As antimicrobial resistance emerges as a critical global health threat, food-grade bacteriocin, a kind of antimicrobial peptide (AMPs), offers promising new therapies but is hampered by poor stability and water solubility. To address this, we engineered a carrier-free self-assembly strategy: a novel bacteriocin from lactic acid bacteria in fermented food was modified to increase its hydrophobicity, enabling spontaneous formation of nano-antimicrobial bacteriocins (NAMBs) in TSB, LB, and MH media. These NAMBs exhibit a broader antimicrobial spectrum and enhanced potency against both Gram-positive and Gram-negative pathogens, including Listeria monocytogenes, Acinetobacter baumannii, and Vibrio parahaemolyticus, as evidenced by markedly reduced minimum inhibitory concentrations in vitro and superior therapeutic efficacy in infected mice in vivo. Mechanistic investigations reveal targeted disruption of cell envelope metabolism: in L. monocytogenes, NAMBs fortify the peptidoglycan layer while depleting wall teichoic acids and lipoteichoic acids, impairing carbohydrate metabolism and membrane transport; in A. baumannii, they downregulate fatty acid synthesis, disorder phospholipid composition, and weaken lipopolysaccharide integrity, culminating in membrane destabilization and cell death. These dual actions-disordering metabolic processes and remodeling bacterial cell walls or membranes-highlight the versatility of NAMBs. Our carrier-free self-assembly approach thus overcomes AMP stability and solubility limitations and paves the way for next-generation antimicrobial therapies.

Introduction Non-typhoidal Salmonella (NTS) is a significant bacterial pathogen causing foodborne diseases, with the potential for severe bloodstream infections (BSI) leading to complications such as sepsis and high mortality rates, particularly in vulnerable populations. The rise of BSI associated NTS strains, notably ST11 S. Enteritidis, has raised public health concerns. Objectives This study aimed to investigate the epidemiological and genetic characteristics of Salmonella BSI strains in China, focusing on the adaptation of ST11 S. Enteritidis from animal and food sources to clinical settings, and to analyze correlations between clinical data and genetic profiles. Methods A total of 120 non-duplicated NTS strains isolated from bacteremia patients across nine hospitals in China between 2017 and 2022 were investigated using antimicrobial susceptibility testing, whole-genome sequencing and bioinformatics analysis. Results The average annual prevalence of bloodstream infections (BSI) due to Salmonella remained stable at 0.77%, based on 31,177 positive blood cultures, with 96.8% of infections caused by NTS strains, primarily Salmonella enterica serovar Enteritidis (41.9%) and Typhimurium variants (16.1%). WGS results revealed significant genetic features, including mutations and multiple copies of the 5S rRNA gene, which were identified as key drivers for host adaptation and systemic dissemination, particularly in immunocompetent adults. Notably, 40% of foodborne strains carried these genetic traits, exhibiting a higher genomic potential for invasiveness compared to animal-derived strains within this specific dataset. Additionally, we demonstrated the resistance levels of BSI Salmonella to first-line antibiotics and identified a novel plasmid that mediates the co-transmission of cefotaxime resistance and virulence factors, complicating treatment options. These factors significantly contribute to the transition of diarrheagenic strains to types with an enhanced potential for bloodstream invasion. Conclusion These findings underscore the ongoing public health concern associated with NTS infections and highlight the need for continuous surveillance and effective intervention strategies to manage these emerging threats.

Pseudomonas aeruginosa is a significant opportunistic pathogen, particularly prevalent in intensive care units (ICUs). Through a comprehensive genomic and phenotypic analysis of 518 ICU and healthy isolates collected over a 13-year period (2010-2022), we found that ICU strains, despite reduced sequence type (ST) diversity, are dominated by persistent high-risk clones, notably ST463 and ST1076. Despite possessing a lower overall prophage content, ICU isolates show a broader and more diverse repertoire of anti-phage defense systems. This strengthened defense capacity correlates with ICU strains, demonstrating heightened resistance to phage challenge and contributing to lower historical phage exposure. Concurrently, ICU isolates harbor a significantly higher antimicrobial resistance (AMR) gene burden. Our detailed genomic analysis shows that this increased AMR is primarily driven by plasmid acquisition. Importantly, AMR genes associated with prophage elements are exclusively found in ICU isolates, highlighting their selective retention and functional contribution to resistance in this high-pressure environment. Furthermore, specific virulence genes, including exoU, pilA, and rhsP2, are more prevalent in ICU strains, indicating enhanced pathogenicity. Collectively, these findings underscore a qualitative distinction in ICU P. aeruginosa: their dominance and persistence stem from highly adapted clones, robust anti-phage defenses, rapid plasmid-mediated AMR acquisition, and clinically selected prophage-borne AMR.

