The spread of multidrug-resistant Escherichia coli in healthcare facilities is a global challenge. Hospital-acquired infections produced by Escherichia coli include gastrointestinal, blood-borne, urinary tract, surgical sites, and neonatal infections. Therefore, novel approaches are needed to deal with this pathogen and its rising resistance. The concept of attenuating virulence factors is an alternative strategy that might lead to low levels of resistance and combat this pathogen. A sub-inhibitory concentration (1⁄4 MIC) of sitagliptin and nitazoxanide was used for phenotypic assessments of Escherichia coli virulence factors such as biofilm production, swimming motility, serum resistance, and protease production. Moreover, qRT-PCR was used to determine the impact of sub-MIC of the tested drugs on the relative expression levels of papC, fimH, fliC, kpsMTII, ompT_m, and stcE genes encoding virulence factors in Escherichia coli. Also, an in vivo model was conducted as a confirmatory test. Phenotypically, our findings demonstrated that the tested strains showed a significant decrease in all the tested virulence factors. Moreover, the genotypic results showed a significant downregulation in the relative expression levels of all the tested genes. Besides, the examined drugs were found to be effective in protecting mice against Escherichia coli pathogenesis. Sitagliptin and nitazoxanide exhibited strong anti-virulence activities against Escherichia coli. In addition, it is recommended that they might function as adjuvant in the management of Escherichia coli infections with either conventional antimicrobial agents or alone as alternative treatment measures.
- MeSH
- antibakteriální látky * farmakologie MeSH
- biofilmy účinky léků MeSH
- dusíkaté sloučeniny MeSH
- Escherichia coli * účinky léků patogenita genetika MeSH
- faktory virulence genetika metabolismus MeSH
- infekce vyvolané Escherichia coli * farmakoterapie mikrobiologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- mnohočetná bakteriální léková rezistence MeSH
- myši MeSH
- proteiny z Escherichia coli genetika MeSH
- sitagliptin fosfát * farmakologie MeSH
- thiazoly * farmakologie MeSH
- virulence účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Escherichia coli is a significant pathogen in extraintestinal infections, and ESBL-producing E. coli poses a major clinical challenge due to its antibiotic resistance. This study comprehensively analyzed E. coli isolates from urine and blood samples of patients with urinary tract and bloodstream infections at three major tertiary hospitals in South Korea. The goal was to provide insights into the distribution, antibiotic resistance, and virulence factors of these strains. Our analysis identified CTX-M and TEM as the dominant ESBL types, found in 71.7% and 61.7% of isolates, respectively, with 46.7% showing co-occurrence. Multilocus sequence typing (MLST) revealed the predominance of high-risk clones such as ST131, ST69, ST73, and ST95, with rare sequence types like ST410 and ST405 also identified. The high prevalence of virulence factors, including iutA (80.8%) and kpsMII (74.2%), further highlights the complexity of these strains. In addition, 38.3% of clinical isolates contained a combination of siderophore, adhesin, protectin, and toxin-related genes. There was no significant difference between urinary tract and bloodstream infections or regional differentiation in Korea. This study highlights the importance of controlling ESBL-producing E. coli infections, especially given the increasing incidence among patients with underlying medical conditions and older adults who are more susceptible to urinary tract infections. These findings serve as valuable indicators for pathogen analysis, especially those harboring antibiotic resistance and toxin genes. The insights gained are expected to contribute significantly to the development of infectious disease prevention and control strategies.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriemie * mikrobiologie epidemiologie MeSH
- beta-laktamasy * genetika metabolismus MeSH
- dospělí MeSH
- Escherichia coli * genetika izolace a purifikace patogenita enzymologie účinky léků klasifikace MeSH
- faktory virulence genetika MeSH
- infekce močového ústrojí * mikrobiologie epidemiologie MeSH
- infekce vyvolané Escherichia coli * mikrobiologie epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- mladý dospělý MeSH
- multilokusová sekvenční typizace MeSH
- prevalence MeSH
- proteiny z Escherichia coli genetika metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- virulence MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Korejská republika MeSH
The objective of this study was to characterize the virulence characteristics of a collection of Klebsiella pneumoniae isolates collected from different clinical sources. A collection of 60 non-repetitive K. pneumoniae isolates, was studied. In vitro, virulence was analyzed by testing the survival of bacteria in pooled human serum. Isolates were typed by MLST. The genomes of 23 K. pneumoniae isolates, representatives of different STs and virulence profiles, were completely sequenced using the Illumina platform. Of note, 26/60 of K. pneumoniae isolates were resistant to killing by complement. Serum-resistant isolates belonged to distinct STs. Analysis of WGS data with VFDB showed the presence of several virulence genes related various virulence functions. Specifically, serum-resistant isolates carried a higher number of ORFs, which were associated with serum resistance, compared to serum-sensitive isolates. Additionally, analysis of WGS data showed the presence of multiple plasmid replicons that could be involved with the spread and acquisition of resistance and virulence genes. In conclusion, analysis of virulence characteristics showed that an important percentage (31.6%) of K. pneumoniae isolates were in vitro virulent by exhibiting resistance to serum. Thus, the presence of several virulence factors, in combination with the presence of multidrug resistance, could challenge antimicrobial therapy of infections caused by such bacteria.
