OmpK36

We investigated, by using all-atom molecular dynamics simulations, the effect of the asymmetric outer membrane layer of Gram-negative bacteria, composed in the outer leaflet by polar/charged lipopolysaccharides (LPS), on the electrostatic properties of general porins from the Enterobacteriaceae family. These porins constitute the main path for the facilitated diffusion of polar antibiotics to cross the outer membrane. As model system we selected OmpK36 from Klebsiella pneumoniae, the ortholog of OmpC from Escherichia coli...

Klebsiella pneumoniae is a major human pathogen, because it causes both community- and hospital-acquired infections. Several multidrug-resistant high-risk clones of K. pneumoniae have been reported worldwide, and these are responsible for high numbers of difficult-to-treat infections. In Greece, a K. pneumoniae ST39 high-risk clone was detected in 2019 in a survey of carbapenem- and/or colistin-resistant Enterobacteriacae. The present study included nine carbapenem-resistant K. pneumoniae (CRKP) isolates collected during a retrospective analysis from October 2020 to December 2020...

We evaluated the in vitro activity of meropenem-vaborbactam plus aztreonam (MEV-ATM) against 140 metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae isolates. Among them, 25 isolates (17.9%) displayed minimum inhibitory concentrations (MIC) ≥ 8 µg/mL, while 112 (80.0%) had MIC ≤ 2 µg/mL. Genomic analysis and subsequent gene cloning experiments revealed OmpK36 134-135GD-insertion and increased carbapenemase gene ( bla NDM-1 and bla OXA-48-like ) copy numbers are the main factors responsible for MEV-ATM non-susceptibility...

OBJECTIVES: K. pneumoniae is a common cause of severe hospital-acquired infections. In the present study we have characterized the whole-genome of two K. pneumoniae ST437 belonging to the clonal complex CC258. METHODS: The whole-genome sequencing was performed by MiSeq Illumina, with a 2×300bp paired-end run. ResFinder 4.4.2 was used to detect acquired antimicrobial resistance genes (ARGs) and chromosomal mutations. Mobile genetic elements (plasmids and ISs) were identified by MobileElementFinder v1...

INTRODUCTION: The spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a substantial severe global public health burden. Non-carbapenemase-producing CRKP (non-CP-CRKP) is increasingly recognized as the source of severe infections. METHODOLOGY: We analyzed the genotypic, and phenotypic profiles of non-CP-CRKP strains with the whole-genome sequences isolated between 2017 and 2019 and the clinical characterization of non-CP-CRKP infection. RESULTS: A total of 91 CRKP strains were collected, of which 5 (5...

Klebsiella pneumoniae ( K. pneumoniae ) exhibits the ability to form biofilms as a means of adapting to its adverse surroundings. K. pneumoniae in this biofilm state demonstrates remarkable resistance, evades immune system attacks, and poses challenges for complete eradication, thereby complicating clinical anti-infection efforts. Moreover, the precise mechanisms governing biofilm formation and disruption remain elusive. Recent studies have discovered that fingolimod (FLD) exhibits biofilm properties against Gram-positive bacteria...

PURPOSE: To characterize the resistance mechanisms affecting the cefepime-taniborbactam combination in a collection of carbapenemase-producing Enterobacterales (CPE) and carbapenem-resistant Pseudomonas spp. (predominantly P. aeruginosa; CRPA) clinical isolates. METHODS: CPE (n = 247) and CRPA (n = 170) isolates were prospectively collected from patients admitted to 8 Spanish hospitals. Susceptibility to cefepime-taniborbactam and comparators was determined by broth microdilution...

PURPOSE: OXA-48 producing Klebsiella pneumoniae is an emerging threat and outbreaks due to specific sequence types have been commonly reported. Here, we report an outbreak due to multidrug-resistant ST395 K. pneumoniae ST395. To the best of our knowledge, this is the first outbreak of K. pneumoniae ST395 harbouring blaOXA-48 genes in our country. METHODS: The strains were characterized by antimicrobial susceptibility, extended-spectrum β-lactamase (ESBL) and carbapenemase production, plasmid-mediated colistin, high-level aminoglycoside, and quinolone resistance...

OBJECTIVES: This study investigated a ceftazidime/avibactam (CZA)-resistant K. pneumoniae (NE368), isolated from a patient exposed to CZA, expressing a novel KPC-3 variant, named KPC-109. METHODS: Antimicrobial susceptibility testing was performed by reference broth microdilution. WGS analysis of NE368 was performed combining a short- and long-reads approach by Illumina and Nanopore technologies. Functional characterization of KPC-109 was performed investigating the impact of KPC-109 production on the β-lactam resistance phenotype of various Escherichia coli and Klebsiella pneumoniae strains, including derivatives of K...

OBJECTIVES: Ceftazidime/avibactam and meropenem/vaborbactam are preferred agents for Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC- Kp ) infections and are often used in combination with other agents. We aimed to characterize the synergy of combinations against KPC- Kp with varying ompK36 genotypes. METHODS: KPC- Kp that harboured ompK36 WT, IS 5 or glycine-aspartic acid duplication (GD) genotypes were selected. MICs were determined in triplicate...

