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Frontiers in Cellular and Infection... 2024species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic...
species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six -substituted phthalimides against three species. Of the derivatives, -butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10-50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive and . NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic , , , and , along with the polymicrobial biofilms of and . NBP markedly inhibited the hyphal formation and cell aggregation of and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., , , and , upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various strains.
Topics: Biofilms; Antifungal Agents; Phthalimides; Microbial Sensitivity Tests; Candida albicans; Hyphae; Candida; Candidiasis; Animals; Humans; Candida parapsilosis; Fungal Proteins; Fluconazole
PubMed: 38903941
DOI: 10.3389/fcimb.2024.1414618 -
BMC Microbiology Jun 2024In Addis Ababa, Ethiopia, open ditches along innner roads in residential areas serve to convey domestic wastewater and rainwater away from residences. Contamination of...
BACKGROUND
In Addis Ababa, Ethiopia, open ditches along innner roads in residential areas serve to convey domestic wastewater and rainwater away from residences. Contamination of drinking water by wastewater through faulty distribution lines could expose households to waterborne illnesses. This prompted the study to assess the microbiological safety of wastewater and drinking water in Addis Ababa, identify the pathogens therein, and determine their antibiotic resistance patterns.
RESULTS VIBRIO CHOLERAE
O1, mainly Hikojima serotype, was isolated from 23 wastewater and 16 drinking water samples. Similarly, 19 wastewater and 10 drinking water samples yielded Escherichia coli O157:H7. V. cholerae O1 were 100% resistant to the penicillins (Amoxacillin and Ampicillin), and 51-82% were resistant to the cephalosporins. About 44% of the V. cholerae O1 isolates in this study were Extended Spectrum Beta-Lactamase (ESBL) producers. Moreover, 26% were resistant to Meropenem. Peperacillin/Tazobactam was the only effective β-lactam antibiotic against V. cholerae O1. V. cholerae O1 isolates showed 37 different patterns of multiple resistance ranging from a minimum of three to a maximum of ten antimicrobials. Of the E. coli O157:H7 isolates, 71% were ESBL producers. About 96% were resistant to Ampicillin. Amikacin and Gentamicin were very effective against E. coli O157:H7 isolates. The isolates from wastewater and drinking water showed multiple antibiotic resistance against three to eight antibiotic drugs.
CONCLUSIONS
Open ditches for wastewater conveyance along innner roads in residence areas and underground faulty municipal water distribution lines could be possible sources for V. cholerae O1 and E. coli O157:H7 infections to surrounding households and for dissemination of multiple drug resistance in humans and, potentially, the environment.
Topics: Ethiopia; Vibrio cholerae O1; Wastewater; Escherichia coli O157; Anti-Bacterial Agents; Drinking Water; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; beta-Lactamases; Humans; Water Microbiology
PubMed: 38902619
DOI: 10.1186/s12866-024-03302-8 -
International Journal of Molecular... May 2024Diarrhoea remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The...
Diarrhoea remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diarrhoeic infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of plant-based compounds) was evaluated in vitro against selected diarrhoeic bacteria (, , , , , and ). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combination of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against at a FICI value of 0.086. The combinations of the agents tested in this study can thus be used for the development of new anti-diarrhoeic medications. However, studies focusing on their in vivo anti-diarrhoeic activity and safety are required before any consideration for utilization in human medicine.
Topics: Drug Synergism; Tetracycline; Anti-Bacterial Agents; Microbial Sensitivity Tests; Alkaloids; Bacteria; Diarrhea; Humans; Pyridines; Nitroquinolines; Organometallic Compounds
PubMed: 38892226
DOI: 10.3390/ijms25116038 -
International Journal of Molecular... May 2024is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and...
is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and food safety worldwide. The arginine deiminase (ADI) pathway plays an important role in bacterial environmental adaptation and pathogenicity. However, the biological functions and regulatory mechanisms of the pathway in remain unclear. In this study, we demonstrate that L-arginine upregulates the expression of the ADI gene cluster and promotes the growth of . The ADI gene cluster, which we proved to be comprised of two operons, and , significantly enhances the survival of in acidic environments both in vitro (in culture medium and in macrophage) and in vivo (in mice). The mRNA level and reporter gene fusion analyses revealed that ArgR, a transcriptional factor, is necessary for the activation of both and transcriptions. Bioinformatic analysis predicted the existence of multiple potential ArgR binding sites at the and promoter regions that were further confirmed by electrophoretic mobility shift assay, DNase I footprinting, or point mutation analyses. Together, our study provides insights into the important role of the ArgR-ADI pathway in the survival of under acidic conditions and the detailed molecular mechanism. These findings will deepen our understanding of how environmental changes and gene expression interact to facilitate bacterial adaptations and virulence.
Topics: Animals; Gene Expression Regulation, Bacterial; Bacterial Proteins; Mice; Hydrolases; Promoter Regions, Genetic; Operon; Repressor Proteins; Vibrio; Arginine; Multigene Family; Virulence; Microbial Viability
PubMed: 38891866
DOI: 10.3390/ijms25115679 -
Animals : An Open Access Journal From... Jun 2024Over the years, oysters have faced recurring mass mortality issues during the summer breeding season, with infection emerging as a significant contributing factor....