- MeSH
- faktory virulence * genetika MeSH
- genom bakteriální MeSH
- infekce bakteriemi rodu Klebsiella * mikrobiologie genetika MeSH
- Klebsiella pneumoniae * genetika patogenita izolace a purifikace MeSH
- lidé MeSH
- multilokusová sekvenční typizace MeSH
- nemocnice MeSH
- plazmidy genetika MeSH
- sekvenování celého genomu MeSH
- virulence genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Řecko MeSH
Klebsiella pneumoniae, a Gram-negative bacterium, comprises strains with diverse virulence potentials, ranging from classical to hypervirulent variants. Understanding the genetic basis underlying the virulence disparities between hypervirulent (hvKp) and classical K. pneumoniae (cKp) strains is crucial. hvKp strains are characterized by hypermucoviscosity, attributed to the presence of specific virulence genes and the production of molecules that aid in their ability to survive, evade host immune defenses, and cause infection. In contrast, classical strains exhibit a broader array of antimicrobial resistance determinants, conferring resistance to multiple antibiotics. Although current definitions of hvKp incorporate clinical features, phenotypes, and genotypes, identifying hvKp strains in clinical settings remains challenging. Genomic studies have been pivotal and have helped to identify distinct genetic profiles in hvKp strains, including unique virulence plasmids and chromosomal variations, underscoring the genetic diversity within K. pneumoniae populations. This review examines the virulence and genetic determinants associated with hvKp. The presence of genes defining hypervirulence, alongside considerations of their utility as biomarkers and targets for therapeutic strategies, is discussed, while also providing insight into biofilm formation by hvKp and key questions that need urgent responses in understanding hvKp.
- MeSH
- antibakteriální látky farmakologie MeSH
- biofilmy růst a vývoj MeSH
- faktory virulence * genetika MeSH
- infekce bakteriemi rodu Klebsiella * mikrobiologie MeSH
- Klebsiella pneumoniae * patogenita genetika účinky léků MeSH
- lidé MeSH
- virulence genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
UNLABELLED: The Aspergillus genus encompasses a diverse array of species, some of which are opportunistic pathogens. Traditionally, human aspergillosis has primarily been linked to a few Aspergillus species, predominantly A. fumigatus. Changes in epidemiology and advancements in molecular techniques have brought attention to less common and previously unrecognized pathogenic cryptic species. Despite the taxonomic recognition of many cryptic species in section Terrei, their virulence potential and clinical implications, compared to A. terreus sensu stricto, remain poorly understood. Hence, the current study utilized the alternative in vivo model Galleria mellonella to evaluate the virulence potential of 19 accepted Aspergillus species in section Terrei, classified into three series (major phylogenetic clades): Terrei, Nivei, and Ambigui. Analyzing the median survival rates of infected larvae of all species in each series revealed that series Ambigui has a significantly lower virulence compared to series Terrei and Nivei. Taking a closer look at series Terrei and Nivei revealed a trend of survival within each clade, dividing the species into two groups: highly virulent (up to 72 h survival) and less virulent (up to 144 h survival). Histological observation, considering fungal distribution and filamentation, further supported this assessment, revealing increased distribution and hyphal formation in virulent species. Additionally, the susceptibility profile of conventional antifungals was determined, revealing an increased azole minimum inhibitory concentration for some tested cryptic species such as A. niveus and A. iranicus. Our results highlight the importance of cryptic species identification, as they can exhibit different levels of virulence and show reduced antifungal susceptibility. IMPORTANCE: With changing fungal epidemiology and an increasingly vulnerable population, cryptic Aspergillus species are emerging as human pathogens. Their diversity and clinical relevance remain underexplored, with some species showing reduced antifungal susceptibility and higher virulence, highlighting the need for better preparedness in clinical practice. Using the Galleria mellonella model, we assessed the virulence of Aspergillus species of section Terrei, including cryptic and non-cryptic species, across three series Terrei, Nivei, and Ambigui. The results revealed significant virulence variation among the series, with some cryptic species displaying high virulence. Histological analysis confirmed increased hyphal formation and fungal spread in the more virulent species. Additionally, elevated azole minimum inhibitory concentrations were also observed in certain cryptic species. This study presents novel insights into the pathogenicity of Aspergillus section Terrei, emphasizing the critical importance of accurately identifying cryptic species due to their diverse virulence potential and antifungal resistance, which may have substantial clinical implications.
