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PLoS Neglected Tropical Diseases Jun 2024Plague, a zoonotic disease caused by Yersinia pestis, was responsible for 3 historical human pandemics that killed millions of people. It remains endemic in rodent... (Review)
Review
BACKGROUND
Plague, a zoonotic disease caused by Yersinia pestis, was responsible for 3 historical human pandemics that killed millions of people. It remains endemic in rodent populations in Africa, Asia, North America, and South America but human plague is rare in most of these locations. However, human plague is still highly prevalent in Madagascar, which typically records a significant part of all annual global cases. This has afforded an opportunity to study contemporary human plague in detail using various typing methods for Y. pestis.
AIM
This review aims to summarize the methods that have been used to type Y. pestis in Madagascar along with the major discoveries that have been made using these approaches.
METHODS
Pubmed and Google Scholar were used to search for the keywords: "typing Yersinia pestis Madagascar," "evolution Yersinia pestis Madagascar," and "diversity Yersinia pestis Madagascar." Eleven publications were relevant to our topic and further information was retrieved from references cited in those publications.
RESULTS
The history of Y. pestis typing in Madagascar can be divided in 2 periods: the pre-genomics and genomics eras. During the pre-genomics era, ribotyping, direct observation of plasmid content and plasmid restriction fragment length polymorphisms (RFLP) were employed but only revealed a limited amount of diversity among Malagasy Y. pestis strains. Extensive diversity only started to be revealed in the genomics era with the use of clustered regularly interspaced palindromic repeats (CRISPR), multiple-locus variable number tandem repeats (VNTR) analysis (MLVA), and single-nucleotide polymorphisms (SNPs) discovered from whole genome sequences. These higher-resolution genotyping methods have made it possible to highlight the distribution and persistence of genotypes in the different plague foci of Madagascar (Mahajanga and the Central and Northern Highlands) by genotyping strains from the same locations across years, to detect transfers between foci, to date the emergence of genotypes, and even to document the transmission of antimicrobial resistant (AMR) strains during a pneumonic plague outbreak. Despite these discoveries, there still remain topics that deserve to be explored, such as the contribution of horizontal gene transfer to the evolution of Malagasy Y. pestis strains and the evolutionary history of Y. pestis in Madagascar.
CONCLUSIONS
Genotyping of Y. pestis has yielded important insights on plague in Madagascar, particularly since the advent of whole-genome sequencing (WGS). These include a better understanding of plague persistence in the environment, antimicrobial AMR and multi-drug resistance in Y. pestis, and the person-to-person spread of pneumonic plague. Considering that human plague is still a significant public health threat in Madagascar, these insights can be useful for controlling and preventing human plague in Madagascar and elsewhere, and also are relevant for understanding the historical pandemics and the possible use of Y. pestis as a biological weapon.
Topics: Yersinia pestis; Madagascar; Plague; Humans; Animals; Genotype; Genotyping Techniques
PubMed: 38935608
DOI: 10.1371/journal.pntd.0012252 -
Microbial Ecology Jun 2024Antimicrobial resistance (AMR) is a major public health threat, exacerbated by the ability of bacteria to rapidly disseminate antimicrobial resistance genes (ARG). Since...
Antimicrobial resistance (AMR) is a major public health threat, exacerbated by the ability of bacteria to rapidly disseminate antimicrobial resistance genes (ARG). Since conjugative plasmids of the incompatibility group P (IncP) are ubiquitous mobile genetic elements that often carry ARG and are broad-host-range, they are important targets to prevent the dissemination of AMR. Plasmid-dependent phages infect plasmid-carrying bacteria by recognizing components of the conjugative secretion system as receptors. We sought to isolate plasmid-dependent phages from wastewater using an avirulent strain of Salmonella enterica carrying the conjugative IncP plasmid pKJK5. Irrespective of the site, we only obtained bacteriophages belonging to the genus Alphatectivirus. Eleven isolates were sequenced, their genomes analyzed, and their host range established using S. enterica, Escherichia coli, and Pseudomonas putida carrying diverse conjugative plasmids. We confirmed that Alphatectivirus are abundant in domestic and hospital wastewater using culture-dependent and culture-independent approaches. However, these results are not consistent with their low or undetectable occurrence in metagenomes. Therefore, overall, our results emphasize the importance of performing phage isolation to uncover diversity, especially considering the potential of plasmid-dependent phages to reduce the spread of ARG carried by conjugative plasmids, and to help combat the AMR crisis.
