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Vaccine Jun 2024Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets,...
Distributions of candidate vaccine Targets, virulence Factors, and resistance features of invasive group B Streptococcus using Whole-Genome Sequencing: A Multicenter, population-based surveillance study.
BACKGROUND
Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants.
METHODS
We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China.
RESULTS
Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively."
CONCLUSIONS
The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.
Topics: Humans; Streptococcus agalactiae; Whole Genome Sequencing; Virulence Factors; Infant; Streptococcal Infections; Streptococcal Vaccines; Infant, Newborn; China; Female; Serogroup; Male; Drug Resistance, Bacterial; Genome, Bacterial; Anti-Bacterial Agents
PubMed: 38692955
DOI: 10.1016/j.vaccine.2024.04.062 -
Current Opinion in Microbiology Jun 2024Bacterial biofilms are a prevalent multicellular life form in which individual members can undergo significant functional differentiation and are typically embedded in a... (Review)
Review
Bacterial biofilms are a prevalent multicellular life form in which individual members can undergo significant functional differentiation and are typically embedded in a complex extracellular matrix of proteinaceous fimbriae, extracellular DNA, and exopolysaccharides (EPS). Bacteria have evolved at least four major mechanisms for EPS biosynthesis, of which the synthase-dependent systems for bacterial cellulose secretion (Bcs) represent not only key biofilm determinants in a wide array of environmental and host-associated microbes, but also an important model system for the studies of processive glycan polymerization, cyclic diguanylate (c-di-GMP)-dependent synthase regulation, and biotechnological polymer applications. The secreted cellulosic chains can be decorated with additional chemical groups or can pack with various degrees of crystallinity depending on dedicated enzymatic complexes and/or cytoskeletal scaffolds. Here, I review recent progress in our understanding of synthase-dependent EPS biogenesis with a focus on common and idiosyncratic molecular mechanisms across diverse cellulose secretion systems.
Topics: Cellulose; Polysaccharides, Bacterial; Bacteria; Biofilms; Bacterial Proteins; Cyclic GMP; Glucosyltransferases
PubMed: 38688160
DOI: 10.1016/j.mib.2024.102476 -
Chemosphere Jun 2024Silver (Ag) is a pivotal transition metal with applications in multiple industries, necessitating efficient recovery techniques. Despite various proposed methods for...
Silver (Ag) is a pivotal transition metal with applications in multiple industries, necessitating efficient recovery techniques. Despite various proposed methods for silver recovery from wastewaters, challenges persist especially for low concentrations. In this context, bioreduction by bacteria like Geobacter sulfurreducens, offers a promising approach by converting Ag(I) to Ag nanoparticles. To reveal the mechanisms driving microbial Ag(I) reduction, we conducted transcriptional profiling of G. sulfurreducens under Ag(I)-reducing condition. Integrated transcriptomic and protein-protein interaction network analyses identified significant transcriptional shifts, predominantly linked to c-type cytochromes, NADH, and pili. When compared to a pilus-deficient strain, the wild-type strain exhibited distinct cytochrome gene expressions, implying specialized functional roles. Additionally, despite a down-regulation in NADH dehydrogenase genes, we observed up-regulation of specific downstream cytochrome genes, highlighting NADH's potential role as an electron donor in the Ag(I) reduction process. Intriguingly, our findings also highlight the significant influence of pili on the morphology of the resulting Ag nanoparticles. The presence of pili led to the formation of smaller and more crystallized Ag nanoparticles. Overall, our findings underscore the intricate interplay of cytochromes, NADH, and pili in Ag(I) reduction. Such insights suggest potential strategies for further enhancing microbial Ag(I) reduction.
Topics: Geobacter; Silver; Fimbriae, Bacterial; Transcriptome; Cytochromes; NAD; Oxidation-Reduction; Metal Nanoparticles
PubMed: 38685325
DOI: 10.1016/j.chemosphere.2024.142174 -
The Journal of Biological Chemistry Jun 2024The biphasic assembly of Gram-positive pili begins with the covalent polymerization of distinct pilins catalyzed by a pilus-specific sortase, followed by the cell wall...