BACKGROUND: Whole-genome sequencing (WGS) provides important information for the characterization, surveillance, and monitoring of antimicrobial resistance (AMR) determinants, particularly in cases of multi- and extensively drug-resistant microorganisms. We reported the results of a WGS analysis carried out on carbapenemases-producing Klebsiella pneumoniae , which causes hospital-acquired infections (HAIs) and is characterized by a marked resistance profile. METHODS: Clinical, phenotypic, and genotypic data were collected for the AMR surveillance screening program of the University Hospital of Sassari (Italy) during 2020-2021...

BACKGROUND: The aim of this study was to characterize the blaKPC-33 in a ST15-K19 ceftazidime-avibactam (CAZ-AVI) resistant Klebsiella pneumoniae strain after the antibiotic CAZ-AVI was approved for use in Wuxi No. 2 People's Hospital, China. MATERIALS AND METHODS: Antimicrobial susceptibility testing was performed by the microdilution broth method. Whole genome sequencing (WGS) was performed using PacBio II and MiSeq sequencers. High-quality reads were assembled using the SOAPdenovo and GapCloser v1...

In order to inform and anticipate potential strategies aimed at combating KPC-producing Klebsiella pneumoniae infections, we analyzed imipenem/relebactam and ceftazidime/avibactam single-step mutant frequencies, resistance development trajectories, differentially selected resistance mechanisms and their associated fitness cost using 4 representative high-risk K. pneumoniae clones. Mutant frequencies and mutant preventive concentrations were determined using agar plates containing incremental concentrations of β-lactam/β-lactamase inhibitor...

INTRODUCTION: Carbapenems are usually used in the treatment of infections caused by cephalosporin-resistant Enterobacterales ; however, the increase in carbapenem-resistant Enterobacterales (CRE) has become one of the most important problems in public health. Hafnia alvei is associated with intestinal and extraintestinal infections, especially in patients with any chronic disease or some type of immunosupression. H. alvei is resistant to first-generation aminopenicillins and cephalosporins owing to the β-lactamase (Amp C) in their chromosome; the only carbapenem-resistant Hafnia strain described until now was due to a lack of the OmpK36 protein that plays an important role in permeability to carbapenems...

Antibiotic resistance is driven by selection, but the degree to which a bacterial strain's evolutionary history shapes the mechanism and strength of resistance remains an open question. Here, we reconstruct the genetic and evolutionary mechanisms of carbapenem resistance in a clinical isolate of Klebsiella quasipneumoniae . A combination of short- and long-read sequencing, machine learning, and genetic and enzymatic analyses established that this carbapenem-resistant strain carries no carbapenemase-encoding genes...

The isolation of multidrug-resistant Klebsiella pneumoniae in hospitals is a major public health threat, increasing patient hospitalization costs, morbidity and mortality. Therefore, this work investigated the resistance mechanisms that produced different carbapenems susceptibility profiles in two isogenic strains of K. pneumoniae isolated from the same patient in a public hospital in Recife, Pernambuco. The genes that encode the main porins in K. pneumoniae, ompK35 and ompK36, and several beta-lactamase genes were analyzed...

To investigate ceftazidime/avibactam (CZA) resistance characteristics and mechanisms of bacteremic Enterobacteriales strains not previously treated with CZA, 9,708 strains were collected from 43 hospitals in 18 provinces across China from January 2019 to June 2020. Of them, MIC values of CZA in 165 (1.70%) strains were ≥8/4 mg/L. Ten (6.06%) CZA-resistant strains without metallo-β-lactamase production were obtained from the individuals without prior exposure to CZA, including six Escherichia coli (E...

To kill bacteria, bacteriophages (phages) must first bind to a receptor, triggering the release of the phage DNA into the bacterial cell. Many bacteria secrete polysaccharides that had been thought to shield bacterial cells from phage attack. We use a comprehensive genetic screen to distinguish that the capsule is not a shield but is instead a primary receptor enabling phage predation. Screening of a transposon library to select phage-resistant Klebsiella shows that the first receptor-binding event docks to saccharide epitopes in the capsule...

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated globally and is difficult to treat, causing increased morbidity and mortality rates in critically ill patients. We conducted a multicenter cross-sectional study of intensive care unit (ICU) inpatients in 78 hospitals to investigate the prevalence and molecular characteristics of CRKP in Henan Province, China, a hyperepidemic region. A total of 327 isolates were collected and downsampled to 189 for whole-genome sequencing. Molecular typing revealed that sequence type 11 (ST11) of clonal group 258 (CG258) was predominant (88...

PURPOSE: The study was conducted in Jilin province to investigate the mechanism involved in the antibiotic resistance and pathogenicity of Klebsiella pneumoniae (K. pneumoniae). METHODS: Lung samples were collected from the large-scale pig farms in Jilin Province. The antimicrobial susceptibility and mouse lethality assay were carried out. K. pneumoniae isolate JP20 with high virulence and antibiotic resistance was chosen for whole-genome sequencing. The complete sequence of its genome was annotated, and the virulence and antibiotic resistance mechanism were analyzed...