Antibiotic resistance is a significant crisis that threatens human health and safety worldwide. There is an urgent need for new strategies to control multidrug-resistant (MDR) bacterial infections. The latest breakthrough in gene-editing tools based on CRISPR/Cas9 has potential application in combating MDR bacterial infections because of their high targeting ability to specifically disrupt the drug resistance genes that microbes use for infection or to kill the pathogen directly. Despite the potential that CRISPR/Cas9 showed, its further utilization has been hampered by undesirable delivery efficiency in vivo. Nanotechnology offers an alternative way to overcome the shortcomings of traditional delivery methods of therapeutic agents. Advances in nanotechnology can improve the efficacy and safety of CRISPR/Cas9 components by using customized nanoparticle delivery systems. The combination of CRISPR/Cas9 and nanotechnology has the potential to open new avenues in the therapy of MDR bacterial infections. This review describes the recent advances related to CRISPR/Cas9 and nanoparticles for antimicrobial therapy and gene delivery, including the improvement in the packaging and localizing efficiency of the CRISPR/Cas9 components in the NP (nanoparticle)/CRISPR system. We pay particular attention to the strengths and limitations of the nanotechnology-based CRISPR/Cas9 delivery system to fight nosocomial pathogens.We highlight the need for more scientific research to explore the combinatorial efficacy of various nanoparticles and CRISPR technology to control and prevent antimicrobial resistance.

The emergence of carbapenem-resistant Enterobacteriaceae strains has posed a severe threat to public health in recent years. The mobile elements carrying the New Delhi metallo-β-lactqtamase (NDM) gene have been regarded as the major mechanism leading to the rapid increase of carbapenem-resistant Enterobacteriaceae strains isolated from clinics and animals. We describe an NDM-5-producing Escherichia coli strain, ECCRA-119 (sequence type 156 [ST156]), isolated from a poultry farm in Zhejiang, China. ECCRA-119 is a multidrug-resistant (MDR) isolate that exhibited resistance to 27 antimicrobial compounds, including imipenem and meropenem, as detected by antimicrobial susceptibility testing (AST). The complete genome sequence of the ECCRA-119 isolate was also obtained using the PacBio RS II platform. Eleven acquired resistance genes were identified in the chromosome; four were detected in plasmid pTB201, while six were detected in plasmid pTB202. Importantly, the carbapenem-resistant gene blaNDM-5 was detected in the IncX3 plasmid pTB203. In addition, seven virulence genes and one metal-resistance gene were also detected. The results of conjugation experiments and the transfer regions identification indicated that the blaNDM-5-harboring plasmid pTB203 could be transferred between E. coli strains. The results reflected the severe bacterial resistance in a poultry farm in Zhejiang province and increased our understanding of the presence and transmission of the blaNDM-5 gene.

We retrospectively analyzed the effect of tigecycline and cefoperazone/sulbactam therapies on the prognosis of patients with carbapenem-resistant Acinetobacter baumannii bloodstream infection (CRAB-BSI). CRAB-BSI patients receiving tigecycline therapy or cefoperazone/sulbactam therapy between January 2012 and December 2017 was enrolled, and strict exclusion criteria were followed. The 28-day mortality of patients was analyzed. The impact of cefoperazone/sulbactam therapy on prognosis was evaluated using Cox multivariate regression analysis. The 28-day mortality of patients receiving cefoperazone/sulbactam monotherapy and cefoperazone/sulbactam-based combination therapy was also compared. Three hundred forty eight patients with CRAB-BSI were enrolled in the study. Two hundred ten patients were included after applying the exclusion criteria. Of these, 135 patients received tigecycline therapy and 75 patients received cefoperazone/sulbactam therapy. The 28-day mortality of patients in the latter group was, significantly lower than that of the tigecycline group [29.3% vs. 51.9%; P = 0.001]. Cox multivariate regression analysis revealed that cefoperazone/sulbactam therapy exerted a protective effect on the prognosis of patients [hazard ratio 0.566, 95% confidence interval (0.342–0.940); P = 0.028]. Kaplan-Meier survival curve analysis indicated that the 28-day mortality of patients receiving cefoperazone/sulbactam therapy was lower than that of patients receiving cefoperazone/sulbactam monotherapy, but the difference was not significant (22.2% vs. 40%; P = 0.074). However, the mortality of patients receiving cefoperazone/sulbactam with imipenem/cilastatin was significantly lower than that of patients receiving cefoperazone/sulbactam monotherapy (P = 0.048). Patients treated with cefoperazone/sulbactam therapy had a better clinical outcome. The mortality of patients receiving cefoperazone/sulbactam with imipenem/cilastatin seems to be the lowest.

We discovered mcr-10 -harboring isolates in the “one health” approach and reported for the first time multidrug-resistant clinically threatening ST11 K. pneumoniae isolates coharboring mcr - 10 and mcr-8 genes that are resistant to polymyxins and show reduced susceptibility to tigecycline. The exhaustive screening of 941,449 bacterial genomes in the GenBank database discovered a sporadic distribution of mcr-10 -harboring isolates all around the world in a variety of sources, especially humans, which warrants close monitoring and a particular concern in clinical settings.

In recent decades, Acinetobacter baumannii has become a major global nosocomial pathogen, with bloodstream infections (BSIs) exhibiting mortality rates exceeding 60% and imposing substantial economic burdens. However, limited large-scale genomic epidemiology has hindered understanding of its population dynamics. Here, we analyzed 1506 non-repetitive BSI-causing A. baumannii isolates from 76 Chinese hospitals over a decade (2011–2021). We identified 149 sequence types (STs) and 101 K-locus types (KLs), revealing increased population diversity. International clone (IC) 2 accounted for 81.74% of isolates, with a notable shift in prevalent STs: ST208 increased while ST191 and ST195 declined, aligning with global trends. ST208 exhibited higher virulence, greater antibiotic resistance, enhanced desiccation tolerance, and more complex transmission patterns compared to ST191 and ST195. Its genomic plasticity drives its adaptation and spread. Using the high-resolution Oxford MLST scheme, this study uncovered greater diversity and genetic factors behind ST208’s rise. A. baumannii is evolving from a low-virulence, multidrug-resistant pathogen to a more virulent one, highlighting the urgent need to address its growing threat. These findings have critical implications for infection control and public health policies.

Bacterial heteroresistance, a phenomenon where subpopulations within a bacterial strain exhibit significantly reduced antibiotic susceptibility compared to the main population, poses a major challenge in managing infectious diseases. It is considered an intermediate stage in the evolution of bacteria towards full resistance. Heteroresistant strains often have a minimal inhibitory concentration (MIC) that appears sensitive, making detection and differentiation in clinical settings difficult. As a result, the impact on clinical outcomes is challenging to fully understand, as it often remains “hidden”. In recent years, heteroresistance has received increasing attention. However, it is still poorly understood and underappreciated. We provide an overview of the epidemiology, mechanisms, and clinical impact of heteroresistance. This review underscores the critical importance of understanding and addressing bacterial heteroresistance in the ongoing fight against antibiotic resistance and infectious diseases.