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Journal of Natural Products Nov 2023Through genome mining efforts, two lasso peptide biosynthetic gene clusters (BGCs) within two different species of , a genus that contains pathogenic organisms that can...
Through genome mining efforts, two lasso peptide biosynthetic gene clusters (BGCs) within two different species of , a genus that contains pathogenic organisms that can infect patients with cystic fibrosis, were discovered. Using gene-refactored BGCs in , these lasso peptides, which were named achromonodin-1 and achromonodin-2, were heterologously expressed. Achromonodin-1 is naturally encoded by certain isolates from the sputum of patients with cystic fibrosis. The NMR structure of achromonodin-1 was determined, demonstrating that it is a threaded lasso peptide with a large loop and short tail structure, reminiscent of previously characterized lasso peptides that inhibit RNA polymerase (RNAP). Achromonodin-1 inhibits RNAP and has potent, focused activity toward , another isolate from the sputum of a cystic fibrosis patient. These efforts expand the repertoire of antimicrobial lasso peptides and provide insights into how isolates from certain ecological niches interact with each other.
Topics: Humans; Escherichia coli; Cystic Fibrosis; Peptides; Antimicrobial Peptides; Achromobacter; DNA-Directed RNA Polymerases
PubMed: 37870195
DOI: 10.1021/acs.jnatprod.3c00536 -
Emerging Microbes & Infections Dec 2023, the causative agent of whooping cough, is an extracellular, strictly human pathogen. However, it has been shown that cells can escape phagocytic killing and survive...
, the causative agent of whooping cough, is an extracellular, strictly human pathogen. However, it has been shown that cells can escape phagocytic killing and survive in macrophages upon internalization. Our time-resolved RNA-seq data suggest that efficiently adapts to the intramacrophage environment and responds to host bactericidal activities. We show that this adaptive response is multifaceted and, surprisingly, related to the BvgAS two-component system, a master regulator of virulence. Our results show that the expression of this regulatory circuit is downregulated upon internalization. Moreover, we demonstrate that the switch to the avirulent Bvg phase augments a very complex process based on the adjustment of central and energy metabolism, cell wall reinforcement, maintenance of appropriate redox and metal homeostasis, and repair of damaged macromolecules. Nevertheless, not all observed effects could be simply attributed to the transition to Bvg phase, suggesting that additional regulators are involved in the adaptation to the intramacrophage environment. Interestingly, a large number of genes required for the metabolism of sulphur were strongly modulated within macrophages. In particular, the mutant lacking two genes encoding cysteine dioxygenases displayed strongly attenuated cytotoxicity toward THP-1 cells. Collectively, our results suggest that intracellular cells have adopted the Bvg mode to acclimate to the intramacrophage environment and respond to antimicrobial activities elicited by THP-1 cells. Therefore, we hypothesize that the avirulent phase represents an authentic phenotype of internalized cells.
Topics: Humans; Bordetella pertussis; Whooping Cough; Bacterial Proteins; Phenotype; Macrophages; Gene Expression Regulation, Bacterial
PubMed: 36357372
DOI: 10.1080/22221751.2022.2146536 -
Frontiers in Cellular and Infection... 2023The efficacy of the adaptive immune system in the middle ear (ME) is well established, but the mechanisms are not as well defined as those of gastrointestinal or...
