Table_3_Epidemiological characteristics of SHV, cmlv, and FosA6-producing carbapenem-resistant Klebsiella pneumoniae based on whole genome sequences in Jiangsu, China.xlsx

Carbapenem-resistant Klebsiella pneumoniae (CRKP), particularly those with high virulence, cause invasive disease in clinical settings. An epidemiological investigation was conducted on the evolution, virulence, and antimicrobial resistance of CRKP isolates in two tertiary teaching hospitals in Jiangsu, China from November 2020 to December 2021. There were 31 different CRKP strains discovered. We performed whole genome sequencing (WGS) on 13 SHV, cmlv, and FosA6-producing CRKP to reveal molecular characteristics. Five ST15/ST11 isolates had CRISPR-Cas systems. By conjugation tests, KPC-2 can be transmitted horizontally to E. coil. A conjugative pHN7A8-related multi-resistance plasmid (KPC-2, blaCTX-M-65, blaTEM-1, fosA3, catII, and rmtB) was first discovered in CRKP clinical isolates. Using bacteriological testing, a serum killing assay, and an infection model with Galleria mellonella, three ST11-K64 KPC-2 generating carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) were identified. These strains harbored a virulent plasmid and an IncFII-family pKPC/pHN7A8 conjugative plasmid, which led to hypervirulence and resistance. One of these CR-hvKPs, which co-harbored KPC-2, NDM-6, SHV-182, SHV-64, and blaCTX-M-122 genes, was first discovered. Importantly, this CR-hvKP strain also produced biofilm and had non-inferior fitness. The widespread use of ceftazidime/avibactam might provide this CR-hvKP with a selective advantage; hence, immediate action is required to stop its dissemination. Another important finding is the novel ST6136 in K. pneumoniae. Finally, the sterilization efficiency rates of Fe2C nanoparticles in CRKP were more than 98%. Furthermore, our novel antibacterial Fe2C nanoparticles may also provide a therapeutic strategy for infections.</p

Table_2_Epidemiological characteristics of SHV, cmlv, and FosA6-producing carbapenem-resistant Klebsiella pneumoniae based on whole genome sequences in Jiangsu, China.xlsx

Carbapenem-resistant Klebsiella pneumoniae (CRKP), particularly those with high virulence, cause invasive disease in clinical settings. An epidemiological investigation was conducted on the evolution, virulence, and antimicrobial resistance of CRKP isolates in two tertiary teaching hospitals in Jiangsu, China from November 2020 to December 2021. There were 31 different CRKP strains discovered. We performed whole genome sequencing (WGS) on 13 SHV, cmlv, and FosA6-producing CRKP to reveal molecular characteristics. Five ST15/ST11 isolates had CRISPR-Cas systems. By conjugation tests, KPC-2 can be transmitted horizontally to E. coil. A conjugative pHN7A8-related multi-resistance plasmid (KPC-2, blaCTX-M-65, blaTEM-1, fosA3, catII, and rmtB) was first discovered in CRKP clinical isolates. Using bacteriological testing, a serum killing assay, and an infection model with Galleria mellonella, three ST11-K64 KPC-2 generating carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) were identified. These strains harbored a virulent plasmid and an IncFII-family pKPC/pHN7A8 conjugative plasmid, which led to hypervirulence and resistance. One of these CR-hvKPs, which co-harbored KPC-2, NDM-6, SHV-182, SHV-64, and blaCTX-M-122 genes, was first discovered. Importantly, this CR-hvKP strain also produced biofilm and had non-inferior fitness. The widespread use of ceftazidime/avibactam might provide this CR-hvKP with a selective advantage; hence, immediate action is required to stop its dissemination. Another important finding is the novel ST6136 in K. pneumoniae. Finally, the sterilization efficiency rates of Fe2C nanoparticles in CRKP were more than 98%. Furthermore, our novel antibacterial Fe2C nanoparticles may also provide a therapeutic strategy for infections.</p

Table_1_Epidemiological characteristics of SHV, cmlv, and FosA6-producing carbapenem-resistant Klebsiella pneumoniae based on whole genome sequences in Jiangsu, China.xlsx