The biphasic assembly of Gram-positive pili begins with the covalent polymerization of distinct pilins catalyzed by a pilus-specific sortase, followed by the cell wall anchoring of the resulting polymers mediated by the housekeeping sortase. In Actinomyces oris, the pilus-specific sortase SrtC2 not only polymerizes FimA pilins to assemble type 2 fimbriae with CafA at the tip, but it can also act as the anchoring sortase, linking both FimA polymers and SrtC1-catalyzed FimP polymers (type 1 fimbriae) to peptidoglycan when the housekeeping sortase SrtA is inactive. To date, the structure-function determinants governing the unique substrate specificity and dual enzymatic activity of SrtC2 have not been illuminated. Here, we present the crystal structure of SrtC2 solved to 2.10-Å resolution. SrtC2 harbors a canonical sortase fold and a lid typical for class C sortases and additional features specific to SrtC2. Structural, biochemical, and mutational analyses of SrtC2 reveal that the extended lid of SrtC2 modulates its dual activity. Specifically, we demonstrate that the polymerizing activity of SrtC2 is still maintained by alanine-substitution, partial deletion, and replacement of the SrtC2 lid with the SrtC1 lid. Strikingly, pilus incorporation of CafA is significantly reduced by these mutations, leading to compromised polymicrobial interactions mediated by CafA. In a srtA mutant, the partial deletion of the SrtC2 lid reduces surface anchoring of FimP polymers, and the lid-swapping mutation enhances this process, while both mutations diminish surface anchoring of FimA pili. Evidently, the extended lid of SrtC2 enables the enzyme the cell wall-anchoring activity in a substrate-selective fashion.
Topics: Cysteine Endopeptidases; Bacterial Proteins; Aminoacyltransferases; Fimbriae, Bacterial; Fimbriae Proteins; Crystallography, X-Ray; Actinomyces; Substrate Specificity; Models, Molecular
PubMed: 38679328
DOI: 10.1016/j.jbc.2024.107329 -
Infection, Genetics and Evolution :... Jul 2024Whopping cough (or Pertussis) is an acute infectious respiratory disease caused by Bordetella pertussis bacteria. The disease is highly transmissible and can be fatal in...
Whopping cough (or Pertussis) is an acute infectious respiratory disease caused by Bordetella pertussis bacteria. The disease is highly transmissible and can be fatal in children under two years old. Since the introduction of vaccine immunization in 1940, Pertussis incidence decreased worldwide. In Brazil, the immunization was introduced in 1977 using the whole cell (wP) vaccine. Despite the high vaccination coverage, an unexpected increase in the number of observed Pertussis cases was observed in 2012. In this year, 2257 cases were reported exceeding the average incidence rate of <1000 cases per year until 2010. This outbreak reached a peak level in 2014 and ended in 2018 according to the Brazilian National Surveillance System (SINAN). To understand the relationship between the outbreak and the vaccination, bacterial isolates (n = 136) from the Brazilian Midwest region obtained during the outbreak were submitted to genotyping of two vaccine loci: ptxP and fim3. Most of isolates (102) were obtained from nursing children (29 days to 2 years old). Genotyping of 94 isolates revealed that fim3-24/ptxP-3 was the most prevalent genotype (68%) associated with the outbreak peak. Two additional genotypes were also observed: fim3-1/ptxP-3 (15%) and fim3-3/ptxP-3 (17%). Conversely, the fim3-1/ptxP-2 genotype, which is harbored by the strain used in the wP vaccine (Bp137), was not observed. These results showed that B. pertussis circulating strains in the outbreak analyzed were different from the strain used for Pertussis immunization in Brazil. These observations provide insights that could be used to target vaccination programs to prevent future whooping cough outbreaks in Brazil.
Topics: Brazil; Humans; Disease Outbreaks; Whooping Cough; Bordetella pertussis; Pertussis Vaccine; Genotype; Infant; Child, Preschool; Female; Male; Infant, Newborn; Child; Antigens, Bacterial; Virulence Factors, Bordetella; Fimbriae Proteins
PubMed: 38679113
DOI: 10.1016/j.meegid.2024.105599 -
Viruses Apr 2024The phage PRR1 belongs to the family, a group of ssRNA bacteriophages that infect Gram-negative bacteria. The variety of host cells is determined by the specificity of...
