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International Journal of Molecular... Mar 2024Anthracnose, induced by , poses a substantial economic threat to rubber tree yields and various other tropical crops. Ede1, an endocytic scaffolding protein, plays a...
Anthracnose, induced by , poses a substantial economic threat to rubber tree yields and various other tropical crops. Ede1, an endocytic scaffolding protein, plays a crucial role in endocytic site initiation and maturation in yeast. Metacaspases, sharing structural similarities with caspase family proteases, are essential for maintaining cell fitness. To enhance our understanding of the growth and virulence of , we identified a homologue of Ede1 (CgEde1) in . The knockout of led to impairments in vegetative growth, conidiation, and pathogenicity. Furthermore, we characterized a weakly interacted partner of CgEde1 and CgMca (orthologue of metacaspase). Notably, both the single mutant Δ and the double mutant Δ/Δ exhibited severe defects in conidiation and germination. Polarity establishment and pathogenicity were also disrupted in these mutants. Moreover, a significantly insoluble protein accumulation was observed in Δ and Δ/Δ strains. These findings elucidate the mechanism by which CgEde1 and CgMca regulates the growth and pathogenicity of . Their regulation involves influencing conidiation, polarity establishment, and maintaining cell fitness, providing valuable insights into the intricate interplay between CgEde1 and CgMca in .
Topics: Virulence; Fungal Proteins; Colletotrichum; Plant Diseases
PubMed: 38474190
DOI: 10.3390/ijms25052943 -
Virulence Dec 2023Intercellular communication among microbes plays an important role in disease exacerbation. Recent advances have described small vesicles, termed as "extracellular... (Review)
Review
Intercellular communication among microbes plays an important role in disease exacerbation. Recent advances have described small vesicles, termed as "extracellular vesicles" (EVs), previously disregarded as "cellular dust" to be vital in the intracellular and intercellular communication in host-microbe interactions. These signals have been known to initiate host damage and transfer of a variety of cargo including proteins, lipid particles, DNA, mRNA, and miRNAs. Microbial EVs, referred to generally as "membrane vesicles" (MVs), play a key role in disease exacerbation suggesting their importance in pathogenicity. Host EVs help coordinate antimicrobial responses and prime the immune cells for pathogen attack. Hence EVs with their central role in microbe-host communication, may serve as important diagnostic biomarkers of microbial pathogenesis. In this review, we summarize current research regarding the roles of EVs as markers of microbial pathogenesis with specific focus on their interaction with host immune defence and their potential as diagnostic biomarkers in disease conditions.
Topics: Humans; Extracellular Vesicles; MicroRNAs; Virulence; Mycoses; Biomarkers
PubMed: 36794396
DOI: 10.1080/21505594.2023.2180934 -
Viruses Nov 2023The porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic losses to the swine industry. The U.S., China, and Peru have reported...
Pathogenicity Studies of NADC34-like Porcine Reproductive and Respiratory Syndrome Virus LNSY-GY and NADC30-like Porcine Reproductive and Respiratory Syndrome Virus GXGG-8011 in Piglets.
The porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic losses to the swine industry. The U.S., China, and Peru have reported NADC30-like or NADC34-like PRRSV-infected piglets, which have been identified as the cause of a significant number of abortions in clinics. Although the pathogenicity of NADC30-like PRRSV and NADC34-like PRRSV in piglets exhibits significant variability globally, studies on their pathogenicity in China are limited. In this study, the animal experiments showed that within 8-14 days post-infection, both piglets infected with NADC30-like PRRSV GXGG-8011 and those infected with NADC34-like PRRSV LNSY-GY exhibited significant weight loss compared to the control piglets. Additionally, the viremia of the LNSY-GY persisted for 28 days, while the viremia of piglets infected with the GXGG-8011 lasted for 17 days. Similarly, the duration of viral shedding through the fecal-oral route after the LNSY-GY infection was longer than that observed after the GXGG-8011 infection. Furthermore, post-infection, both the LNSY-GY and GXGG-8011 led to pronounced histopathological lesions in the lungs of piglets, including interstitial pneumonia and notable viral colonization. However, the antibody production in the LNSY-GY-infected group occurred earlier than that in the GXGG-8011-infected group. Our research findings indicate that LNSY-GY is a mildly pathogenic strain in piglets, whereas we speculate that the GXGG-8011 might be a highly pathogenic strain.