Carbapenem-resistant Klebsiella pneumoniae (CRKP), particularly those with high virulence, cause invasive disease in clinical settings. An epidemiological investigation was conducted on the evolution, virulence, and antimicrobial resistance of CRKP isolates in two tertiary teaching hospitals in Jiangsu, China from November 2020 to December 2021. There were 31 different CRKP strains discovered. We performed whole genome sequencing (WGS) on 13 SHV, cmlv, and FosA6-producing CRKP to reveal molecular characteristics. Five ST15/ST11 isolates had CRISPR-Cas systems. By conjugation tests, KPC-2 can be transmitted horizontally to E. coil. A conjugative pHN7A8-related multi-resistance plasmid (KPC-2, blaCTX-M-65, blaTEM-1, fosA3, catII, and rmtB) was first discovered in CRKP clinical isolates. Using bacteriological testing, a serum killing assay, and an infection model with Galleria mellonella, three ST11-K64 KPC-2 generating carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) were identified. These strains harbored a virulent plasmid and an IncFII-family pKPC/pHN7A8 conjugative plasmid, which led to hypervirulence and resistance. One of these CR-hvKPs, which co-harbored KPC-2, NDM-6, SHV-182, SHV-64, and blaCTX-M-122 genes, was first discovered. Importantly, this CR-hvKP strain also produced biofilm and had non-inferior fitness. The widespread use of ceftazidime/avibactam might provide this CR-hvKP with a selective advantage; hence, immediate action is required to stop its dissemination. Another important finding is the novel ST6136 in K. pneumoniae. Finally, the sterilization efficiency rates of Fe2C nanoparticles in CRKP were more than 98%. Furthermore, our novel antibacterial Fe2C nanoparticles may also provide a therapeutic strategy for infections.</p

Multistimuli-Regulated Photochemothermal Cancer Therapy Remotely Controlled <i>via</i> Fe₅C₂ Nanoparticles

Stimuli-controlled drug delivery and release is of great significance in cancer therapy, making a stimuli-responsive drug carrier highly demanded. Herein, a multistimuli-controlled drug carrier was developed by coating bovine serum albumin on Fe₅C₂ nanoparticles (NPs). With a high loading of the anticancer drug doxorubicin, the nanoplatform provides a burst drug release when exposed to near-infrared (NIR) light or acidic conditions. <i>In vitro</i> experiment demonstrated a NIR-regulated cell inhibition that is ascribed from cellular uptake of the carrier and the combination of photothermal therapy and enhanced drug release. The carrier is also magnetic-field-responsive, which enables targeted drug delivery under the guidance of a magnetic field and monitors the theranostic effect by magnetic resonance imaging. <i>In vivo</i> synergistic effect demonstrates that the magnetic-driven accumulation of NPs can induce a complete tumor inhibition without appreciable side effects to the treated mice by NIR irradiation, due to the combined photochemotherapy. Our results highlight the great potential of Fe₅C₂ NPs as a remote-controlled platform for photochemothermal cancer therapy

Monodisperse Au–Fe₂C Janus Nanoparticles: An Attractive Multifunctional Material for Triple-Modal Imaging-Guided Tumor Photothermal Therapy

Imaging-guided photothermal therapy (PTT) by combination of imaging and PTT has been emerging as a promising therapeutic method for precision therapy. However, the development of multicomponent nanoplatforms with stable structures for both PTT and multiple-model imaging remains a great challenge. Herein, we synthesized monodisperse Au–Fe₂C Janus nanoparticles (JNPs) of 12 nm, which are multifunctional entities for cancer theranostics. Due to the broad absorption in the near-infrared range, Au–Fe₂C JNPs showed a significant photothermal effect with a 30.2% calculated photothermal transduction efficiency under 808 nm laser irradiation <i>in vitro</i>. Owing to their excellent optical and magnetic properties, Au–Fe₂C JNPs were demonstrated to be advantageous agents for triple-modal magnetic resonance imaging (MRI)/multispectral photoacoustic tomography (MSOT)/computed tomography (CT) both <i>in vitro</i> and <i>in vivo</i>. We found that Au–Fe₂C JNPs conjugated with the affibody (Au–Fe₂C–Z_HER2:342) have more accumulation and deeper penetration in tumor sites than nontargeting JNPs (Au–Fe₂C–PEG) <i>in vivo</i>. Meanwhile, our results verified that Au–Fe₂C–Z_HER2:342 JNPs can selectively target tumor cells with low cytotoxicity and ablate tumor tissues effectively in a mouse model. In summary, monodisperse Au–Fe₂C JNPs, used as a multifunctional nanoplatform, allow the combination of multiple-model imaging techniques and high therapeutic efficacy and have great potential for precision theranostic nanomedicines