The phage PRR1 belongs to the family, a group of ssRNA bacteriophages that infect Gram-negative bacteria. The variety of host cells is determined by the specificity of PRR1 to a pilus encoded by a broad host range of IncP-type plasmids that confer multiple types of antibiotic resistance to the host. Using strain PAO1 as a host, we analyzed the PRR1 infection cycle, focusing on cell lysis. PRR1 infection renders cells sensitive to lysozyme approximately 20 min before the start of a drop in suspension turbidity. At the same time, infected cells start to accumulate lipophilic anions. The on-line monitoring of the entire infection cycle showed that single-gene-mediated lysis strongly depends on the host cells' physiological state. The blockage of respiration or a reduction in the intracellular ATP concentration during the infection resulted in the inhibition of lysis. The same effect was observed when the synthesis of PRR1 lysis protein was induced in an expression system. In addition, lysis was strongly dependent on the level of aeration. Dissolved oxygen concentrations sufficient to support cell growth did not ensure efficient lysis, and a coupling between cell lysis initiation and aeration level was observed. However, the duration of the drop in suspension turbidity did not depend on the level of aeration.
Topics: Bacteriolysis; Escherichia coli; Host Specificity; Muramidase; Pseudomonas aeruginosa; Pseudomonas Phages
PubMed: 38675985
DOI: 10.3390/v16040645 -
Genes Apr 2024The giant grouper fish (), one of the largest and rarest groupers, is a fast-growing economic fish. Grouper sperm is often used for cross-breeding with other fish and...
The giant grouper fish (), one of the largest and rarest groupers, is a fast-growing economic fish. Grouper sperm is often used for cross-breeding with other fish and therefore sperm cryopreservation is important. However, freezing damage cannot be avoided. Herein, we performed a transcriptome analysis to compare fresh and frozen sperm of the giant grouper with frozen storage times of 0, 23, 49, and 61 months. In total, 1911 differentially expressed genes (DEGs), including 91 in El-0-vs-El-23 (40 upregulated and 51 downregulated), 251 in El-0-vs-El-49 (152 upregulated and 69 downregulated), and 1569 in El-0-vs-El-61 (984 upregulated and 585 downregulated), were obtained in the giant grouper sperm. DEGs were significantly increased at 61 months of cryopreservation ( < 0.05). GO and KEGG enrichment analyses of the DEGs revealed significant enrichment in the pilus assembly, metabolic process, MAPK signaling pathway, apoptosis, and P53 signaling pathway. Time-series expression profiling of the DEGs showed that consistently upregulated modules were also significantly enriched in signaling pathways associated with apoptosis. Four genes, , , , and , were associated with mitochondria and flagella in a weighted correlation network analysis. These genes may play an important role in the response to sperm freezing. The experimental results show that long-term cryopreservation results in freezing damage to the giant grouper sperm. This study provides rich data for studies of the mechanism underlying frozen fish sperm damage as well as a technical reference and evaluation index for the long-term cryopreservation of fish sperm.
Topics: Animals; Male; Cryopreservation; Transcriptome; Spermatozoa; Gene Expression Profiling; Bass; Semen Preservation; Fish Proteins
PubMed: 38674457
DOI: 10.3390/genes15040523 -
In Silico Pharmacology 2024Chronic periodontitis caused by the bacteria is thought to be a risk factor for the advancement of oral squamous cell carcinoma (OSCC). Virulence factors of include...
Identification of bio-active secondary metabolites from Actinobacteria as potential drug targets against in oral squamous cell carcinoma using molecular docking and dynamics study.
UNLABELLED
Chronic periodontitis caused by the bacteria is thought to be a risk factor for the advancement of oral squamous cell carcinoma (OSCC). Virulence factors of include gingipains, outer membrane surface lipoproteins, and fimbriae contribute to the activation of oncogenic pathways in OSCC by up-regulating different cytokines. Gingipains (Arg and Lys) proteases have an important role in the activation of proMMP-9, which promotes cellular invasion and metastatic ability of OSCC. Thus gingipains and MMP-9 were actively investigated as potential therapeutic targets in OSCC therapy. Various natural bioactive compounds from Actinobacteria have been explored for their anticancer potential in a variety of cancers, but very few studies have been reported in OSCC. Therefore, the current study is focused to identify potential actinobacterial compounds that can be considered as a therapeutic target against gingipains and inflammatory proteins in OSCC through high-throughput virtual screening, Molecular Docking (MD), and Molecular Dynamics Simulation (MDS) approaches. A total of 179 bioactive secondary metabolites of Actinobacteria were explored for their binding affinity against six virulence proteins of . The Molecular Docking studies revealed that among 179 metabolites screened, Actinosporin G showed a highly acceptable binding affinity of -7.9 kcal/mol with RgpB (1CVR), and exhibited multi-protein targeting and drug-likeness property and passed level of toxicity. Comprehensive docking interaction of the best top-ranked Actinosporin G with OSCC-related protein targets illustrated high binding affinity towards MMP-9 and JAK-1 proteins among all targeted receptor proteins. The molecular dynamic (MD) simulation has been executed for the metabolite Actinosporin G for both bacterial gingipain (RgpB) and MMP-9 & JAK-1 showed stable intermolecular binding with both hydrogen and hydrophobic interactions. In conclusion, this work suggests that the bioactive secondary metabolite of Actinosporin G from Actinobacteria genera may serve as a promising therapy for -induced OSCC.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40203-024-00209-0.