Over the years, oysters have faced recurring mass mortality issues during the summer breeding season, with infection emerging as a significant contributing factor. Tubules of gill filaments were confirmed to be in the hematopoietic position in , which produce hemocytes with immune defense capabilities. Additionally, the epithelial cells of oyster gills produce immune effectors to defend against pathogens. In light of this, we performed a transcriptome analysis of gill tissues obtained from infected with for 12 h and 48 h. Through this analysis, we identified 1024 differentially expressed genes (DEGs) at 12 h post-injection and 1079 DEGs at 48 h post-injection. Enrichment analysis of these DEGs revealed a significant association with immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. To further investigate the immune response, we constructed a protein-protein interaction (PPI) network using the DEGs enriched in immune-associated KEGG pathways. This network provided insights into the interactions and relationships among these genes, shedding light on the underlying mechanisms of the innate immune defense mechanism in oyster gills. To ensure the accuracy of our findings, we validated 16 key genes using quantitative RT-PCR. Overall, this study represents the first exploration of the innate immune defense mechanism in oyster gills using a PPI network approach. The findings provide valuable insights for future research on oyster pathogen control and the development of oysters with enhanced antimicrobial resistance.
PubMed: 38891754
DOI: 10.3390/ani14111707 -
Foods (Basel, Switzerland) May 2024can cause acute gastroenteritis, wound infections, and septicemia in humans. The overuse of antibiotics in aquaculture may lead to a high incidence of the...
can cause acute gastroenteritis, wound infections, and septicemia in humans. The overuse of antibiotics in aquaculture may lead to a high incidence of the multidrug-resistant (MDR) pathogen. Nevertheless, the genome evolution of in aquatic animals and the mechanism of its antibiotic tolerance remain to be further deciphered. Here, we investigated the molecular basis of the antibiotic tolerance of isolates ( = 3) originated from shellfish and crustaceans using comparative genomic and transcriptomic analyses. The genome sequences of the isolates were determined (5.0-5.3 Mb), and they contained 4709-5610 predicted protein-encoding genes, of which 823-1099 genes were of unknown functions. Comparative genomic analyses revealed a number of mobile genetic elements (MGEs, = 69), antibiotic resistance-related genes ( = 7-9), and heavy metal tolerance-related genes ( = 2-4). The isolates were resistant to sub-lethal concentrations (sub-LCs) of ampicillin (AMP, 512 μg/mL), kanamycin (KAN, 64 μg/mL), and streptomycin (STR, 16 μg/mL) ( < 0.05). Comparative transcriptomic analyses revealed that there were significantly altered metabolic pathways elicited by the sub-LCs of the antibiotics ( < 0.05), suggesting the existence of multiple strategies for antibiotic tolerance in . The results of this study enriched the genome database and should be useful for controlling the MDR pathogen worldwide.
PubMed: 38890902
DOI: 10.3390/foods13111674 -
Virulence Dec 2024The global surge in multidrug-resistant bacteria owing to antibiotic misuse and overuse poses considerable risks to human and animal health. With existing antibiotics...
The global surge in multidrug-resistant bacteria owing to antibiotic misuse and overuse poses considerable risks to human and animal health. With existing antibiotics losing their effectiveness and the protracted process of developing new antibiotics, urgent alternatives are imperative to curb disease spread. Notably, improving the bactericidal effect of antibiotics by using non-antibiotic substances has emerged as a viable strategy. Although reduced nicotinamide adenine dinucleotide (NADH) may play a crucial role in regulating bacterial resistance, studies examining how the change of metabolic profile and bacterial resistance following by exogenous administration are scarce. Therefore, this study aimed to elucidate the metabolic changes that occur in (), which exhibits resistance to various antibiotics, following the exogenous addition of NADH using metabolomics. The effects of these alterations on the bactericidal activity of neomycin were investigated. NADH enhanced the effectiveness of aminoglycoside antibiotics against ATCC15947, achieving bacterial eradication at low doses. Metabolomic analysis revealed that NADH reprogrammed the ATCC15947 metabolic profile by promoting purine metabolism and energy metabolism, yielding increased adenosine triphosphate (ATP) levels. Increased ATP levels played a crucial role in enhancing the bactericidal effects of neomycin. Moreover, exogenous NADH promoted the bactericidal efficacy of tetracyclines and chloramphenicols. NADH in combination with neomycin was effective against other clinically resistant bacteria, including , methicillin-resistant , and . These results may facilitate the development of effective approaches for preventing and managing -induced infections and multidrug resistance in aquaculture and clinical settings.
Topics: Edwardsiella tarda; Anti-Bacterial Agents; NAD; Aminoglycosides; Animals; Fish Diseases; Microbial Sensitivity Tests; Enterobacteriaceae Infections; Adenosine Triphosphate; Neomycin; Drug Synergism; Metabolomics; Drug Resistance, Multiple, Bacterial
PubMed: 38884466
DOI: 10.1080/21505594.2024.2367647 -
Microbiology Resource Announcements Jun 2024A Pacific native lineage of ST36 serotype O4:K12 was introduced into the Atlantic, which increased local source illnesses. To identify genetic determinants of virulence...