Topics: Plasmids; Wastewater; Bacteriophages; Genome, Viral; Escherichia coli; Host Specificity; Pseudomonas putida; Salmonella enterica; Phylogeny
PubMed: 38935220
DOI: 10.1007/s00248-024-02401-3 -
Archives of Microbiology Jun 2024Marine hydrocarbonoclastic bacteria can use polycyclic aromatic hydrocarbons as carbon and energy sources, that makes these bacteria highly attractive for bioremediation...
Marine hydrocarbonoclastic bacteria can use polycyclic aromatic hydrocarbons as carbon and energy sources, that makes these bacteria highly attractive for bioremediation in oil-polluted waters. However, genomic and metabolic differences between species are still the subject of study to understand the evolution and strategies to degrade PAHs. This study presents Rhodococcus ruber MSA14, an isolated bacterium from marine sediments in Baja California, Mexico, which exhibits adaptability to saline environments, a high level of intrinsic pyrene tolerance (> 5 g L), and efficient degradation of pyrene (0.2 g L) by 30% in 27 days. Additionally, this strain demonstrates versatility by using naphthalene and phenanthrene as individual carbon sources. The genome sequencing of R. ruber MSA14 revealed a genome spanning 5.45 Mbp, a plasmid of 72 kbp, and three putative megaplasmids, lengths between 110 and 470 Kbp. The bioinformatics analysis of the R. ruber MSA14 genome revealed 56 genes that encode enzymes involved in the peripheral and central pathways of aromatic hydrocarbon catabolism, alkane, alkene, and polymer degradation. Within its genome, R. ruber MSA14 possesses genes responsible for salt tolerance and siderophore production. In addition, the genomic analysis of R. ruber MSA14 against 13 reference genomes revealed that all compared strains have at least one gene involved in the alkanes and catechol degradation pathway. Overall, physiological assays and genomic analysis suggest that R. ruber MSA14 is a new haloalkalitolerant and hydrocarbonoclastic strain toward a wide range of hydrocarbons, making it a promising candidate for in-depth characterization studies and bioremediation processes as part of a synthetic microbial consortium, as well as having a better understanding of the catabolic potential and functional diversity among the Rhodococci group.
Topics: Rhodococcus; Biodegradation, Environmental; Genome, Bacterial; Polycyclic Aromatic Hydrocarbons; Geologic Sediments; Genomics; Naphthalenes; Phylogeny; Phenanthrenes; Salt Tolerance; Pyrenes
PubMed: 38935150
DOI: 10.1007/s00203-024-04050-z -
Journal of the American Heart... Jun 2024The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This...
Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C-Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury.
BACKGROUND
The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine.
METHODS AND RESULTS
Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming.
CONCLUSIONS
This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.
PubMed: 38934866
DOI: 10.1161/JAHA.124.034805 -
Microbiology Resource Announcements Jun 2024We report the complete genome sequence of strain EL101, isolated from the tree bark of in Kampar, Perak, Malaysia, obtained using Q20+ Nanopore Sequencing chemistry....
We report the complete genome sequence of strain EL101, isolated from the tree bark of in Kampar, Perak, Malaysia, obtained using Q20+ Nanopore Sequencing chemistry. The assembled genome has a total length of 5,324,685 bp, comprising a circular chromosome, a linear chromid, and two non-Ti circular plasmids.