- MeSH
- antifungální látky farmakologie MeSH
- Aspergillus * patogenita klasifikace účinky léků genetika MeSH
- aspergilóza * mikrobiologie MeSH
- fylogeneze MeSH
- larva mikrobiologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- můry * mikrobiologie MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The ApxIVA protein belongs to a distinct class of a "clip and link" activity of Repeat-in-ToXin (RTX) exoproteins. Along with the three other pore-forming RTX toxins (ApxI, ApxII and ApxIII), ApxIVA serves as a major virulence factor of Actinobacillus pleuropneumoniae, the causative agent of porcine pneumonia. The gene encoding ApxIVA is located on a bicistronic operon downstream of the orf1 gene and is expressed exclusively under in vivo conditions. Both ApxIVA and ORF1 are essential for full virulence of A. pleuropneumoniae, but the molecular mechanisms by which they contribute to the pathogenicity are not yet understood. Here, we provide a comprehensive structural and functional analysis of ApxIVA and ORF1 proteins. Our findings reveal that the N-terminal segment of ApxIVA shares structural similarity with colicin M (ColM)-like bacteriocins and exhibits an antimicrobial activity. The ORF1 protein resembles the colicin M immunity protein (Cmi) and, like Cmi, is exported to the periplasm through its N-terminal signal peptide. Additionally, ORF1 can protect bacterial cells from the antimicrobial activity of ApxIVA, suggesting that ORF1 and ApxIVA function as an antibacterial toxin-immunity pair. Moreover, we demonstrate that fetal bovine serum could elicit ApxIVA and ORF1 production under in vitro conditions. These findings highlight the coordinated action of various RTX determinants, where the fine-tuned spatiotemporal production of ApxIVA may enhance the fitness of A. pleuropneumoniae, facilitating its invasion to a resident microbial community on the surface of airway mucosa.
- MeSH
- Actinobacillus pleuropneumoniae * genetika imunologie MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální proteiny * genetika metabolismus imunologie MeSH
- bakteriální toxiny genetika metabolismus imunologie MeSH
- faktory virulence genetika MeSH
- infekce bakteriemi rodu Actinobacillus mikrobiologie veterinární MeSH
- koliciny genetika metabolismus MeSH
- operon * MeSH
- prasata MeSH
- regulace genové exprese u bakterií MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- Bacteria patogenita MeSH
- houby patogenita MeSH
- imunita MeSH
- infekční nemoci * imunologie komplikace patologie MeSH
- lidé MeSH
- paraziti patogenita MeSH
- virulence MeSH
- viry patogenita MeSH
- zánět imunologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Environmental pollution is a serious problem that can cause sicknesses, fatality, and biological contaminants such as bacteria, which can trigger allergic reactions and infectious illnesses. There is also evidence that environmental pollutants can have an impact on the gut microbiome and contribute to the development of various mental health and metabolic disorders. This study aimed to study the antibiotic resistance and virulence potential of environmental Pseudomonas aeruginosa (P. aeruginosa) isolates in slaughterhouses. A total of 100 samples were collected from different slaughterhouse tools. The samples were identified by cultural and biochemical tests and confirmed by the VITEK 2 system. P. aeruginosa isolates were further confirmed by CHROMagarTM Pseudomonas and genetically by rpsL gene analysis. Molecular screening of virulence genes (fimH, papC, lasB, rhlI, lasI, csgA, toxA, and hly) and antibiotic resistance genes (blaCTX-M, blaAmpC, blaSHV, blaNDM, IMP-1, aac(6')-Ib-, ant(4')IIb, mexY, TEM, tetA, and qnrB) by PCR and testing the antibiotic sensitivity, biofilm formation, and production of pigments, and hemolysin were carried out in all isolated strains. A total of 62 isolates were identified as P. aeruginosa. All P. aeruginosa isolates were multidrug-resistant and most of them have multiple resistant genes. blaCTX-M gene was detected in all strains; 23 (37.1%) strains have the ability for biofilm formation, 33 strains had virulence genes, and 26 isolates from them have more than one virulence genes. There should be probably 60 (96.8%) P. aeruginosa strains that produce pyocyanin pigment. Slaughterhouse tools are sources for multidrug-resistant and virulent pathogenic microorganisms which are a serious health problem. Low-hygienic slaughterhouses could be a reservoir for resistance and virulence genes which could then be transferred to other pathogens.
