TerC Proteins Function During Protein Secretion to Metalate Exoenzymes DOI Creative Commons
John D. Helmann, Bixi He, Ankita J. Sachla

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: May 17, 2023

Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported are appropriately metalated is less clear. We provide evidence that TerC family proteins function in metalation of enzymes during export through the general secretion (Sec-dependent) pathway. Bacillus subtilis strains lacking MeeF(YceF) and MeeY(YkoY) have a reduced capacity for protein greatly level manganese (Mn) secreted proteome. MeeF MeeY copurify with secretory pathway, their absence FtsH membrane protease essential viability. also required efficient Mn2+-dependent lipoteichoic acid synthase (LtaS), membrane-localized enzyme an extracytoplasmic active site. Thus, MeeY, representative widely conserved transporters, co-translocational extracellular enzymes.

Language: Английский

Animal models of Klebsiella pneumoniae mucosal infections DOI Creative Commons
Lucas Assoni,

Ana Julia Melo Couto,

Brenda Vieira

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: March 15, 2024

Klebsiella pneumoniae is among the most relevant pathogens worldwide, causing high morbidity and mortality, which worsened by increasing rates of antibiotic resistance. It a constituent host microbiota different mucosa, that can invade cause infections in many sites. The development new treatments prophylaxis against this pathogen rely on animal models to identify potential targets evaluate efficacy possible side effects therapeutic agents or vaccines. However, validity data generated highly dependable choosing adequately reproduce hallmarks human diseases. present review summarizes current knowledge used investigate K. infections, with focus mucosal advantages limitations each model are discussed compared; applications, extrapolations subjects future modifications improve techniques also presented. While mice widely species studies, they such as natural resistance difficulties reproducing main steps infections. Other models, Drosophila melanogaster (fruit fly), Caenorhabditis elegans, Galleria mellonella Danio rerio (zebrafish), contribute understanding specific aspects infection process, bacterial lethality colonization innate immune system response, however, but do not immunological complexity mammals. In conclusion, choice will depend mainly questions being addressed study, while better interplay between virulence factors responses provide deeper comprehension disease process aid effective preventive/therapeutic strategies.

Language: Английский

Citations

11
TerC proteins function during protein secretion to metalate exoenzymes DOI Creative Commons
Bixi He, Ankita J. Sachla, John D. Helmann

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 4, 2023

Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported are appropriately metalated is less clear. We provide evidence that TerC family proteins function in metalation of enzymes during export through the general secretion (Sec-dependent) pathway. Bacillus subtilis strains lacking MeeF(YceF) and MeeY(YkoY) have a reduced capacity for protein greatly level manganese (Mn) secreted proteome. MeeF MeeY copurify with secretory pathway, their absence FtsH membrane protease essential viability. also required efficient Mn

Language: Английский

Citations

17
Fitness factor genes conserved within the multi-species core genome of Gram-negative Enterobacterales species contribute to bacteremia pathogenesis DOI Creative Commons
Harry L. T. Mobley, Mark T. Anderson, Bridget S. Moricz

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012495 - e1012495

Published: Aug. 23, 2024

There is a critical gap in knowledge about how Gram-negative bacterial pathogens, using survival strategies developed for other niches, cause lethal bacteremia. Facultative anaerobic species of the Enterobacterales order are most common bacteremia, including Escherichia coli , Klebsiella pneumoniae Serratia marcescens Citrobacter freundii and Enterobacter hormaechei . Bacteremia often leads to sepsis, life-threatening organ dysfunction resulting from unregulated immune responses infection. Despite lack specialization this host environment, pathogens nearly half bacteremia cases annually. Based on our existing Tn-Seq fitness factor data murine model combined with comparative genomics five above, we prioritized 18 conserved genes or operons further characterization. Mutants were constructed all species. Each mutant was used cochallenge C57BL/6 mice via tail vein injection along each respective wild-type strain determine competitive indices gene. Five genes, when mutated, attenuated mutants four spleen liver ( tatC ruvA gmhB wzxE arcA ). additional validated as outcompeted by three, four, xerC prc apaGH atpG aroC Overall, 17 at least one liver. Together, these findings allow development pathogenesis that may include future targets therapy against bloodstream infections.

Language: Английский

Citations

5
The Klebsiella pneumoniae tellurium resistance gene terC contributes to both tellurite and zinc resistance DOI Creative Commons

Ruixiang Yang,

Shuang Han,

Yanshuang Yu

et al.

