-
The Journal of Dermatological Treatment Dec 2024Cutaneous infection in epidermolysis bullosa (EB) can cause significant morbidity, mortality, and dangerous sequelae. This review article aims to delve into the known... (Review)
Review
Cutaneous infection in epidermolysis bullosa (EB) can cause significant morbidity, mortality, and dangerous sequelae. This review article aims to delve into the known epidemiology of EB, highlight the disease's primary causative agents and their antimicrobial resistance spectrum. A thorough literature search was conducted using Medline, EMBASE, JBI and PubMed to gather data on the microbial landscape of EB wounds. The focus was on identifying the most common bacteria associated with EB infections and assessing their antimicrobial resistance profiles. The analysis revealed that is the most frequently identified bacterium in EB wounds, with a notable prevalence of methicillin-resistant strains (MRSA). Specific studies on mupirocin resistance further indicated rising rates of mupirocin-resistant , with one study reporting rates as high as 16.07%. Additionally, high resistance to other antibiotics, such as levofloxacin and trimethoprim/sulfamethoxazole, was observed in MRSA isolates. The findings highlight the critical need for regular resistance surveillance and the prudent use of mupirocin to manage infections effectively in EB. The multi-drug resistant nature of pathogens in EB presents a significant challenge in treatment, highlighting the importance of antimicrobial stewardship. Ultimately, given the sparse literature and the rarity of large-scale studies, further longitudinal research on the antimicrobial resistance profile of bacteria isolated from EB wounds is essential.
Topics: Humans; Epidermolysis Bullosa; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Wound Infection; Mupirocin; Drug Resistance, Bacterial
PubMed: 38936964
DOI: 10.1080/09546634.2024.2370424 -
PLoS Neglected Tropical Diseases Jun 2024Usutu virus (USUV) is a zoonotic arbovirus infecting mainly wild birds. It is transmitted by ornithophilic mosquitoes, mainly of the genus Culex from birds to birds and...
Usutu virus (USUV) is a zoonotic arbovirus infecting mainly wild birds. It is transmitted by ornithophilic mosquitoes, mainly of the genus Culex from birds to birds and to several vertebrate dead-end hosts. Several USUV lineages, differing in their virulence have emerged in the last decade and now co-circulate in Europe, impacting human populations. However, their relative transmission and effects on their mosquito vectors is still not known. We thus compared the vector competence and survival of Culex pipiens mosquitoes experimentally infected with two distinct USUV lineages, EU2 and EU3, that are known to differ in their virulence and replication in vertebrate hosts. Infection rate was variable among blood feeding assays but variations between EU2 and EU3 lineages were consistent suggesting that Culex pipiens was equally susceptible to infection by both lineages. However, EU3 viral load increased with viral titer in the blood meal while EU2 viral load was high at all titers which suggest a greater replication of EU2 than EU3 in mosquito. While their relative transmission efficiencies are similar, at least at low blood meal titer, positive correlation between transmission and blood meal titer was observed for EU3 only. Contrary to published results in vertebrates, EU3 induced a higher mortality to mosquitoes (i.e. virulence) than EU2 whatever the blood meal titer. Therefore, we found evidence of lineage-specific differences in vectorial capacity and virulence to both the vector and vertebrate host which lead to balanced propagation of both viral lineages. These results highlight the need to decipher the interactions between vectors, vertebrate hosts, and the diversity of arbovirus lineages to fully understand transmission dynamics.
PubMed: 38935783
DOI: 10.1371/journal.pntd.0012295 -
PLoS Pathogens Jun 2024The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes...
The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation, including the importance of phosphorylation, remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals crucial for malaria parasite development.
PubMed: 38935780
DOI: 10.1371/journal.ppat.1012360 -
PLoS Neglected Tropical Diseases Jun 2024Plague, a zoonotic disease caused by Yersinia pestis, was responsible for 3 historical human pandemics that killed millions of people. It remains endemic in rodent... (Review)
Review
BACKGROUND
Plague, a zoonotic disease caused by Yersinia pestis, was responsible for 3 historical human pandemics that killed millions of people. It remains endemic in rodent populations in Africa, Asia, North America, and South America but human plague is rare in most of these locations. However, human plague is still highly prevalent in Madagascar, which typically records a significant part of all annual global cases. This has afforded an opportunity to study contemporary human plague in detail using various typing methods for Y. pestis.