The efficacy of the adaptive immune system in the middle ear (ME) is well established, but the mechanisms are not as well defined as those of gastrointestinal or respiratory tracts. While cellular elements of the adaptive response have been detected in the MEs following infections (or intranasal immunizations), their specific contributions to protecting the organ against reinfections are unknown. How immune protection mechanisms of the MEs compares with those in the adjacent and attached upper and lower respiratory airways remains unclear. To address these knowledge gaps, we used an established mouse respiratory infection model that we recently showed also involves ME infections. delivered to the external nares of mice in tiny numbers very efficiently infects the respiratory tract and ascends the Eustachian tube to colonize and infect the MEs, where it causes severe but acute inflammation resembling human acute otitis media (AOM). Since this AOM naturally resolves, we here examine the immunological mechanisms that clear infection and protect against subsequent infection, to guide efforts to induce protective immunity in the ME. Our results show that once the MEs are cleared of a primary infection, the convalescent organ is strongly protected from reinfection by the pathogen despite its persistence in the upper respiratory tract, suggesting important immunological differences in these adjacent and connected organs. CD4+ and CD8+ T cells trafficked to the MEs following infection and were necessary to robustly protect against secondary challenge. Intranasal vaccination with heat killed conferred robust protection against infection to the MEs, even though the nasopharynx itself was only partially protected. These data establish the MEs as discrete effector sites of adaptive immunity and shows that effective protection in the MEs and the respiratory tract is significantly different. This model system allows the dissection of immunological mechanisms that can prevent bacteria in the nasopharynx from ascending the ET to colonize the ME.
Topics: Humans; Animals; Mice; Bordetella Infections; Respiratory System; Respiratory Tract Infections; Bordetella bronchiseptica; Otitis Media; Ear, Middle
PubMed: 38125908
DOI: 10.3389/fcimb.2023.1288057 -
Frontiers in Microbiology 2023Aquatic wildlife health assessment is critically important for aquatic wildlife conservation. However, the health assessment of aquatic wildlife (especially aquatic wild...
Aquatic wildlife health assessment is critically important for aquatic wildlife conservation. However, the health assessment of aquatic wildlife (especially aquatic wild animals) is difficult and often accompanied by invasive survey activities and delayed observability. As there is growing evidence that aquatic environmental microbiota could impact the health status of aquatic animals by influencing their symbiotic microbiota, we propose a non-invasive method to monitor the health status of wild aquatic animals using the environmental microbiota health index (microHI). However, it is unknown whether this method is effective for different ecotype groups of aquatic wild animals. To answer this question, we took a case study in the middle Yangtze River and studied the water environmental microbiota and fish gut microbiota at the fish community level, population level, and ecotype level. The results showed that the gut microHI of the healthy group was higher than that of the unhealthy group at the community and population levels, and the overall gut microHI was positively correlated with the water environmental microHI, whereas the baseline gut microHI was species-specific. Integrating these variations in four ecotype groups (filter-feeding, scraper-feeding, omnivorous, and carnivorous), only the gut microHI of the carnivorous group positively correlated with water environmental microHI. Alcaligenaceae, Enterobacteriaceae, and Achromobacter were the most abundant groups with health-negative-impacting phenotypes, had high positive correlations between gut sample group and environment sample group, and had significantly higher abundance in unhealthy groups than in healthy groups of carnivorous, filter-feeding, and scraper-feeding ecotypes. Therefore, using water environmental microHI to indicate the health status of wild fish is effective at the community level, is effective just for carnivorous fish at the ecotype level. In the middle Yangtze River, Alcaligenaceae, Enterobacteriaceae (family level), and (genus level) were the key water environmental microbial groups that potentially impacted wild fish health status. Of course, more data and research that test the current hypothesis and conclusion are encouraged.
PubMed: 38274749
DOI: 10.3389/fmicb.2023.1293342 -
Bordetella spp. block eosinophil recruitment to suppress the generation of early mucosal protection.Cell Reports Nov 2023Bordetella spp. are respiratory pathogens equipped with immune evasion mechanisms. We previously characterized a Bordetella bronchiseptica mutant (RB50ΔbtrS) that fails...
