Genomic Characteristics of Extended Spectrum ß-Lactamase Producing Escherichia coli Isolates Recovered from a District Hospital in China.

Purpose: The isolation rate of extended spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing, posing a challenge to clinical anti-infective therapy. This study aims to provide new insight into the genomic characteristics and antimicrobial resistance mechanisms of extended spectrum ß-lactamase producing E. coli isolates recovered from a district hospital in China. Methods: A total of 36 ESBL-producing E. coli isolates were collected from body fluid samples from a Chinese district hospital. All isolates were subjected to whole genome sequencing to identify their antimicrobial resistance genes, virulence genes, serotypes, sequence types, and phylogenetic relationships by BacWGSTdb 2.0 webserver. Results: Among these isolates, all were resistant to cefazolin, cefotaxime, ceftriaxone, ampicillin, 24 (66.7%) were resistant to aztreonam, 16 (44.4%) were resistant to cefepime, and 15 were resistant (41.7%) to ceftazidime. The blaCTX-M gene was detected in all ESBL-producing E. coli isolates. Two isolates carrying two different types of blaCTX-M genes simultaneously. The carbapenem resistance gene blaKPC-2 was detected in one (2.8%) isolate. A total of 17 sequence types (STs) were found, with ST131 accounting for the majority (n =13; 36.1%). The most common serotype was O16:H5 associated with seven ST131 strains, followed by O25:H4/ST131 (n = 5) and O75:H5/ST1193 (n = 5). Evaluation of clonal relatedness revealed that all blaCTX-M gene-carrying E. coli had a difference of SNPs range from 7 to 79,198, which could be divided into four clusters. Only 7 SNPs could be found between EC266 and EC622, indicating that they are variants of the same clonal lineage. Conclusion: This study investigated the genomic characteristics of ESBL-producing E. coli isolates recovered from a district hospital in China. Continuous surveillance of ESBL-producing E. coli infections is imperative to create efficient strategies for controlling the transmission of these multi-drug resistant bacteria in clinical and community settings.

Genomic Characteristics of a Multidrug-Resistant ST648 Escherichia coli Isolate Co-Carrying blaKPC-2 and blaCTX-M-15 Genes Recovered from a Respiratory Infection in China.

Background: The transmission of carbapenem-resistant Enterobacterales pose a significant threat to global public health, which weakens the effectiveness of most antimicrobial agents. The aim of this study is to present the genomic characteristics of a multidrug-resistant Escherichia coli, which contains both blaKPC-2 and blaCTX-M-15 genes, discovered from a respiratory infection in China. Methods: The antimicrobial susceptibility of E. coli isolate 488 was measured by using the broth microdilution method. The Oxford Nanopore MinION and Illumina NovaSeq 6000 platforms were applied to determine the whole-genome sequence of this isolate. De novo assembly of short Illumina reads and long MinION reads were performed by Unicycler. In silico multilocus sequence typing (MLST), antimicrobial resistance genes and plasmid replicon types were determined using the genome sequencing data. Additionally, a pairwise core genome single nucleotide polymorphism (cgSNP) comparison between E. coli 488 and all ST648 E. coli strains retrieved from NCBI GenBank database were conducted using the BacWGSTdb 2.0 server. Results: E. coli 488 was resistant to aztreonam, levofloxacin, cefepime, fosfomycin, amikacin, imipenem, cefotaxime, and meropenem. The complete genome sequence of E. coli 488 (belong to ST648) is made up of eleven contigs totaling 5,573,915 bp, including one chromosome and ten plasmids. Eight antimicrobial resistance genes were identified, including blaKPC-2 located in a 46,161 bp IncI1-type plasmid and the blaCTX-M-15 gene situated in the chromosome. Other two E. coli S617-2 and R616-1 isolates, recovered from China in 2018, are the closest relatives of E. coli 488, with only 52 SNPs difference. The genome also contains at least 57 genomic islands and several IS elements. Conclusion: Our study reveals the first ST648 E. coli isolate containing both blaKPC-2 and blaCTX-M-15 in China. These results could provide valuable insights into the genetic characteristics, antimicrobial resistance mechanisms, and transmission dynamics of carbapenem-resistant Enterobacterales in clinical settings.

Photosensitizer-Loaded Multifunctional Chitosan Nanoparticles for Simultaneous in Situ Imaging, Highly Efficient Bacterial Biofilm Eradication, and Tumor Ablation.

In recent decades, bacterial and viral infections and chronic inflammatory response have emerged as important causes of cancer. Also, infections remain a significant cause of morbidity and mortality in cancer patients. In this work, carboxymethyl chitosan nanoparticles (CMC NPs) were synthesized in a facile and green way and further combined with ammonium methylbenzene blue (MB) as a cross-linking agent as well as a fluorescent molecule and a photosensitizer for self-imaging photodynamic therapy (PDT). The obtained CMC-MB NPs exhibited an apparent pH-responsive release behavior of MB, which was released for a prolonged period in a simulated physiological environment (pH 7.4) for more than 15 days and the time reduced to only 3.5 h in acidic conditions (pH 5.5). When irradiated by a 650 nm laser at 202 mW/cm2 for 5 min, the CMC-MB NPs showed efficient bactericidal and biofilm eradication properties as well as suppression of tumor cell growth in a similar acidified microenvironment. Furthermore, in an in vivo rabbit wound bacterial infection model, the rapid sterilization of CMC-MB NPs played a crucial role in bacterial infections, inflammation inhibition, and wound healing. As a PDT treatment against cancer, the CMC-MB NPs also exhibited an efficient antitumor therapeutic effect in a subcutaneous tumor mice model.

Design of smart targeted and responsive drug delivery systems with enhanced antibacterial properties.

The use of antibiotics has been an epoch-making invention in the past few decades for the treatment of infectious diseases. However, the intravenous injection of antibiotics lacking responsiveness and targeting properties has led to low drug utilization and high cytotoxicity. More importantly, it has also caused the development and spread of drug-resistant bacteria due to repeated medication and increased dosage. The differences in the microenvironments of the bacterial infection sites and normal tissues, such as lower pH, high expression of some special enzymes, hydrogen peroxide and released toxins, etc., are usually used for targeted and controlled drug delivery. In addition, bacterial surface charges, antigens and the surface structures of bacterial cell walls are all different from normal tissue cells. Based on the special bacterial infection microenvironments and bacteria surface properties, a series of drug delivery systems has been constructed for highly efficient drug release. This review summarizes the recent progress in targeted and responsive drug delivery systems for enhanced antibacterial properties.