other pathogens.
Topics: Animals; Ferrets; Female; Klebsiella pneumoniae; Coinfection; Klebsiella Infections; Mycobacterium avium; Tuberculosis; Fatal Outcome
PubMed: 38940116
DOI: 10.26444/aaem/174216 -
Annals of Agricultural and... Jun 2024Morphological anomalies are considered a rare phenomenon among natural tick populations. New cases of abnormalities in ticks are being described, such as body...
Morphological anomalies are considered a rare phenomenon among natural tick populations. New cases of abnormalities in ticks are being described, such as body assymetries, nanism, gynandromorphism and limb malformations. The tick removed from a cat was morphologically identified to species and developmental stage. The time of feeding on the host was determined. The specimen was tested using PCR and Real-Time PCR methods for the presence of the common tick-borne pathogens: , spp, spp., , spp. For visualisation of the anomalous structures, scanning electron microscopy (SEM) was performed. The tick was identified as a slightly engorged adult female of I. ricinus exhibiting ectromely of leg I on the left side of the idiosoma. The specimen was tested positive for two medically important pathogens: and . The case report describes a rare case of a morphological anomaly in an tick from Poland.
Topics: Animals; Poland; Ixodes; Female; Cats; Cat Diseases; Anaplasma phagocytophilum; Tick Infestations
PubMed: 38940115
DOI: 10.26444/aaem/172533 -
Annals of Agricultural and... Jun 2024Intestinal parasitoses are important causes of morbidity and mortality, especially in immunocompromised individuals. In patients with chronic renal insufficiency (CRI),...
INTRODUCTION AND OBJECTIVE
Intestinal parasitoses are important causes of morbidity and mortality, especially in immunocompromised individuals. In patients with chronic renal insufficiency (CRI), the accumulation of non-excreted metabolites leads to uraemia, which induces a state of immunodeficiency, increasing the incidence of infections. The aim of the study was molecular screening for enteric protozoa in patients with chronic renal insufficiency.
MATERIAL AND METHODS
A total of 53 samples were collected in January 2023 from patients undergoing dialysis at Logman Ltd. Nephrodialysis Centre in Košice, Slovakia. Samples were examined by polymerase chain reaction (PCR) for the presence of / , , Microsporidia spp., and sp.
RESULTS
From the 53 samples, the only pathogen identified by PCR was Blastocystis sp., in 13 patients (24.5 %). Sequence analyses confirmed that the most prevalent subtype (ST) among patients was ST 3 (n=9, 69.2%), followed by ST 1 (n=3, 23.1%) and ST 2 (n=1, 7.7%).
CONCLUSIONS
Molecular methods for the detection of microscopic enteric parasites are not used as a first-line diagnostic method in Slovakia. In immunocompromised patients, diarrhoea can be caused not only by a chronic disease or therapy but can also be a result of an ongoing underdiagnosed infection. Early diagnosis leads to targeted therapy and subsequent partial improvement of the quality of life. This study also shows the first insights into sp. subtype distribution in humans in Slovakia.
Topics: Humans; Slovakia; Blastocystis; Male; Female; Middle Aged; Blastocystis Infections; Renal Dialysis; Aged; Polymerase Chain Reaction; Adult; Renal Insufficiency, Chronic; Feces; Intestinal Diseases, Parasitic; Aged, 80 and over
PubMed: 38940102
DOI: 10.26444/aaem/185634 -
Journal of Global Health Jun 2024Diarrhoeal disease disproportionately affects children <5 years in low- and middle-income countries (LMICs). The pathogens responsible for diarrhoea are commonly... (Meta-Analysis)
Meta-Analysis
Lifestraw Family water filters in low- and middle-income countries: a systematic review and meta-analysis to define longer-term public health impact against childhood diarrhoea and inform scale-up.
BACKGROUND
Diarrhoeal disease disproportionately affects children <5 years in low- and middle-income countries (LMICs). The pathogens responsible for diarrhoea are commonly transmitted through faecally-contaminated drinking water. Lifestraw Family point-of-use water filters have been the subject of intervention studies for over a decade and were the first filters evaluated by the World Health Organization in its water treatment evaluation scheme to provide comprehensive protection against many diarrhoea-causing pathogens. This systematic review aimed to: 1) report on aspects related to physical environment and implementation and 2) conduct an updated meta-analysis on Lifestraw Family filter effectiveness against childhood diarrhoea based on studies with ≥12 months of follow-up.