Bordetella spp. are respiratory pathogens equipped with immune evasion mechanisms. We previously characterized a Bordetella bronchiseptica mutant (RB50ΔbtrS) that fails to suppress host responses, leading to rapid clearance and long-lasting immunity against reinfection. This work revealed eosinophils as an exclusive requirement for RB50ΔbtrS clearance. We also show that RB50ΔbtrS promotes eosinophil-mediated B/T cell recruitment and inducible bronchus-associated lymphoid tissue (iBALT) formation, with eosinophils being present throughout iBALT for Th17 and immunoglobulin A (IgA) responses. Finally, we provide evidence that XCL1 is critical for iBALT formation but not maintenance, proposing a novel role for eosinophils as facilitators of adaptive immunity against B. bronchiseptica. RB50ΔbtrS being incapable of suppressing eosinophil effector functions illuminates active, bacterial targeting of eosinophils to achieve successful persistence and reinfection. Overall, our discoveries contribute to understanding cellular mechanisms for use in future vaccines and therapies against Bordetella spp. and extension to other mucosal pathogens.
Topics: Humans; Bordetella; Eosinophils; Bordetella Infections; Reinfection; Bordetella bronchiseptica
PubMed: 37883230
DOI: 10.1016/j.celrep.2023.113294 -
Aging Apr 2024In the past, some observational studies have highlighted the correlation between gut microbiota and irritable bowel syndrome (IBS). However, it is still unknown if the...
BACKGROUND
In the past, some observational studies have highlighted the correlation between gut microbiota and irritable bowel syndrome (IBS). However, it is still unknown if the composition of gut microbiota shows a causal effect on the risk of IBS.
AIM
To conduct Mendelian randomization (MR) analysis of the samples to study the probable causal relationship between the gut microbiota, their taxonomic groups, and the risk of IBS.
MATERIALS AND METHODS
In this study, the summarized data regarding 211 gut microbiota and their IBS genome-wide association studies (GWAS) were collected from public databases. The causal estimates were determined using five MR techniques, where Inverse Variance Weighted (IVW) regression was employed as the major MR technique. Herein, MR-PRESSO and MR-Egger intercept tests were conducted to prevent horizontal pleiotropy. Cochran's test was used to evaluate heterogeneity using the IVW and MR-Egger techniques.
RESULTS
IVW results showed that gut microbes, belonging to Class ( = 0.04; OR = 1.45), Family XIII ( = 0.03; OR = 1.34), Family ( = 0.003; OR =1.24), and UCG004 ( = 0.049; OR = 1.19) increased the risk of IBS, while ( = 0.03; OR = 0.83, 95% CI: 0.69-0.98) and ( = 0.02; OR = 0.86, 95% CI: 0.76-0.98) decreased the risk of IBS.
CONCLUSIONS
This study presented novel insights that highlighted the causal relationship between gut microbiota and IBS, and offered new treatment strategies for preventing or treating IBS.
Topics: Gastrointestinal Microbiome; Mendelian Randomization Analysis; Irritable Bowel Syndrome; Humans; Genome-Wide Association Study; Risk Factors
PubMed: 38669090
DOI: 10.18632/aging.205771 -
PloS One 2024The resurgence of pertussis has occurred around the world. However, the epidemiological profiles of pertussis cannot be well understood by current diseases surveillance....
PURPOSE
The resurgence of pertussis has occurred around the world. However, the epidemiological profiles of pertussis cannot be well understood by current diseases surveillance. This study was designed to understand the seroepidemiological characteristics of pertussis infection in the general population of Huzhou City, evaluate the prevalence infection of pertussis in the population, and offer insights to inform adjustments in pertussis prevention and control strategies.
METHODS
From September to October 2023, a cross-sectional serosurvey was conducted in Huzhou City, involving 1015 permanent residents. Serum samples were collected from the study subjects, and pertussis toxin IgG antibodies (Anti-PT-IgG) were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The analysis included the geometric mean concentration (GMC) of Anti-PT-IgG, rates of GMC≥40IU/mL, ≥100IU/mL, and <5IU/mL. Stratified comparisons were made based on age, vaccination history, and human categories.