Topics: Animals; Swine; Porcine respiratory and reproductive syndrome virus; Porcine Reproductive and Respiratory Syndrome; Virulence; Viremia; Genome, Viral; Phylogeny; China
PubMed: 38005924
DOI: 10.3390/v15112247 -
JCI Insight Jul 2023The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells....
The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells. Such cell-to-cell transfer could represent a target for counteracting microbial pathogenesis. However, our understanding of the underlying cellular and molecular processes remains woefully insufficient. Using intravital 2-photon microscopy of caspase-3 activation in the Leishmania major-infected (L. major-infected) live skin, we showed increased apoptosis in cells infected by the parasite. Also, transfer of the parasite to new host cells occurred directly without a detectable extracellular state and was associated with concomitant uptake of cellular material from the original host cell. These in vivo findings were fully recapitulated in infections of isolated human phagocytes. Furthermore, we observed that high pathogen proliferation increased cell death in infected cells, and long-term residency within an infected host cell was only possible for slowly proliferating parasites. Our results therefore suggest that L. major drives its own dissemination to new phagocytes by inducing host cell death in a proliferation-dependent manner.
Topics: Leishmania major; Phagocytes; Apoptosis; Humans; Virulence; Mice, Inbred C57BL; Cells, Cultured; Mice; Animals
PubMed: 37310793
DOI: 10.1172/jci.insight.169020 -
Virulence Dec 2024Animal models that can replicate clinical and pathologic features of severe human coronavirus infections have been instrumental in the development of novel vaccines and... (Review)
Review
Animal models that can replicate clinical and pathologic features of severe human coronavirus infections have been instrumental in the development of novel vaccines and therapeutics. The goal of this review is to summarize our current understanding of the pathogenesis of coronavirus disease 2019 (COVID-19) and the pathologic features that can be observed in several currently available animal models. Knowledge gained from studying these animal models of SARS-CoV-2 infection can help inform appropriate model selection for disease modelling as well as for vaccine and therapeutic developments.
Topics: Animals; Humans; COVID-19; Virulence; SARS-CoV-2; Disease Models, Animal
PubMed: 38362881
DOI: 10.1080/21505594.2024.2316438 -
Frontiers in Cellular and Infection... 2023is an important human pathogen that may cause severe invasive pneumococcal diseases (IPDs) in young children and the elderly. A comprehensive comparative whole-genome...
INTRODUCTION
is an important human pathogen that may cause severe invasive pneumococcal diseases (IPDs) in young children and the elderly. A comprehensive comparative whole-genome analysis of invasive and non-invasive serotype strains offers great insights that are applicable to vaccine development and disease control.
METHODS
In this study, 58 invasive (strains isolated from sterile sites) and 71 non-invasive (serotypes that have not been identified as invasive in our study) pneumococcal isolates were identified among the 756 pneumococcal isolates obtained from seven hospitals in Zhejiang, China (2010-2022). Serotyping, antimicrobial resistance tests, and genomic analyses were conducted to characterize these strains.
RESULTS AND DISCUSSION
The three most invasive serotypes were 23F, 14, and 6B. The invasive pneumococcal isolates' respective resistance rates against penicillin, ceftriaxone, tetracycline, and erythromycin were 34.5%, 15.5%, 98.3%, and 94.7%. Whole-genome sequencing indicated that the predominant invasive clonal complexes were CC271, CC876, and CC81. The high rate of penicillin non-susceptible (PNSP) is related to the clonal distribution of resistance-conferring penicillin-binding proteins (PBP). Interestingly, we found a negative correlation between invasiveness and resistance in the invasive pneumococcal serotype strains, which might be due to the proclivity of certain serotypes to retain their β-lactam resistance. Moreover, the mutually exclusive nature of and suggests their intricate and potentially redundant roles in promoting the development of IPD. These findings reveal significant implications for pneumococcal vaccine development in China, potentially informing treatment strategies and measures to mitigate disease transmission.