PubMed: 38934609
DOI: 10.1128/mra.00298-24 -
Microbiology Spectrum Jun 2024, an organism recently classified within the Pseudomonadaceae family, has been detected in diverse sources such as human tissues, animal guts, industrial fermenters, and...
, an organism recently classified within the Pseudomonadaceae family, has been detected in diverse sources such as human tissues, animal guts, industrial fermenters, and decomposition environments, suggesting a diverse ecological role. However, a large knowledge gap exists in how functions. In this comparative genomic analysis, adaptations indicative of habitat specificity among strains and genomic similarity to known opportunistic pathogens are revealed. Genomic investigation reveals a core metabolic utilization of multiple oxidative and non-oxidative catabolic pathways, suggesting adaptability to varied environments and carbon sources. The genomic repertoire of includes secondary metabolites, such as antimicrobials and siderophores, indicative of its involvement in microbial competition and resource acquisition. Additionally, the presence of transposases, prophages, plasmids, and Clustered Regularly Interspaced Short Palindromic Repeats-Cas systems in genomes suggests mechanisms for horizontal gene transfer and defense against viral predation. This comprehensive genomic analysis expands our understanding on the ecological functions, community interactions, and potential virulence of , while emphasizing its adaptability and diverse capabilities across environmental and host-associated ecosystems.IMPORTANCEAs the microbial world continues to be explored, new organisms will emerge with beneficial and/or pathogenetic impact. is a species originally isolated from clinical human tissue and fluid samples but has not been attributed to disease. Since its classification, has been found in animal guts, animal waste, decomposing remains, and biogas fermentation reactors. This is the first study to provide an in-depth view of the metabolic potential of publicly available genomes belonging to this species through a comparative genomics and draft pangenome calculation approach. It was found that is metabolically versatile and likely adapts to diverse energy sources and environments, which may make it useful for bioremediation and in industrial settings. A range of virulence factors and antibiotic resistances were also detected, suggesting may operate as an undescribed opportunistic pathogen.
PubMed: 38934605
DOI: 10.1128/spectrum.04157-23 -
Microbiology Resource Announcements Jun 2024The genome sequence of multidrug-resistant RT01-5M1 strain isolated from Canadian farmed salmon was determined using Oxford nanopore and Illumina MiSeq sequencers. The...
The genome sequence of multidrug-resistant RT01-5M1 strain isolated from Canadian farmed salmon was determined using Oxford nanopore and Illumina MiSeq sequencers. The assembled chromosome was estimated at 5,699,993 bp in size, with two plasmids, 164,879 bp and 82,046 bp. The chromosome and smaller plasmid contained antimicrobial resistance genes.
PubMed: 38934593
DOI: 10.1128/mra.00153-24 -
Current Cancer Drug Targets Jun 2024Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) is involved in the progression of hepatocellular carcinoma (HCC).
INTRODUCTION
Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) is involved in the progression of hepatocellular carcinoma (HCC).
AIMS
This study aimed to investigate the inhibitory effect of gamma-tocotrienol (γ-T3) on the proliferation and growth of HSD17B4-overexpressing HepG2 cells.
METHODS
HepG2 cells were transfected with empty or HSD17B4-overexpressing plasmids, followed by vitamin E (VE) or γ-T3 treatment. MTS assay, Western blotting, qRT-PCR, and flow cytometry were employed to assess cell proliferation, protein expression, mRNA levels, and apoptosis. HSD17B4 interaction with γ-T3 was assessed by quantifying γ-T3 in the collected precipitate of HSD17B4 using anti-flag magnetic beads. Tumor xenografts were established in NSG mice, and tumor growth was monitored.