RESULTS
Among the 1015 surveyed individuals, the geometric mean concentration (GMC) of Anti-PT-IgG was 10.52 (95% CI: 9.96-11.11) IU/mL, with a recent infection rate of 1.58%, a serum positivity rate of 11.43%, and a proportion with <5IU/mL of 40.49%. Among 357 children with clear vaccination history, susceptibility decreased with an increasing number of vaccine doses (Z = -6.793, P < 0.001). The concentration of Anti-PT-IgG exhibited a significant post-vaccination decline over time (Z = -5.143, P < 0.001). In women of childbearing age, the GMC of Anti-PT-IgG was 7.71 (95% CI: 6.90-8.62) IU/mL, with no significant difference in susceptibility among different age groups (χ2 = 0.545, P = 0.909). The annual pertussis infection rate in individuals aged ≥3 years was 9321 (95%CI: 3336-16039) per 100,000, with peak infection rates in the 20-29, 40-49, and 5-9 age groups at 34363 (95%CI: 6327-66918) per 100,000, 22307.72 (95%CI: 1380-47442) per 100,000, and 18020(95%CI: 1093-37266) per 100,000, respectively.
CONCLUSIONS
In 2023, the actual pertussis infection rate in the population of Huzhou City was relatively high. Vaccine-induced antibodies exhibit a rapid decay, and the estimated serum infection rate increases rapidly from post-school age, peaking in the 20-29 age group. It is recommended to enhance pertussis monitoring in adolescents and adults and refine vaccine immunization strategies.
Topics: Humans; Whooping Cough; Female; Cross-Sectional Studies; Adult; Male; China; Seroepidemiologic Studies; Child; Middle Aged; Adolescent; Child, Preschool; Young Adult; Infant; Immunoglobulin G; Antibodies, Bacterial; Aged; Pertussis Toxin; Prevalence; Pertussis Vaccine; Vaccination; Bordetella pertussis
PubMed: 38768133
DOI: 10.1371/journal.pone.0303508 -
Veterinary Microbiology Oct 2023In Finland, Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM), was first detected in 1992. The aim of this study was to genotype Finnish...
In Finland, Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM), was first detected in 1992. The aim of this study was to genotype Finnish T. equigenitalis isolates to investigate the epidemiology of the infection in the Finnish horse population. A total of 34 T. equigenitalis isolates from 24 horses obtained during 1992-2021 were subjected to whole genome sequencing (WGS) and subsequent local ad hoc core genome multi-locus sequence typing (cgMLST) targeting 1259 loci. Classical MLST profiles were extracted from the whole-genome sequence data. Three novel MLST types, ST81, ST82 and ST83, and four previously described sequence types, ST16, ST17, ST50 and ST63 were detected among the isolates. cgMLST minimum spanning tree analysis using 12 allele difference as threshold, resulted in five clusters and three singletons. cgMLST clusters were congruent with the MLST-defined groups, except for the ST83 isolates which were divided into two clusters. However, the high discriminatory power cgMLST allowed differentiation between isolates of the same MLST type as each isolate had a unique core genome ST. Our study suggests that cgMLST has the prospective for being a standardised typing method for T. equigenitalis in the future, and further contributes to worldwide phylogenetic and spatio-temporal analyses needed to better understand the epidemiology of the bacterium.
Topics: Horses; Animals; Taylorella equigenitalis; Multilocus Sequence Typing; Finland; Phylogeny; Prospective Studies; Gram-Negative Bacterial Infections; Horse Diseases; Genome, Bacterial
PubMed: 37633060
DOI: 10.1016/j.vetmic.2023.109853 -
Microbiology Spectrum Aug 2023is a genus of Gram-negative rods, which can cause persistent airway infections in people with cystic fibrosis (CF). The knowledge about virulence and clinical...