PubMed: 38666247
DOI: 10.1007/s40203-024-00209-0 -
The ISME Journal Jan 2024Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary...
Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Prolonged infection allows the accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonizing upper airway environments. Here, we model this process using an experimental evolution approach. Pseudomonas aeruginosa PAO1, which is not airway adapted, was serially passaged, separately, in media chemically reflective of upper or lower airway environments. To explore whether the CF environment selects for unique traits, we separately passaged PAO1 in airway-mimicking media with or without CF-specific factors. Our findings demonstrated that all airway environments-sinus and lungs, under CF and non-CF conditions-selected for loss of twitching motility, increased resistance to multiple antibiotic classes, and a hyper-biofilm phenotype. These traits conferred increased airway colonization potential in an in vivo model. CF-like conditions exerted stronger selective pressures, leading to emergence of more pronounced phenotypes. Loss of twitching was associated with mutations in type IV pili genes. Type IV pili mediate surface attachment, twitching, and induction of cAMP signalling. We additionally identified multiple evolutionary routes to increased biofilm formation involving regulation of cyclic-di-GMP signalling. These included the loss of function mutations in bifA and dipA phosphodiesterase genes and activating mutations in the siaA phosphatase. These data highlight that airway environments select for traits associated with sessile lifestyles and suggest upper airway niches support emergence of phenotypes that promote establishment of lung infection.
Topics: Pseudomonas aeruginosa; Pseudomonas Infections; Adaptation, Physiological; Biofilms; Animals; Lung; Fimbriae, Bacterial; Second Messenger Systems; Cystic Fibrosis; Mice; Humans; Anti-Bacterial Agents; Cyclic GMP; Mutation; Phenotype
PubMed: 38647527
DOI: 10.1093/ismejo/wrae065 -
Scientific Reports Apr 2024tRNA modifications play a crucial role in ensuring accurate codon recognition and optimizing translation levels. While the significance of these modifications in...
tRNA modifications play a crucial role in ensuring accurate codon recognition and optimizing translation levels. While the significance of these modifications in eukaryotic cells for maintaining cellular homeostasis and physiological functions is well-established, their physiological roles in bacterial cells, particularly in pathogenesis, remain relatively unexplored. The TusDCB protein complex, conserved in γ-proteobacteria like Escherichia coli, is involved in sulfur modification of specific tRNAs. This study focused on the role of TusDCB in the virulence of uropathogenic E. coli (UPEC), a bacterium causing urinary tract infections. The findings indicate that TusDCB is essential for optimal production of UPEC's virulence factors, including type 1 fimbriae and flagellum, impacting the bacterium's ability to aggregate in bladder epithelial cells. Deletion of tusDCB resulted in decreased virulence against urinary tract infection mice. Moreover, mutant TusDCB lacking sulfur transfer activity and tusE- and mnmA mutants revealed the indispensability of TusDCB's sulfur transfer activity for UPEC pathogenicity. The study extends its relevance to highly pathogenic, multidrug-resistant strains, where tusDCB deletion reduced virulence-associated bacterial aggregation. These insights not only deepen our understanding of the interplay between tRNA sulfur modification and bacterial pathogenesis but also highlight TusDCB as a potential therapeutic target against UPEC strains resistant to conventional antimicrobial agents.
Topics: Animals; Mice; Virulence; Escherichia coli Proteins; Uropathogenic Escherichia coli; Escherichia coli Infections; Urinary Tract Infections; Virulence Factors; Transferases
PubMed: 38637685
DOI: 10.1038/s41598-024-59614-2