METHODS
We conducted a literature search in November 2022 using MEDLINE, Embase, Cochrane, and CINAHL databases. Inclusion criteria were: 1) RCTs, cluster-RCTs, quasi-experimental, or matched cohort studies on 2) Lifestraw Family 1.0 or 2.0 filters 3) conducted in LMICs 4) that evaluated filter effectiveness against diarrhoea in children <5 and 5) analysed ≥12 months of follow-up data on clinical effectiveness against diarrhoea and were 6) published from 2010 with 7) full-text availability in English. A modified Newcastle-Ottawa Scale was used to assess risk of bias. Relative risk (RR) and 95% confidence intervals (CIs) were extracted and analysed using a random-effects meta-analysis.
RESULTS
We included 6 studies in LMICs involving 4740 children <5. Of the four clinically-effective interventions, common characteristics were access to improved water sources (75%), the 2.0 version of the filter or the 1.0 version with additional water storage (100%), use of behaviour change theory, community engagement, and health messaging (75%), local filter repair-and-replace mechanisms (75%), and specially-trained local interventionists (100%). The meta-analysis showed a 30% reduction in diarrhoea risk in the intervention group (RR = 0.69; 95% CI = 0.52-0.91, P = 0.01).
CONCLUSIONS
Lifestraw Family water filters can be effective interventions to reduce diarrhoea in vulnerable paediatric populations for at least one year, though certain aspects related to physical environment and implementation may increase their public health impact. The findings of this study suggest considerations for scale-up that can be applied in settings in need of longer-term interim solutions until universal access to safe drinking water is achieved.
Topics: Humans; Diarrhea; Developing Countries; Water Purification; Public Health; Filtration; Child, Preschool; Drinking Water; Infant
PubMed: 38939952
DOI: 10.7189/jogh.14.04018 -
Frontiers in Public Health 2024Ticks and pathogens they carry seriously impact human and animal health, with some diseases like Lyme and Alpha-gal syndrome posing risks. Searching for health...
INTRODUCTION
Ticks and pathogens they carry seriously impact human and animal health, with some diseases like Lyme and Alpha-gal syndrome posing risks. Searching for health information online can change people's health and preventive behaviors, allowing them to face the tick risks. This study aimed to predict the potential risks of tickborne diseases by examining individuals' online search behavior.
METHODS
By scrutinizing the search trends across various geographical areas and timeframes within the United States, we determined outdoor activities associated with potential risks of tick-related diseases. Google Trends was used as the data collection and analysis tool due to its accessibility to big data on people's online searching behaviors. We interact with vast amounts of population search data and provide inferences between population behavior and health-related phenomena. Data were collected in the United States from April 2022 to March 2023, with some terms about outdoor activities and tick risks.
RESULTS AND DISCUSSION
Results highlighted the public's risk susceptibility and severity when participating in activities. Our results found that searches for terms related to tick risk were associated with the five-year average Lyme Disease incidence rates by state, reflecting the predictability of online health searching for tickborne disease risks. Geographically, the results revealed that the states with the highest relative search volumes for tick-related terms were predominantly located in the Eastern region. Periodically, terms can be found to have higher search records during summer. In addition, the results showed that terms related to outdoor activities, such as "corn maze," "hunting," "u-pick," and "park," have moderate associations with tick-related terms. This study provided recommendations for effective communication strategies to encourage the public's adoption of health-promoting behaviors. Displaying warnings in the online search results of individuals who are at high risk for tick exposure or collaborating with outdoor activity locations to disseminate physical preventive messages may help mitigate the risks associated with tickborne diseases.
Topics: Humans; Tick-Borne Diseases; United States; Animals; Search Engine; Internet; Lyme Disease; Ticks; Information Seeking Behavior
PubMed: 38939559
DOI: 10.3389/fpubh.2024.1410713