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SLAS Technology Dec 2023Cholera is a waterborne disease caused by Vibrio cholerae bacteria generally transmitted through contaminated food or water sources. Although it has been eradicated in... (Review)
Review
Cholera is a waterborne disease caused by Vibrio cholerae bacteria generally transmitted through contaminated food or water sources. Although it has been eradicated in most Western countries, cholera continues to be a highly transmitted and lethal disease in several African and Southeast Asian countries. Unfortunately, current diagnostic methods for cholera have challenges including high cost or delayed diagnoses that can lead to increased disease transmission during pandemics, while current treatments such as therapeutic drugs and vaccines have limited efficacy against drug-resistant serogroups of Vibrio cholerae. As such, new solutions that can treat cholera in an efficient manner that avoids Vibrio cholerae's adaptive immunity are needed. Nanoparticles (NPs) are a suitable platform for enhancing current theranostic tools because of their biocompatibility and ability to improve drug circulation and targeting. Nanoparticle surfaces can also be modified with various protein receptors targeting cholera toxins produced by Vibrio cholerae. This review will address recent developments in diagnostics, therapeutics, and prevention against cholera particularly focusing on the use of metal-based nanoparticles and organic nanoparticles. We will then discuss future directions regarding nanoparticle research for cholera.
Topics: Humans; Cholera; Vibrio cholerae; Metal Nanoparticles
PubMed: 37925157
DOI: 10.1016/j.slast.2023.10.006 -
Nature Microbiology Aug 2023To explore favourable niches while avoiding threats, many bacteria use a chemotaxis navigation system. Despite decades of studies on chemotaxis, most signals and sensory...
To explore favourable niches while avoiding threats, many bacteria use a chemotaxis navigation system. Despite decades of studies on chemotaxis, most signals and sensory proteins are still unknown. Many bacterial species release D-amino acids to the environment; however, their function remains largely unrecognized. Here we reveal that D-arginine and D-lysine are chemotactic repellent signals for the cholera pathogen Vibrio cholerae. These D-amino acids are sensed by a single chemoreceptor MCP co-transcribed with the racemase enzyme that synthesizes them under the control of the stress-response sigma factor RpoS. Structural characterization of this chemoreceptor bound to either D-arginine or D-lysine allowed us to pinpoint the residues defining its specificity. Interestingly, the specificity for these D-amino acids appears to be restricted to those MCP orthologues transcriptionally linked to the racemase. Our results suggest that D-amino acids can shape the biodiversity and structure of complex microbial communities under adverse conditions.
Topics: Vibrio cholerae; Amino Acids; Lysine; Bacterial Proteins; Bacteria; Arginine
PubMed: 37365341
DOI: 10.1038/s41564-023-01419-6 -
The intersection between host-pathogen interactions and metabolism during Vibrio cholerae infection.Current Opinion in Microbiology Feb 2024Vibrio cholerae (V. cholerae), the etiological agent of cholera, uses cholera toxin (CT) to cause severe diarrheal disease. Cholera is still a significant cause of... (Review)
Review
Vibrio cholerae (V. cholerae), the etiological agent of cholera, uses cholera toxin (CT) to cause severe diarrheal disease. Cholera is still a significant cause of mortality worldwide with about half of all cholera cases and deaths occurring in children under five. Owing to the lack of cost-effective vaccination and poor vaccine efficacy in children, there is a need for alternative preventative and therapeutic strategies. Recent advances in our knowledge of the interplay between CT-induced disease and host-pathogen metabolism have opened the door for investigating how modulation of intestinal metabolism by V. cholerae during disease impacts host intestinal immunity, the gut microbiota, and pathogen-phage interactions. In this review article, we examine recent progress in our understanding of host-pathogen interactions during V. cholerae infection and discuss future work deciphering how modulation of gut metabolism during cholera intersects these processes to enable successful fecal-oral transmission of the pathogen.
Topics: Child; Humans; Cholera; Vibrio cholerae; Cholera Toxin; Host-Pathogen Interactions; Bacteriophages
PubMed: 38215547
DOI: 10.1016/j.mib.2023.102421 -
ELife Sep 2023The seventh pandemic of the diarrheal cholera disease, which began in 1960, is caused by the Gram-negative bacterium . Its environmental persistence provoking recurring...