A Pacific native lineage of ST36 serotype O4:K12 was introduced into the Atlantic, which increased local source illnesses. To identify genetic determinants of virulence and ecological resiliency and track their transfer into endemic populations, we constructed a complete genome of a 2013 Atlantic-traced clinical isolate by hybrid assembly.
PubMed: 38864604
DOI: 10.1128/mra.00352-24 -
Microbiology Spectrum Jun 2024The incidence of infections, with high mortality rates in humans and aquatic animals, has escalated, highlighting a significant public health challenge. Currently,...
The incidence of infections, with high mortality rates in humans and aquatic animals, has escalated, highlighting a significant public health challenge. Currently, reliable markers to identify strains with high virulence potential are lacking, and the understanding of evolutionary drivers behind the emergence of pathogenic strains is limited. In this study, we analyzed the distribution of virulent genotypes and phenotypes to discern the infectious potential of strains isolated from three distinct sources. Most isolates, traditionally classified as biotype 1, possessed the virulence-correlated gene-C type. Environmental isolates predominantly exhibited YJ-like alleles, while clinical and diseased fish isolates were significantly associated with the gene and pathogenicity region XII. Hemolytic activity was primarily observed in the culture supernatants of clinical and diseased fish isolates. Genetic relationships, as determined by multiple-locus variable-number tandem repeat analysis, suggested that strains originating from the same source tended to cluster together. However, multilocus sequence typing revealed considerable genetic diversity across clusters and sources. A phylogenetic analysis using single nucleotide polymorphisms of diseased fish strains alongside publicly available genomes demonstrated a high degree of evolutionary relatedness within and across different isolation sources. Notably, our findings reveal no direct correlation between phylogenetic patterns, isolation sources, and virulence capabilities. This underscores the necessity for proactive risk management strategies to address pathogenic strains emerging from environmental reservoirs.IMPORTANCEAs the global incidence of infections rises, impacting human health and marine aquacultures, understanding the pathogenicity of environmental strains remains critical yet underexplored. This study addresses this gap by evaluating the virulence potential and genetic relatedness of strains, focusing on environmental origins. We conduct an extensive genotypic analysis and phenotypic assessment, including virulence testing in a wax moth model. Our findings aim to uncover genetic and evolutionary factors that drive pathogenic strain emergence in the environment. This research advances our ability to identify reliable virulence markers and understand the distribution of pathogenic strains, offering significant insights for public health and environmental risk management.
PubMed: 38860819
DOI: 10.1128/spectrum.00079-24 -
Frontiers in Public Health 2024In Ethiopia, despite major improvements seen in health service delivery system, the country continues to be significantly affected by cholera outbreaks. Cholera remains...
INTRODUCTION
In Ethiopia, despite major improvements seen in health service delivery system, the country continues to be significantly affected by cholera outbreaks. Cholera remains a significant public health problem among the vulnerable populations living in many resource-limited settings with poor access to safe and clean water and hygiene practices. Recurring cholera outbreaks are an indication of deprived water and sanitation conditions as well as weak health systems, contributing to the transmission and spread of the cholera infection.
OBJECTIVE
To assess the cholera outbreak, its challenges, and the way forward on public health interventions to solve the knowledge and health service delivery gaps related to cholera control in Guraghe Zone, Ethiopia, 2023.
METHODS
Active surveillance of the cholera outbreak was conducted in all kebeles and town administrative of Guraghe zone from 7/8/2023 to 30/10/2023. A total of 224 cholera cases were detected during the active surveillance method. Data obtained from Guraghe zone offices were exported to SPSS version 25 for additional analysis. The case fatality rate, incidence of the cases, and other descriptive variables were presented and described using figures and tables.
RESULT
A total of 224 cholera cases were detected through an active surveillance system. In this study, the case fatality rate of cholera outbreak was 2.6%. To tackle the cholera outbreak, the Guraghe zone health office collaborated with other stakeholders to prepare four cholera treatment centers. The absence of OCV, inaccessible safe water, low latrine coverage, inappropriate utilization of latrines, and absence of cholera laboratory rapid diagnostics test in Guraghe Zone are barriers to tackling the outbreak.
CONCLUSION
Ethiopia National Cholera Plan targeted eradicating cholera by 2030, 222 cholera outbreak occurred in Guraghe Zone, Ethiopia. To minimize and control cholera mortality rate oral cholera vaccinations should be employed in all areas of the region. Sustainable WASH measures should be guaranteed for the use of safe water and good hygiene practices. Early diagnosis and treatment should be initiated appropriately for those who are infected.
Topics: Cholera; Ethiopia; Humans; Disease Outbreaks; Adolescent; Female; Male; Sanitation; Public Health; Adult; Child; Middle Aged; Young Adult; Child, Preschool; Incidence
PubMed: 38859897
DOI: 10.3389/fpubh.2024.1355613