AIM
This review aims to summarize the methods that have been used to type Y. pestis in Madagascar along with the major discoveries that have been made using these approaches.
METHODS
Pubmed and Google Scholar were used to search for the keywords: "typing Yersinia pestis Madagascar," "evolution Yersinia pestis Madagascar," and "diversity Yersinia pestis Madagascar." Eleven publications were relevant to our topic and further information was retrieved from references cited in those publications.
RESULTS
The history of Y. pestis typing in Madagascar can be divided in 2 periods: the pre-genomics and genomics eras. During the pre-genomics era, ribotyping, direct observation of plasmid content and plasmid restriction fragment length polymorphisms (RFLP) were employed but only revealed a limited amount of diversity among Malagasy Y. pestis strains. Extensive diversity only started to be revealed in the genomics era with the use of clustered regularly interspaced palindromic repeats (CRISPR), multiple-locus variable number tandem repeats (VNTR) analysis (MLVA), and single-nucleotide polymorphisms (SNPs) discovered from whole genome sequences. These higher-resolution genotyping methods have made it possible to highlight the distribution and persistence of genotypes in the different plague foci of Madagascar (Mahajanga and the Central and Northern Highlands) by genotyping strains from the same locations across years, to detect transfers between foci, to date the emergence of genotypes, and even to document the transmission of antimicrobial resistant (AMR) strains during a pneumonic plague outbreak. Despite these discoveries, there still remain topics that deserve to be explored, such as the contribution of horizontal gene transfer to the evolution of Malagasy Y. pestis strains and the evolutionary history of Y. pestis in Madagascar.
CONCLUSIONS
Genotyping of Y. pestis has yielded important insights on plague in Madagascar, particularly since the advent of whole-genome sequencing (WGS). These include a better understanding of plague persistence in the environment, antimicrobial AMR and multi-drug resistance in Y. pestis, and the person-to-person spread of pneumonic plague. Considering that human plague is still a significant public health threat in Madagascar, these insights can be useful for controlling and preventing human plague in Madagascar and elsewhere, and also are relevant for understanding the historical pandemics and the possible use of Y. pestis as a biological weapon.
Topics: Yersinia pestis; Madagascar; Plague; Humans; Animals; Genotype; Genotyping Techniques
PubMed: 38935608
DOI: 10.1371/journal.pntd.0012252 -
STAR Protocols Jun 2024The intestinal lamina propria (LP) is a leukocyte-rich cornerstone of the immune system owing to its vital role in immune surveillance and barrier defense against...
The intestinal lamina propria (LP) is a leukocyte-rich cornerstone of the immune system owing to its vital role in immune surveillance and barrier defense against external pathogens. Here, we present a protocol for isolating and analyzing immune cell subsets from the mouse intestinal LP for further downstream applications. Starting from tissue collection and cleaning, epithelium removal, and enzymatic digestion to collection of single cells, we explain each step in detail to maximize the yield of immune cells from the intestinal LP.
PubMed: 38935510
DOI: 10.1016/j.xpro.2024.103154 -
JAMA Network Open Jun 2024Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily...
IMPORTANCE
Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time.
OBJECTIVE
To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission.
EXPOSURES
Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal β-lactam agent use.
MAIN OUTCOMES AND MEASURES
Annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of β-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics.
RESULTS
Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal β-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal β-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.
Topics: Humans; Anti-Bacterial Agents; Cross-Sectional Studies; Sepsis; Male; Female; Middle Aged; Community-Acquired Infections; United States; Aged; Methicillin-Resistant Staphylococcus aureus; Adult; Hospitals
PubMed: 38935374
DOI: 10.1001/jamanetworkopen.2024.18923 -
Indian Journal of Public Health Oct 2023LAMP assay is widely used for detecting pathogens. We observed that the conventional and gradient polymerase chain reaction (PCR) could not detect the extracted...
Electrophoresis of Amplicons is a Better Method to Understand the Performance of Loop-mediated Isothermal Amplification Assay for Screening the Presence of Escherichia coli in Water.
LAMP assay is widely used for detecting pathogens. We observed that the conventional and gradient polymerase chain reaction (PCR) could not detect the extracted Escherichia coli DNA; real-time PCR was able to detect up to a certain limit (10-8 bacterial dilution). At the same time, the LAMP assay could detect the bacteria at a much lower concentration (10-14 dilution). The results of the LAMP assay were evaluated using agarose gel electrophoresis and DNA binding dye (PicoGreen), but only gel electrophoresis gave reliable results. Therefore, we propose using electrophoresis-based amplicon detection to overcome the limitations of dye-based detection. We believe that this amplicon detection will go a long way in the screening of potable drinking water.