- MeSH
- antibakteriální látky * farmakologie MeSH
- bakteriální léková rezistence genetika MeSH
- biofilmy účinky léků růst a vývoj MeSH
- faktory virulence * genetika MeSH
- jatka * MeSH
- mikrobiální testy citlivosti * MeSH
- mikrobiologie životního prostředí MeSH
- Pseudomonas aeruginosa * genetika účinky léků patogenita izolace a purifikace MeSH
- virulence genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Gram-positive bacteria are responsible for a wide range of infections in humans. In most Gram-positive bacteria, sortase A plays a significant role in attaching virulence factors to the bacteria's cell wall. These cell surface proteins play a significant role in virulence and pathogenesis. Even though antibiotics are available to treat these infections, there is a continuous search for an alternative strategy due to an increase in antibiotic resistance. Thus, using anti-sortase drugs to combat these bacterial infections may be a promising approach. Here, we describe a method for targeting Gram-positive bacterial infection by combining curcumin and trans-chalcone as sortase A inhibitors. We have used curcumin and trans-chalcone alone and in combination as a sortase A inhibitor. We have seen ~78%, ~43%, and ~94% inhibition when treated with curcumin, trans-chalcone, and a combination of both compounds, respectively. The compounds have also shown a significant effect on biofilm formation, IgG binding, protein A recruitment, and IgG deposition. We discovered that combining curcumin and trans-chalcone is more effective against Gram-positive bacteria than either compound alone. The present work demonstrated that a combination of these natural compounds could be used as an antivirulence therapy against Gram-positive bacterial infection.
- MeSH
- aminoacyltransferasy * antagonisté a inhibitory metabolismus MeSH
- antibakteriální látky * farmakologie chemie MeSH
- bakteriální proteiny * metabolismus antagonisté a inhibitory MeSH
- biofilmy * účinky léků MeSH
- chalkon * farmakologie chemie MeSH
- cysteinové endopeptidasy * metabolismus MeSH
- faktory virulence metabolismus MeSH
- grampozitivní bakteriální infekce farmakoterapie mikrobiologie MeSH
- grampozitivní bakterie účinky léků MeSH
- kurkumin * farmakologie chemie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- virulence účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Schistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins-from Liberia, Belo Horizonte and Puerto Rico. We demonstrated significant variation in virulence and host-parasite interactions. METHODS: We investigated the phenotypic characteristics of the parasite and its eggs, as well as the immunopathologic effects on laboratory mouse organ systems. RESULTS: Our results show significant differences in worm morphology, worm burden, egg size, and pathologic organ changes between these strains. The Puerto Rican strain showed the highest virulence, as evidenced by marked liver and spleen changes and advanced liver fibrosis indicated by increased collagen content. In contrast, the strains from Liberia and Belo Horizonte had a less pathogenic profile with less liver fibrosis. We found further variations in granuloma formation, cytokine expression and T-cell dynamics, indicating different immune responses. CONCLUSION: Our study emphasizes the importance of considering intra-specific variations of S. mansoni for the development of targeted therapies and public health strategies. The different virulence patterns, host immune responses and organ pathologies observed in these strains provide important insights for future research and could inform region-specific interventions for schistosomiasis control.
- MeSH
- cytokiny metabolismus MeSH
- interakce hostitele a parazita MeSH
- játra * parazitologie patologie MeSH
- myši MeSH
- Schistosoma mansoni * patogenita genetika imunologie MeSH
- schistosomiasis mansoni * parazitologie imunologie patologie MeSH
- slezina parazitologie patologie imunologie MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Libérie MeSH
- Portoriko MeSH