RESULTS
HSD17B4 overexpression significantly promoted HepG2 cell proliferation, which was effectively counteracted by VE or γ-T3 treatment in a dose-dependent manner. VE and γ-T3 did not exert their effects through direct regulation of HSD17B4 expression. Instead, γ-T3 was found to interact with HSD17B4, inhibiting its activity in catalyzing the conversion of estradiol (E2) into estrone. Moreover, γ-T3 treatment led to a reduction in cyclin D1 expression and suppressed key proliferation signaling pathways, such as ERK, MEK, AKT, and STAT3. Additionally, γ-T3 promoted apoptosis in HSD17B4-overexpressing HepG2 cells. In an in vivo model, γ-T3 effectively reduced the growth of HepG2 xenograft tumors.
CONCLUSION
In conclusion, our study demonstrates that γ-T3 exhibits potent anti-proliferative and anti-tumor effects against HepG2 cells overexpressing HSD17B4. These findings highlight the therapeutic potential of γ-T3 in HCC treatment and suggest its role in targeting HSD17B4-associated pathways to inhibit tumor growth and enhance apoptosis.
PubMed: 38934283
DOI: 10.2174/0115680096319171240623091614 -
Gynecologic and Obstetric Investigation Jun 2024Endometriosis (EMs) commonly occurs in reproductive women. We explored the mechanism of methyltransferase-like 14 (METTL14) on human endometriotic stromal cell (ESC;...
OBJECTIVE
Endometriosis (EMs) commonly occurs in reproductive women. We explored the mechanism of methyltransferase-like 14 (METTL14) on human endometriotic stromal cell (ESC; HEM15A) proliferation, migration and invasion, to provide novel therapy for EMs.
METHODS
HEM15A and human endometrial stromal cells (HESCs) were cultured in vitro. HEM15A cells were treated with oe-METTL14 and oe-zinc finger E-box-binding protein 1 (ZEB1) plasmids, N6-methyladenosine (m6A) inhibitor 3-deazaadenosine (3-DAA) and the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway inhibitor isoprenaline (ISO). After identifying HEM15A and HESCs, METTL14, ZEB1, p-ERK1/2/ERK1/2 and p-MEK/MEK levels, and cell proliferation, migration and invasion were assessed. The modification sites of ZEB1 and m6A were predicted using SRAMP database, with m6A modification level assessed by MeRIP. The binding of YT521-B homology domain 2 (YTHDF2) to ZEB1 messenger RNA (mRNA), and ZEB1 stability and mRNA level were tested.
RESULTS
Compared with HESCs, METTL14 level in HEM15A was significantly reduced. METTL14 overexpression in HEM15A prominently increased its proliferation, migration and invasion. METTL14 overexpression notably elecated m6A-methylated ZEB1 mRNA level and reduced the stability and expression of ZEB1 mRNA. Further m6A modification inhibition increased ZEB1 mRNA stability and mRNA and protein levels, and decreased ZEB1 m6A modification level. ZEB1 upregulation partially reversed METTL14 overexpression-inhibited HEM15A proliferation, migration and invasion. METTL14 inhibited the MEK/ERK signaling activation by regulating ZEB1, and the MEK/ERK signaling activation partly averted METTL14-suppressed proliferation, migration and invasion.
CONCLUSION
METTL14 lowered ZEB1 expression by regulating ZEB1 m6A modification levels, thereby inhibiting the MEK/ERK pathway activation and ESC proliferation, migration and invasion.
PubMed: 38934184
DOI: 10.1159/000539656 -
Infection and Drug Resistance 2024Carbapenem-resistant (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective -lactam/-lactamase inhibitors against...
BACKGROUND
Carbapenem-resistant (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective -lactam/-lactamase inhibitors against CRKP. However, reports of resistance to CZA, mainly caused by carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed to describe the resistance characteristics of KPC-12, a novel KPC variant identified from a CZA resistant .
METHODS
The YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability.
RESULTS
Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 confers high-level resistance to CZA (16/4 μg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants.
DISCUSSION
Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible.
PubMed: 38933778
DOI: 10.2147/IDR.S465699