Topics: Escherichia coli; Nucleic Acid Amplification Techniques; Water Microbiology; Real-Time Polymerase Chain Reaction; Humans; Electrophoresis, Agar Gel; DNA, Bacterial; Molecular Diagnostic Techniques; Drinking Water
PubMed: 38934812
DOI: 10.4103/ijph.ijph_1628_22 -
Annals of Human Biology Feb 2024Rising global obesity rates are linked with inflammation and associated morbidities. These negative outcomes are generally more common in low-resource communities within...
BACKGROUND
Rising global obesity rates are linked with inflammation and associated morbidities. These negative outcomes are generally more common in low-resource communities within high-income countries; however, it is unclear how frequent infectious disease exposures in these settings may influence the relationship between adiposity and inflammation.
AIM
We test associations between adiposity measures and distinct forms of inflammation among adults ( = 80) living in low-resource U.S. communities experiencing high levels of obesity and pathogen exposure.
SUBJECTS AND METHODS
Adiposity measures included BMI and percent body fat. Inflammation measures included systemic inflammation (C-reactive protein [CRP]) and localised intestinal inflammation (faecal calprotectin [FC]). The relationship between a condition characterised by elevated inflammation ( infection) and adiposity was also considered.
RESULTS
Adiposity was not significantly related to FC concentration. However, both adiposity measures were positively related with odds of CRP elevation and infection was associated with significantly lower adiposity measures (all < 0.05).
CONCLUSION
For this disadvantaged U.S. sample, the association between adiposity and inflammation varies by the systemic/localised nature of inflammation and the likely underlying cause of inflammation. Defining these associations will improve understanding of how rising obesity rates shape long-term health inequities, with implications for more effective intervention design.
Topics: Humans; Adiposity; Inflammation; Female; Male; Adult; Middle Aged; Chronic Disease; United States; C-Reactive Protein; Helicobacter Infections; Helicobacter pylori; Leukocyte L1 Antigen Complex; Obesity; Young Adult; Body Mass Index; Aged; Feces
PubMed: 38934696
DOI: 10.1080/03014460.2024.2368851 -
MSystems Jun 2024causes both hospital- and community-acquired infections in humans worldwide. Due to the high incidence of infection, is also one of the most sampled and sequenced...
UNLABELLED
causes both hospital- and community-acquired infections in humans worldwide. Due to the high incidence of infection, is also one of the most sampled and sequenced pathogens today, providing an outstanding resource to understand variation at the bacterial subspecies level. We processed and downsampled 83,383 public Illumina whole-genome shotgun sequences and 1,263 complete genomes to produce 7,954 representative substrains. Pairwise comparison of average nucleotide identity revealed a natural boundary of 99.5% that could be used to define 145 distinct strains within the species. We found that intermediate frequency genes in the pangenome (present in 10%-95% of genomes) could be divided into those closely linked to strain background ("strain-concentrated") and those highly variable within strains ("strain-diffuse"). Non-core genes had different patterns of chromosome location. Notably, strain-diffuse genes were associated with prophages; strain-concentrated genes were associated with the vSaβ genome island and rare genes (<10% frequency) concentrated near the origin of replication. Antibiotic resistance genes were enriched in the strain-diffuse class, while virulence genes were distributed between strain-diffuse, strain-concentrated, core, and rare classes. This study shows how different patterns of gene movement help create strains as distinct subspecies entities and provide insight into the diverse histories of important functions.
IMPORTANCE
We analyzed the genomic diversity of , a globally prevalent bacterial species that causes serious infections in humans. Our goal was to build a genetic picture of the different strains of and which genes may be associated with them. We reprocessed >84,000 genomes and subsampled to remove redundancy. We found that individual samples sharing >99.5% of their genome could be grouped into strains. We also showed that a portion of genes that are present in intermediate frequency in the species are strongly associated with some strains but completely absent from others, suggesting a role in strain specificity. This work lays the foundation for understanding individual gene histories of the species and also outlines strategies for processing large bacterial genomic data sets.
PubMed: 38934646
DOI: 10.1128/msystems.00143-24