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

ABSTRACT Klebsiella pneumoniae is widely recognized as a pathogen responsible for hospital-acquired infections and community-acquired invasive infections. It has rapidly become significant global public health threat due to the emergence of hypervirulent multidrug-resistant strains, which have increased challenges associated with treating life-threatening Tellurium resistance genes are widespread on virulence plasmids in K. isolates. However, core function ter operon ( terZABCDEF ) remains unclear. In this study, P1927 strain was isolated from sputum hospitalized pneumonia patient. The operon, along antimicrobial genes, identified large hybrid plasmid P1927. We generated terC deletion mutant demonstrated that exhibited reduced Galleria mellonella larva infection model. Further physiological functional analysis revealed not only important Te(IV) but also Zn(II), Mn(II), phage infection. All were highly inducible by stronger inducer than Te(IV), terBCDE induced Mn(II). Collectively, our study demonstrates novel functions TerC Zn(II) . IMPORTANCE health. Although clinical isolates, its been proposed proteins encoded form multi-site metal-binding complex, exact still unknown. TerC, central component tellurium determinant, previously shown interact outer membrane OmpA KpsD Escherichia coli , suggesting potential changes structure properties. Here, we report confers infection, be strong operon. Furthermore, factor. Taken together, results expand understanding role providing deeper insights into link between heavy metal(loid) determinants pathogenic bacteria.

Language: Английский

Citations

0
Whole Genome Sequencing Reveals High Genetic Diversity, Diverse Repertoire of Virulence-Associated Genes and Limited Antibiotic Resistance Genes among Commensal Escherichia coli from Food Animals in Uganda DOI Creative Commons
Denis K. Byarugaba, Godfrey Wokorach,

Stephen Alafi

et al.

Microorganisms, Journal Year: 2023, Volume and Issue: 11(8), P. 1868 - 1868

Published: July 25, 2023

Commensal Escherichia coli with broad repertoire of virulence and antimicrobial resistance (AMR) genes pose serious public health risks as reservoirs AMR virulence. This study undertook whole genome characterization commensal E. from food-producing animals in Uganda to investigate their variability (resistome virulome). We established that the had high genomic diversity 38 sequence types, 24 FimH 33 O-antigen serotypes randomly distributed within three phylogroups (A, B1, E). A greater proportion (≥93.65%) were resistant amoxicillin/clavulanate ampicillin antibiotics. The isolates AmpC beta-lactamase producers dominated by blaEC-15 (71.88%) tet(A) (20.31%) besides a diverse armory virulence-associated class exotoxin, adhesins, iron uptake, serine protease autotransporters which varied host species. Cattle found be major source carrying Shiga toxin genes, whereas swine was main colicin-like Usp gene. underscores importance livestock carrier large traits potential causing disease humans acquiring more genetic traits.

Language: Английский

Citations

7
Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking DOI Creative Commons
Daiana A. Capdevila, Johnma J. Rondón, Katherine A. Edmonds

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Transition metals function as structural and catalytic cofactors for a large diversity of proteins enzymes that collectively comprise the metalloproteome. Metallostasis considers all cellular processes, notably metal sensing, metalloproteome remodeling, trafficking (or allocation) ensure functional integrity adaptability Bacteria employ both protein RNA-based mechanisms sense intracellular transition bioavailability orchestrate systems-level outputs maintain metallostasis. In this review, we contextualize metallostasis by briefly discussing specialized roles play in biology. We then offer comprehensive perspective on metalloregulatory metal-sensing riboswitches, defining general principles within each sensor superfamily capture how specificity is encoded sequence, selectivity can be leveraged downstream synthetic biology biotechnology applications. This followed discussion recent work highlights selected outputs, including remodeling allocation metallochaperones to client compartments. close places where more needed fill gaps our understanding

Language: Английский

Citations

2
Fitness Factor Genes Conserved within the Multi-species Core Genome of Gram-negative Enterobacterales Species Contribute to Bacteremia Pathogenesis DOI Open Access
Harry L. T. Mobley, Mark T. Anderson, Bridget S. Moricz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 18, 2024