The seventh pandemic of the diarrheal cholera disease, which began in 1960, is caused by the Gram-negative bacterium . Its environmental persistence provoking recurring sudden outbreaks is enabled by rapid adaption to changing environments involving sensory proteins like ToxR and ToxS. Located at the inner membrane, ToxR and ToxS react to environmental stimuli like bile acid, thereby inducing survival strategies for example bile resistance and virulence regulation. The presented crystal structure of the sensory domains of ToxR and ToxS in combination with multiple bile acid interaction studies, reveals that a bile binding pocket of ToxS is only properly folded upon binding to ToxR. Our data proposes an interdependent functionality between ToxR transcriptional activity and ToxS sensory function. These findings support the previously suggested link between ToxRS and VtrAC-like co-component systems. Besides VtrAC, ToxRS is now the only experimentally determined structure within this recently defined superfamily, further emphasizing its significance. In-depth analysis of the ToxRS complex reveals its remarkable conservation across various species, underlining the significance of conserved residues in the ToxS barrel and the more diverse ToxR sensory domain. Unravelling the intricate mechanisms governing ToxRS's environmental sensing capabilities, provides a promising tool for disruption of this vital interaction, ultimately inhibiting survival and virulence. Our findings hold far-reaching implications for all strains that rely on the ToxRS system as a shared sensory cornerstone for adapting to their surroundings.
Topics: Transcription Factors; DNA-Binding Proteins; Bacterial Proteins; Bile; Vibrio; Vibrio cholerae; Bile Acids and Salts; Gene Expression Regulation, Bacterial
PubMed: 37768326
DOI: 10.7554/eLife.88721 -
Nature Microbiology Oct 2023Since 2016, Yemen has been experiencing the largest cholera outbreak in modern history. Multidrug resistance (MDR) emerged among Vibrio cholerae isolates from cholera...
Since 2016, Yemen has been experiencing the largest cholera outbreak in modern history. Multidrug resistance (MDR) emerged among Vibrio cholerae isolates from cholera patients in 2018. Here, to characterize circulating genotypes, we analysed 260 isolates sampled in Yemen between 2018 and 2019. Eighty-four percent of V. cholerae isolates were serogroup O1 belonging to the seventh pandemic El Tor (7PET) lineage, sub-lineage T13, whereas 16% were non-toxigenic, from divergent non-7PET lineages. Treatment of severe cholera with macrolides between 2016 and 2019 coincided with the emergence and dominance of T13 subclones carrying an incompatibility type C (IncC) plasmid harbouring an MDR pseudo-compound transposon. MDR plasmid detection also in endemic non-7PET V. cholerae lineages suggested genetic exchange with 7PET epidemic strains. Stable co-occurrence of the IncC plasmid with the SXT family of integrative and conjugative element in the 7PET background has major implications for cholera control, highlighting the importance of genomic epidemiological surveillance to limit MDR spread.
Topics: Humans; Cholera; Vibrio cholerae O1; Yemen; Plasmids; Genomics
PubMed: 37770747
DOI: 10.1038/s41564-023-01472-1 -
Wiener Klinische Wochenschrift Nov 2023Vibrio cholerae, an important human pathogen, is naturally occurring in specific aquatic ecosystems. With very few exceptions, only the cholera-toxigenic strains... (Review)
Review
Vibrio cholerae, an important human pathogen, is naturally occurring in specific aquatic ecosystems. With very few exceptions, only the cholera-toxigenic strains belonging to the serogroups O1 and O139 are responsible for severe cholera outbreaks with epidemic or pandemic potential. All other nontoxigenic, non-O1/non-O139 V. cholerae (NTVC) strains may cause various other diseases, such as mild to severe infections of the ears, of the gastrointestinal and urinary tracts as well as wound and bloodstream infections. Older, immunocompromised people and patients with specific preconditions have an elevated risk. In recent years, worldwide reports demonstrated that NTVC infections are on the rise, caused amongst others by elevated water temperatures due to global warming.The aim of this review is to summarize the knowledge gained during the past two decades on V. cholerae infections and its occurrence in bathing waters in Austria, with a special focus on the lake Neusiedler See. We investigated whether NTVC infections have increased and which specific environmental conditions favor the occurrence of NTVC. We present an overview of state of the art methods that are currently available for clinical and environmental diagnostics. A preliminary public health risk assessment concerning NTVC infections related to the Neusiedler See was established. In order to raise awareness of healthcare professionals for NTVC infections, typical symptoms, possible treatment options and the antibiotic resistance status of Austrian NTVC isolates are discussed.
Topics: Humans; Vibrio cholerae; Cholera; Austria; Ecosystem
PubMed: 37530997
DOI: 10.1007/s00508-023-02241-0 -
The Journal of Biological Chemistry Dec 2023Aggregation behavior provides bacteria protection from harsh environments and threats to survival. Two uncharacterized proteases, LapX and Lap, are important for Vibrio...