Topics: Child; Humans; Child, Preschool; Aged; Streptococcus pneumoniae; Virulence; Drug Resistance, Microbial; Penicillins; Pneumococcal Vaccines; Genomics
PubMed: 37928186
DOI: 10.3389/fcimb.2023.1238693 -
MSystems Aug 2023has become one of the most challenging pathogens in many countries with limited treatment options available. Cefiderocol, a novel siderophore-conjugated cephalosporin,...
has become one of the most challenging pathogens in many countries with limited treatment options available. Cefiderocol, a novel siderophore-conjugated cephalosporin, shows potent activity against , including isolates resistant to carbapenems. To date, few reports on the mechanisms of cefiderocol resistance are available. In order to investigate potential mechanisms of cefiderocol resistance in , we performed evolution experiments at sub-lethal concentrations of the antibiotic. All four cefiderocol-resistant strains obtained harbored mutations in two-component system BaeS-BaeR. When we engineered the mutations of BaeS (D89V) and BaeR (S104N) into the genome of ATCC 17978, these mutations increased cefiderocol minimum inhibitory concentrations (MICs) by 8-fold to 16-fold. Transcriptome analyses showed that the expression of MacAB-TolC and MFS transporters was up-regulated in BaeSR mutants. Strains over-expressing MFS transporter and MacAB-TolC displayed higher MICs and higher median inhibition concentration (IC) values, while MICs and IC decreased when efflux pump genes were knocked out. In a BaeR mutant with up-regulated operon, we observed a higher number of pili, enhanced surface motility, and increased biofilm formation compared to wild-type ATCC 17978. Using the infection model, we found that the BaeS mutant in which operon was up-regulated exhibited increased virulence. In conclusion, the mutations in BaeSR decreased cefiderocol susceptibility of through up-regulating efflux pumps gene expression. BaeS or BaeR also controls the expression of and , influencing biofilm formation, surface motility, and virulence in . IMPORTANCE The widespread prevalence of ulti-rugesistant (MDRAB) poses a significant therapeutic challenge. Cefiderocol is considered a promising antibiotic for the treatment of MDRAB infections. Therefore, it is necessary to study the potential resistance mechanisms of cefiderocol to delay the development of bacterial resistance. Here, we demonstrated that mutations in and reduced the susceptibility of to cefiderocol by up-regulating the expression of the MFS family efflux pump and MacAB-TolC efflux pump. We propose that BaeS mutants increase bacterial virulence by up-regulating the expression of the operon. This also reports the regulatory effect of BaeSR on operon for the first time. This study provides further insights into the role of BaeSR in developing cefiderocol resistance and virulence in .
Topics: Acinetobacter baumannii; Virulence; Anti-Bacterial Agents; Cephalosporins; Membrane Transport Proteins; Mutation; Cefiderocol
PubMed: 37345941
DOI: 10.1128/msystems.01291-22 -
Nature Communications Dec 2023Klebsiella pneumoniae has been classified into two types, classical K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP). cKP isolates are highly diverse and...
Klebsiella pneumoniae has been classified into two types, classical K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP). cKP isolates are highly diverse and important causes of nosocomial infections; they include globally disseminated antibiotic-resistant clones. hvKP isolates are sensitive to most antibiotics but are highly virulent, causing community-acquired infections in healthy individuals. The virulence phenotype of hvKP is associated with pathogenicity loci responsible for siderophore and hypermucoid capsule production. Recently, convergent strains of K. pneumoniae, which possess features of both cKP and hvKP, have emerged and are cause of much concern. Here, we screen the genomes of 2,608 multidrug-resistant K. pneumoniae isolates from the United States and identify 47 convergent isolates. We perform phenotypic and genomic characterization of 12 representative isolates. These 12 convergent isolates contain a variety of antimicrobial resistance plasmids and virulence plasmids. Most convergent isolates contain aerobactin biosynthesis genes and produce more siderophores than cKP isolates but not more capsule. Unexpectedly, only 1 of the 12 tested convergent isolates has a level of virulence consistent with hvKP isolates in a murine pneumonia model. These findings suggest that additional studies should be performed to clarify whether convergent strains are indeed more virulent than cKP in mouse and human infections.