Abstract There is a critical gap in knowledge about how Gram-negative bacterial pathogens, using survival strategies developed for other niches, cause lethal bacteremia. Facultative anaerobic species of the Enterobacterales order are most common bacteremia, including Escherichia coli , Klebsiella pneumoniae Serratia marcescens, Citrobacter freundii, and Enterobacter hormaechei . Bacteremia often leads to sepsis, life-threatening organ dysfunction resulting from an unregulated immune response infection. Despite lack specialization this host environment, pathogens nearly half bacteremia cases annually. Based on our existing Tn-Seq fitness factor data murine model combined with comparative genomics five above, we prioritized 18 conserved genes or operons further characterization. Each mutant each was used cochallenge C57BL/6 mice via tail vein injection along respective wild-type strain determine competitive indices gene operon. Among species, found three genes, that when mutated, attenuated all spleen liver ( tatC, ruvA, gmhB ). Nine additional were validated as outcompeted by four xerC wzxE arcA prc apaGH atpG lpdA ubiH aroC Overall, 17 mutants at least one liver. Together, these findings allow development pathogenesis may include future targets therapy against bloodstream infections. >Author Summary Frequent plague ICUs, bone marrow transplant units, inpatient facilities. Nearly infections caused bacteria. The E. K. pneumoniae, S. C. freundii leading causes An alarming proportion due antibiotic-resistant isolates, which times more likely kill than antibiotic-susceptible isolates. Clearly, need new therapeutic treat sepsis. Previously, it has been unclear what contribute their ability survive hostile environment. We have previously undertaken unbiased genetic screens identify shared genera required blood blood-filtering organs. These encode proteins maintain proton motive force, resist antimicrobial peptides complement, mediate genome maintenance, transport key metabolites proteins, avoid oxidative stress, acquire iron, regulate pathways. Mutants, constructed high infection mouse

Language: Английский

Citations

1
Biological properties and genetic structure of clinic isolates of Klebsiella pneumoniae species DOI Creative Commons
N. L. Belkova, E. S. Klimenko, У. М. Немченко

et al.

Acta Biomedica Scientifica (East Siberian Biomedical Journal), Journal Year: 2024, Volume and Issue: 9(1), P. 53 - 63

Published: March 25, 2024

Klebsiella pneumoniae (Kp) species complex is a genetically and ecologically diverse group of bacteria that causes wide range infections in humans animals. The aim. To carry out biological characterization genotyping based on the study different loci clinical isolates. Materials methods . object was three isolates from biotopes patients regional children’s multidisciplinary hospital. We used bacteriological, molecular genetic bioinformatic methods. Genotyping carried using Pasteur Institute service for strains K. complex. Results All were sensitive to antimicrobial drugs carbapenem (imipenem, meropenem) tetracycline groups (tigecycline), demonstrated high sensitivity polyvalent bacteriophage. antibiotic resistance Kp ODKB-16 ODKB-81 seven eight drugs, respectively, registered Based results multi-locus sequence typing, all assigned Kp1 phylogroup, K2 type differed type, scgMLST629 profile KL type. strain identified as ST-65, scgST-11107, KL2; ODKB-07 – ST-219, scgST-6401, KL125KL114; ST-86, scgST-2800, KL2KL30. virulence gene clusters AbST, CbST, YbST, SmST, RmST have been characterized only genome isolate, allowing it be highly virulent with multidrug (MDR). Additionally, genes responsible synthesis types 1 3 fimbrial adhesins strains, ter operon ODKB-16. Resistome analysis showed had 2b genotype. Plasmids found genomes (IncI2) (IncFIA + IncFIB IncHI1B). Conclusion. comprehensive framework genomic taxonomy isolates, which can contribute unification global peculiarities developing microevolution bacterial pathogens.

Language: Английский

Citations

1
Insights into the microbiota of raw milk from seven breeds animals distributing in Xinjiang China DOI Creative Commons

Baolong Luo,

Fan Dong, Yuyang Liu

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 23, 2024

Owing to its high nutritional content, raw milk contains a rich microbiota. Thus, study microorganisms present in available Xinjiang China, 142 samples from seven animal breeds (cow, sheep, goat, donkey, horse, camel, and yak) four regions (Hami, Tarbagatay, Kashgar, Ili) were analyzed by high-throughput DNA sequencing. These characterized 10 dominant phyla. Proteobacteria (68.33%) was the major phylum, followed Firmicutes (18.80%) Thermi (3.16%). Horse contained more Bacteroidetes, sheep Gammaproteobacteria, donkey unclassified sequences. Camel highest lowest bacterial diversity compared with that remaining samples, respectively. Additionally, spoilage microorganisms, including Chryseobacterium , Propionibacterium Flavobacterium pathogenic bacteria, Ochrobactrum anthropi Sphingomonas prevalent horse yak milk, whereas probiotic lactic acid bacteria (LAB), such as Leuconostoc Lactococcus or Lactobacillus camel milk. Furthermore, Moraxella abundantly Acinetobacter abundant Pseudomonas relatively Overall, specific harmful found obtained different animals, which provided basis for preventing controlling growth of well investigating resources

Language: Английский

Citations

1
Genomic Profile of a Multidrug-Resistant Klebsiella pneumoniae Strain Isolated from a Urine Specimen DOI
Jonathan Arauz-Cabrera,

Dolores A Marquez-Salazar,

Ricardo Delgadillo-Valles

et al.

Current Microbiology, Journal Year: 2024, Volume and Issue: 81(9)

Published: July 18, 2024

Language: Английский

Citations

0