K2 capsular polysaccharide degradation by a bacteriophage depolymerase does not require trimer formation.

Unlabelled: K2-capsular is a hypervirulent pathogen that causes fatal infections. Here, we describe a phage tailspike protein, named K2-2, that specifically depolymerizes the K2 capsular polysaccharide (CPS) of into tetrasaccharide repeating units. Nearly half of the products contained -acetylation, which was thought crucial to the immunogenicity of CPS.

Identification of three capsule depolymerases in a bacteriophage infecting Klebsiella pneumoniae capsular types K7, K20, and K27 and therapeutic application.

Background: Klebsiella pneumoniae capsular types K1, K2, K5, K20, K54, and K57 are prevalent hypervirulent types associated with community infections, and worrisomely, hypervirulent strains that acquired drug resistance have been found. In the search for alternative therapeutics, studies have been conducted on phages that infect K. pneumoniae K1, K2, K5, and K57-type strains and their phage-encoded depolymerases.

Decolonization of carbapenem-resistant from the intestinal microbiota of model mice by phages targeting two surface structures.

Background: is a normal component of the human gastrointestinal tract microbiota. However, in some cases, it can cause disease. Over the past 20 years, the prevalence of antibiotic-resistant bacteria, such as carbapenem-resistant (CRKP), has been increasing.

Development of Capsule Polysaccharide-Conjugated Vaccine Candidates Using Phage Depolymerases.

is an important pathogen associated with nosocomial infection and has developed increasing resistance to antibiotics such as extended-spectrum β-lactams and carbapenem. In recent years, isolates have emerged as a major cause of global community-acquired infections such as pneumonia and pyogenic liver abscess. Although serotypes K1 and K2 have been identified as the predominant capsular types associated with invasive infections, no vaccine is commercially available, probably due to immunogenicity loss in the traditional depolymerization method to obtain capsule polysaccharide (CPS) for the preparation of conjugated vaccine.

Transporter Genes and fosA Associated With Fosfomycin Resistance in Carbapenem-Resistant .

Infections caused by carbapenem-resistant (CRKP) are of significant clinical concern worldwide. Fosfomycin is one of the limited treatment options for CRKP. However, resistance to fosfomycin in CRKP has been observed.

Structural and biological insights into Klebsiella pneumoniae surface polysaccharide degradation by a bacteriophage K1 lyase: implications for clinical use.

Background: K1 capsular polysaccharide (CPS)-associated Klebsiella pneumoniae is the primary cause of pyogenic liver abscesses (PLA) in Asia. Patients with PLA often have serious complications, ultimately leading to a mortality of ~ 5%. This K1 CPS has been reported as a promising target for development of glycoconjugate vaccines against K.

A hexasaccharide from capsular polysaccharide of carbapenem-resistant Klebsiella pneumoniae KN2 is a ligand of Toll-like receptor 4.

Klebsiella pneumoniae serotype KN2 is a carbapenem-resistant strain and leads to the health care-associated infections, such as bloodstream infections. Its capsular polysaccharide (CPS) was isolated and cleaved by a specific enzyme from a bacteriophage into a hexasaccharide-repeating unit. With GC-MS, NMR, and Mass analyses, the structure of KN2 CPS was determined to be {→3)-β-D-Glcp-(1→3)-[α-D-GlcpA-(1→4)-β-D-Glcp-(1→6)]-α-D-Galp-(1→6)-β-D-Galp-(1→3)-β-D-Galp-(1→}.

Aberrant Upregulation of Indoleamine 2,3-Dioxygenase 1 Promotes Proliferation and Metastasis of Hepatocellular Carcinoma Cells via Coordinated Activation of AhR and β-Catenin Signaling.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Chronic liver inflammation due to hepatitis virus infection and other major effectors is a major risk factor of HCC. Indoleamine 2,3-dioxygenase 1 (IDO1), a heme enzyme highly expressed upon stimulation with proinflammatory cytokines such as interferon-γ (IFN-γ), is activated to modulate the tumor microenvironment and potentially crucial in the development of certain cancer types.