Topics: Humans; Animals; Mice; Virulence; Klebsiella pneumoniae; Virulence Factors; Anti-Bacterial Agents; Plasmids; Siderophores
PubMed: 38042959
DOI: 10.1038/s41467-023-43802-1 -
Clinical Microbiology and Infection :... Nov 2023Urinary tract infections (UTIs) are primarily caused by uropathogenic Escherichia coli (UPEC). This study aims to elucidate the role of the virulence factor HlyF in the...
OBJECTIVES
Urinary tract infections (UTIs) are primarily caused by uropathogenic Escherichia coli (UPEC). This study aims to elucidate the role of the virulence factor HlyF in the epidemiology and pathophysiology of UTIs and investigate the dissemination of plasmids carrying the hlyF gene.
METHODS
An epidemiological analysis was conducted on a representative collection of 225 UPEC strains isolated from community-acquired infections. Selected hlyF+ strains were fully sequenced using a combination of Illumina and Nanopore technologies. To investigate the impact of HlyF, a murine model of UTI was utilized to compare clinical signs, bacterial loads in the bladder, kidney, and spleen, onset of bacteraemia, and inflammation through cytokine quantification among wild-type hlyF+ strains, isogenic mutants, and complemented mutants.
RESULTS
Our findings demonstrate that 20% of UPEC encode the HlyF protein. These hlyF+ UPEC strains exhibited enhanced virulence, frequently leading to pyelonephritis accompanied by bloodstream infections. Unlike typical UPEC strains, hlyF+ UPEC strains demonstrate a broader phylogroup distribution and possess a unique array of virulence factors and antimicrobial resistance genes, primarily carried by ColV-like plasmids. In the murine UTI model, expression of HlyF was linked to the UPECs' capacity to induce urosepsis and elicit an exacerbated inflammatory response, setting them apart from typical UPEC strains.
DISCUSSION
Overall, our results strongly support the notion that HlyF serves as a significant virulence factor for UPECs, and the dissemination of ColV-like plasmids encoding HlyF warrants further investigation.
Topics: Animals; Female; Humans; Mice; Community-Acquired Infections; Disease Models, Animal; Escherichia coli Infections; Escherichia coli Proteins; Plasmids; Urinary Tract Infections; Uropathogenic Escherichia coli; Virulence; Virulence Factors
PubMed: 37532127
DOI: 10.1016/j.cmi.2023.07.024 -
International Journal of Molecular... Aug 2023ATP synthase catalyzes the synthesis of ATP by consuming the proton electrochemical gradient, which is essential for maintaining the life activity of organisms. The...
ATP synthase catalyzes the synthesis of ATP by consuming the proton electrochemical gradient, which is essential for maintaining the life activity of organisms. The peripheral stalk belongs to ATP synthase and plays an important supporting role in the structure of ATP synthase, but their regulation in filamentous fungi are not yet known. Here, we characterized the subunits of the peripheral stalk, , , and , and explored their functions on development and pathogenicity of . The , , and deletion mutations (, , and ) presented deficiencies in vegetative growth, sporulation, and pathogenicity. The sensitivity of , , and to fludioxonil, phenamacril, pyraclostrobine, and fluazinam decreased. In addition, exhibited decreased sensitivity to ionic stress and osmotic stress, and and were more sensitive to oxidative stress. , , and were located on the mitochondria, and , , and disrupted mitochondrial location. Furthermore, we demonstrated the interaction among FfATPh, FfATP5, and FfATPb by Bimolecular Fluorescent Complimentary (BiFC) analysis. In conclusion, , , and participated in regulating development, pathogenicity, and sensitivity to fungicides and stress factors in .
Topics: Fungicides, Industrial; Virulence; Fusarium; Nitric Oxide Synthase; Adenosine Triphosphate
PubMed: 37686077
DOI: 10.3390/ijms241713273