Aggregation behavior provides bacteria protection from harsh environments and threats to survival. Two uncharacterized proteases, LapX and Lap, are important for Vibrio cholerae liquid-based aggregation. Here, we determined that LapX is a serine protease with a preference for cleavage after glutamate and glutamine residues in the P1 position, which processes a physiologically based peptide substrate with a catalytic efficiency of 180 ± 80 Ms. The activity with a LapX substrate identified by a multiplex substrate profiling by mass spectrometry screen was 590 ± 20 Ms. Lap shares high sequence identity with an aminopeptidase (termed VpAP) from Vibrio proteolyticus and contains an inhibitory bacterial prepeptidase C-terminal domain that, when eliminated, increases catalytic efficiency on leucine p-nitroanilide nearly four-fold from 5.4 ± 4.1 × 10 Ms to 20.3 ± 4.3 × 10 Ms. We demonstrate that LapX processes Lap to its mature form and thus amplifies Lap activity. The increase is approximately eighteen-fold for full-length Lap (95.7 ± 5.6 × 10 Ms) and six-fold for Lap lacking the prepeptidase C-terminal domain (11.3 ± 1.9 × 10 Ms). In addition, substrate profiling reveals preferences for these two proteases that could inform in vivo function. Furthermore, purified LapX and Lap restore the timing of the V. cholerae aggregation program to a mutant lacking the lapX and lap genes. Both proteases must be present to restore WT timing, and thus they appear to act sequentially: LapX acts on Lap, and Lap acts on the substrate involved in aggregation.
Topics: Bacterial Proteins; Leucyl Aminopeptidase; Peptides; Serine Proteases; Substrate Specificity; Vibrio cholerae; Catalysis
PubMed: 37898401
DOI: 10.1016/j.jbc.2023.105386 -
Gut Microbes 2024Although metals are essential for life, they are toxic to bacteria in excessive amounts. Therefore, the maintenance of metal homeostasis is critical for bacterial...
Although metals are essential for life, they are toxic to bacteria in excessive amounts. Therefore, the maintenance of metal homeostasis is critical for bacterial physiology and pathogenesis. is a significant food-borne pathogen that mainly causes acute gastroenteritis in humans and acute hepatopancreatic necrosis disease in shrimp. Herein, we report that ZntA functions as a zinc (Zn) and cadmium (Cd) homeostasis mechanism and contributes to oxidative stress resistance and virulence in . is remarkably induced by Zn, copper, cobalt, nickel (Ni), and Cd, while ZntA promotes growth under excess Zn/Ni and Cd conditions via maintaining Zn and Cd homeostasis, respectively. The growth of Δ was inhibited under iron (Fe)-restricted conditions, and the inhibition was associated with Zn homeostasis disturbance. Ferrous iron supplementation improved the growth of Δ under excess Zn, Ni or Cd conditions. The resistance of Δ to HO-induced oxidative stress also decreased, and its virulence was attenuated in zebrafish models. Quantitative real-time PCR, mutagenesis, and β-galactosidase activity assays revealed that ZntR positively regulates expression by binding to its promoter. Collectively, the ZntR-regulated ZntA is crucial for Zn and Cd homeostasis and contributes to oxidative stress resistance and virulence in .
Topics: Humans; Animals; Zinc; Cadmium; Vibrio parahaemolyticus; Virulence; Hydrogen Peroxide; Zebrafish; Gastrointestinal Microbiome; Homeostasis; Oxidative Stress; Iron
PubMed: 38466137
DOI: 10.1080/19490976.2024.2327377 -
Frontiers in Cellular and Infection... 2023Gram-negative species are major foodborne pathogens often associated with seafood intake that causes gastroenteritis. On food surfaces, biofilm formation by species...
Gram-negative species are major foodborne pathogens often associated with seafood intake that causes gastroenteritis. On food surfaces, biofilm formation by species enhances the resistance of bacteria to disinfectants and antimicrobial agents. Hence, an efficient antibacterial and antibiofilm approach is urgently required. This study examined the antibacterial and antivirulence effects of chromones and their 26 derivatives against and . 6-Bromo-3-formylchromone (6B3FC) and 6-chloro-3-formylchromone (6C3FC) were active antibacterial and antibiofilm compounds. Both 6B3FC and 6C3FC exhibited minimum inhibitory concentrations (MICs) of 20 µg/mL for planktonic cell growth and dose-dependently inhibited biofilm formation. Additionally, they decreased swimming motility, protease activity, fimbrial agglutination, hydrophobicity, and indole production at 20 µg/mL which impaired the growth of the bacteria. Furthermore, the active compounds could completely inhibit the slimy substances and microbial cells on the surface of the squid and shrimp. The most active compound 6B3FC inhibited the gene expression associated in quorum sensing and biofilm formation (, ), pathogenicity (), and membrane integrity () in . However, toxicity profiling using seed germination and models suggests that 6C3FC may have moderate effect at 50 µg/mL while 6B3FC was toxic to the nematodes 20-100 µg/mL. These findings suggest chromone analogs, particularly two halogenated formylchromones (6B3FC and 6C3FC), were effective antimicrobial and antibiofilm agents against in the food and pharmaceutical sectors.
Topics: Animals; Vibrio parahaemolyticus; Anti-Infective Agents; Anti-Bacterial Agents; Caenorhabditis elegans; Biofilms
PubMed: 37662002
DOI: 10.3389/fcimb.2023.1234668