is a genus of Gram-negative rods, which can cause persistent airway infections in people with cystic fibrosis (CF). The knowledge about virulence and clinical implications of is still limited, and it is not fully established whether infections contribute to disease progression or if it is a marker of poor lung function. The most commonly reported species in CF is A. xylosoxidans. While other spp. are also identified in CF airways, the currently used Matrix-Assisted Laser Desorption/Ionization Time Of Flight Mass Spectrometry (MALDI-TOF MS) method in routine diagnostics cannot distinguish between species. Differences in virulence between species have consequently not been well studied. In this study, we compare phenotypes and proinflammatory properties of A. xylosoxidans, , , and using models. Bacterial supernatants were used to stimulate CF bronchial epithelial cells and whole blood from healthy individuals. Supernatants from the well-characterized CF-pathogen Pseudomonas aeruginosa were included for comparison. Inflammatory mediators were analyzed with ELISA and leukocyte activation was assessed using flow cytometry. The four species differed in morphology seen in scanning electron microscopy (SEM), but there were no observed differences in swimming motility or biofilm formation. Exoproducts from all species except caused significant IL-6 and IL-8 secretion from CF lung epithelium. The cytokine release was equivalent or stronger than the response induced by P. aeruginosa. All species activated neutrophils and monocytes in a lipopolysaccharide (LPS)-independent manner. Our results indicate that exoproducts of the four included species do not differ consistently in causing inflammatory responses, but they are equally or even more capable of inducing inflammation compared with the classical CF pathogen P. aeruginosa. Achromobacter xylosoxidans is an emerging pathogen among people with cystic fibrosis (CF). Current routine diagnostic methods are often unable to distinguish A. xylosoxidans from other species, and the clinical relevance of different species is still unknown. In this work, we show that four different species relevant to CF evoke similar inflammatory responses from airway epithelium and leukocytes , but they are all equally or even more proinflammatory compared to the classic CF-pathogen Pseudomonas aeruginosa. The results suggest that species are important airway pathogens in CF, and that all species are relevant to treat.
Topics: Humans; Achromobacter; Cystic Fibrosis; Gram-Negative Bacterial Infections; Achromobacter denitrificans; Lung
PubMed: 37284754
DOI: 10.1128/spectrum.00195-23 -
Journal of Hazardous Materials Jul 2024Spent mushroom substrate (SMS) holds valuable microbiota that can be useful in remediating polluted soils with hydrocarbons. However, the microorganisms behind the...
Spent mushroom substrate (SMS) holds valuable microbiota that can be useful in remediating polluted soils with hydrocarbons. However, the microorganisms behind the bioremediation process remain uncertain. In this work, a bioremediation assay of total petroleum hydrocarbons (TPHs) polluted soil by SMS application was performed to elucidate the microorganisms and consortia involved in biodegradation by a metabarcoding analysis. Untreated polluted soil was compared to seven bioremediation treatments by adding SMS of Agaricus bisporus, Pleurotus eryngii, Pleurotus ostreatus, and combinations. Soil microbial activity, TPH biodegradation, taxonomic classification, and predictive functional analysis were evaluated in the microbiopiles at 60 days. Different metagenomics approaches were performed to understand the impact of each SMS on native soil microbiota and TPHs biodegradation. All SMSs enhanced the degradation of aliphatic and aromatic hydrocarbons, being A. bisporus the most effective, promoting an efficient consortium constituted by the bacterial families Alcanivoraceae, Alcaligenaceae, and Dietziaceae along with the fungal genera Scedosporium and Aspergillus. The predictive 16 S rRNA gene study partially explained the decontamination efficacy by observing changes in the taxonomic structure of bacteria and fungi, and changes in the potential profiles of estimated degradative genes across the different treatments. This work provides new insights into TPHs bioremediation.
Topics: Biodegradation, Environmental; Soil Pollutants; Hydrocarbons; Soil Microbiology; Petroleum; Bacteria; Agaricus; Fungi; Pleurotus; Agaricales; RNA, Ribosomal, 16S
PubMed: 38776816
DOI: 10.1016/j.jhazmat.2024.134650