Invasive Pathobionts Contribute to Colon Cancer Initiation by Counterbalancing Epithelial Antimicrobial Responses.

Background & Aims: Microbiota dysbiosis and mucosa-associated bacteria are involved in colorectal cancer progression. We hypothesize that an interaction between virulent pathobionts and epithelial defense promotes tumorigenesis.

Methods: Chemical-induced CRC mouse model was treated with antibiotics at various phases.

Risk factors and mechanisms of in vivo emergence of colistin resistance in carbapenem-resistant Klebsiella pneumoniae.

Colistin is one of the last-resort antibiotics for treating carbapenem-resistant Klebsiella pneumoniae (CRKP). However, colistin resistance in CRKP poses a global antimicrobial crisis, as therapeutic options are limited. We investigated risk factors for in vivo emergence of colistin resistance in CRKP and explored the underlying resistance mechanisms.

Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery.

The capability of gut microbiota in degrading foods and drugs administered orally can result in diversified efficacies and toxicity interpersonally and cause significant impact on human health. Production of atherogenic trimethylamine N-oxide (TMAO) from carnitine is a gut microbiota-directed pathway and varies widely among individuals. Here, we demonstrated a personalized TMAO formation and carnitine bioavailability from carnitine supplements by differentiating individual TMAO productivities with a recently developed oral carnitine challenge test (OCCT).

A Glutamine Insertion at Codon 432 of RpoB Confers Rifampicin Resistance in .

Tuberculosis (TB) is an infectious respiratory disease caused by and one of the top 10 causes of death worldwide. Treating TB is challenging; successful treatment requires a long course of multiple antibiotics. Rifampicin (RIF) is a first-line drug for treating TB, and the development of RIF-resistant makes treatment even more difficult.

A Synthetic Carbohydrate-Protein Conjugate Vaccine Candidate against Serotype K2.

causes pneumonia and liver abscesses in humans worldwide and contains virulence factor capsular polysaccharides and lipopolysaccharides linked to the cell wall. Although capsular polysaccharides are good antigens for vaccine production and capsular oligosaccharides conjugate vaccines are proven effective against infections caused by encapsulated pathogens, there is still no vaccine available. One obstacle is that the capsular polysaccharide of a dominated serotype K2 is difficult to synthesize chemically due to the three 1,2- linkages in its structure.

Two Novel Mutations Conferring Isoniazid Resistance in .

Tuberculosis (TB), an infectious disease caused by , is among the top 10 leading causes of death worldwide. The treatment course for TB is challenging; it requires antibiotic administration for at least 6 months, and bacterial drug resistance makes treatment even more difficult. Understanding the mechanisms of resistance is important for improving treatment.

Prophage Excision in Serotype 19A ST320 Promote Colonization: Insight Into Its Evolution From the Ancestral Clone Taiwan 19F-14 (ST236).

19A ST320, a multidrug-resistant strain with high disease severity that notoriously spread before the use of expanded pneumococcal conjugate vaccines, was derived from a capsular switching event between an international strain Taiwan 19F-14 (ST236) and a serotype 19A strain. However, the molecular mechanisms underlying the adaptive evolution of 19F ST236 to 19A ST320 are unknown. In this study, we compared 19A ST320 to its ancestral clone, 19F ST236, in terms of adherence to respiratory epithelial cells, whole transcriptome, and ability to colonize a young mouse model.

Identification of three podoviruses infecting Klebsiella encoding capsule depolymerases that digest specific capsular types.

Klebsiella pneumoniae is an important human pathogen causing opportunistic nosocomial and community-acquired infections. A major public health concern regarding K. pneumoniae is the increasing incidence of multidrug-resistant strains.

A Novel Role for the Klebsiella pneumoniae Sap (Sensitivity to Antimicrobial Peptides) Transporter in Intestinal Cell Interactions, Innate Immune Responses, Liver Abscess, and Virulence.

Klebsiella pneumoniae is an important human pathogen causing hospital-acquired and community-acquired infections. Systemic K. pneumoniae infections may be preceded by gastrointestinal colonization, but the basis of this bacterium's interaction with the intestinal epithelium remains unclear.

Klebsiella pneumoniae Type VI Secretion System Contributes to Bacterial Competition, Cell Invasion, Type-1 Fimbriae Expression, and In Vivo Colonization.

Background: We previously isolated a Klebsiella pneumoniae strain, NTUH-K2044, from a community-acquired pyogenic liver abscess (PLA) patient. Analysis of the NTUH-K2044 genome revealed that this strain harbors 2 putative type VI secretion system (T6SS)-encoding gene clusters.

Methods: The distribution of T6SS genes in the PLA and intestinal-colonizing K pneumoniae clinical isolates was examined.

Role of the ESX-1 Secretion System in Sliding Motility and Biofilm Formation.

is a close relative of that can cause systemic tuberculosis-like infections in ectotherms and skin infections in humans. Sliding motility correlates with biofilm formation and virulence in most bacteria. In this study, we used a sliding motility assay to screen 2,304 transposon mutants of NTUH-M6885 and identified five transposon mutants with decreased sliding motility.

A putative RND-type efflux pump, H239_3064, contributes to colistin resistance through CrrB in Klebsiella pneumoniae.

Background: Colistin is one of the last-resort antibiotics used to treat carbapenem-resistant Klebsiella pneumoniae infection. Our previous studies indicated that clinical strains encoding CrrB with amino acid substitutions exhibited higher colistin resistance (MICs ≥512 mg/L) than did colistin-resistant strains encoding mutant MgrB, PmrB or PhoQ.

Objectives: CrrAB may regulate another unknown mechanism(s) contributing to colistin resistance, besides modifications of LPS with 4-amino-4-deoxy-l-arabinose and phosphoethanolamine.

Two T7-like Bacteriophages, K5-2 and K5-4, Each Encodes Two Capsule Depolymerases: Isolation and Functional Characterization.

Two Klebsiella bacteriophages K5-2 and K5-4, which are able to infect and grow on either capsular types K30/K69 and K5 or K8 and K5 of Klebsiella strains, were isolated and characterized. Each phage contained two open reading frames (ORFs), which encoded two putative capsule depolymerases, respectively. The first ORF encoded tail fiber proteins, which have K30/K69 depolymerase and K8 depolymerase activities.

High Serum Lipopolysaccharide-Binding Protein Level in Chronic Hepatitis C Viral Infection Is Reduced by Anti-Viral Treatments.

Background: Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon.

Klebsiella Phage ΦK64-1 Encodes Multiple Depolymerases for Multiple Host Capsular Types.

The genome of the multihost bacteriophage ΦK64-1, capable of infecting capsular types K1, K11, K21, K25, K30, K35, K64, and K69, as well as new capsular types KN4 and KN5, was analyzed and revealed that 11 genes (, , , , , , , , , , and ) encode proteins with amino acid sequence similarity to tail fibers/spikes or lyases. previously was shown to encode a K64 capsule depolymerase (K64dep). Specific capsule-degrading activities of an additional eight putative capsule depolymerases (S2-4 against K1, S1-1 against K11, S1-3 against K21, S2-2 against K25, S2-6 against K30/K69, S2-3 against K35, S1-2 against KN4, and S2-1 against KN5) was demonstrated by expression and purification of the recombinant proteins.

Identification of a capsular variant and characterization of capsular acetylation in Klebsiella pneumoniae PLA-associated type K57.

Klebsiella pneumoniae can cause community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) is important for its virulence. Among 79 capsular (K) types discovered thus far, K57 is often associated with PLA.