The emergence and rapid dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) pose a serious threat to public health. Antibiotic treatment failure of K. pneumoniae infections has been largely attributed to acquisition of antibiotic resistance and bacterial biofilm caused by the presence of antibiotic persisters. There is an urgent need for novel antimicrobial agents or therapy strategies to manage infections caused by these notorious pathogens. In this study, we screened a collection of compounds that can dissipate bacterial proton motive force (PMF) and intermediate metabolites that can suppress antibiotic tolerance, and identified an antifungal drug sulconazole which can act in combination with glucose or trehalose to exert strong antibacterial effect against starvation-induced CR-hvKP persisters. Investigation of underlying mechanisms showed that sulconazole alone caused dissipation of transmembrane PMF, and sulconazole used in combination with glucose or trehalose could significantly inhibit the efflux activity, reduce NADH and ATP levels, and cause intracellular accumulation of reactive oxygen species (ROS) in CR-hvKP persisters, eventually resulting in bacterial cell death. These findings suggest that the sulconazole and glucose/trehalose combination is highly effective in eradicating multidrug-resistant and hypervirulent K. pneumoniae persisters, and may be used in development of a feasible strategy for treatment of chronic and recurrent K. pneumoniae infections.

Carbapenem-resistant Vibrio parahaemolyticus has emerged and spread extensively in China, posing a substantial threat to food safety and human health. This study investigated the prevalence of carbapenem resistance in V. parahaemolyticus strains recovered from various types of food samples in China, and the underlying mechanisms of transmission of the blaNDM-1 gene harbored by such strains. In this work, a total of 230 (62.1

Acinetobacter baumannii (Ab) is one of the most significant bacterial pathogens inducing hospital-acquired infections worldwide, with a high mortality rate. The continuous emergence of multidrug-resistant (MDR) phenotypes presents a significant challenge in combating Ab infections with antimicrobial drugs. In this study, we found that the type VI secretion system and the iron transportation system synergistically enhance siderophore production and further contribute to the virulence of Ab. The double knockout mutant strain, ΔhcpΔbasE, exhibited further reductions in growth rate, siderophore production under iron-deficient conditions, biofilm formation, serum resistance, cell adhesion and invasion, and cytotoxicity compared to the single knockout strains, knockout of T6SS, Δhcp or iron transportation system, ΔbasE. In vitro experiments demonstrated that these two systems work synergistically to enhance virulence, with their combined effect exceeding the additive contributions of each individual system. Consistently, the ΔhcpΔbasE strain failed to cause mortality in the mouse model, even at very high inoculum levels. Further studies revealed that, compared to ATCC17978, ΔhcpΔbasE strain infection resulted in lower levels of extracellular hepcidin and intracellular iron in host cells, which correlate well with the significantly reduced ability to produce siderophores in the double knockout strain. Due to impaired iron acquisition, ΔhcpΔbasE strain became more susceptible to macrophage phagocytosis and exhibited lower survival rates in the host, leading to an inability to trigger a cytokine storm and subsequent host death. The findings of this study provide insights into the Ab pathogenesis and contribute to the development of intervention measures to control clinical Ab infections and mortality.

BACKGROUND:Development of polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a severe challenge to public health. Here we aimed to perform a retrospective study of prevalence and molecular characteristics of polymyxin-resistant CRKP strains. METHODS:4455 clinical CRKP strains from 18 provinces in China during 2000 to 2023 were collected. Polymyxin-resistant CRKP strains were subjected to antimicrobial susceptibility testing, whole genome sequencing and bioinformatic analysis. Molecular mechanisms underlying the polymyxin resistance in CRKP were analyzed. RESULTS:Here we show that polymyxin-resistant CRKP emerge initially in 2014, prevalence of such strains then increase steadily over the years, reaching a rate of 9.86% in 2023. In total, 112 polymyxin-resistant CRKP isolates are identified. Antimicrobial susceptibility tests show that all polymyxin-resistant CRKP are resistant to commonly used antibiotics, yet most isolates remain susceptible only to ceftazidime-avibactam and tigecycline. Predominant polymyxin resistance mechanism in CRKP is mutations in mgrB (59/112), which commonly involves disruption of mgrB by insertion of elements such as ISKpn26 (20/59), IS903B (14/59), and ISKpn14 (9/59). Phylogenetic analysis reveals frequent clonal dissemination of polymyxin-resistant CRKP within the same hospital and even among different hospitals in neighboring provinces. pLVPK-like virulence plasmids are detected in 46 isolates, such strains are therefore categorized as polymyxin and carbapenem-resistant hypervirulent K. pneumoniae which may cause infections with high mortality. CONCLUSIONS:Our results highlight frequent clonal transmission of polymyxin-resistant CRKP within hospitals. Continuous surveillance of polymyxin resistance among CRKP should be implemented to prevent further dissemination of such strains in clinical settings in China.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has led to a high mortality rate in the clinical setting and garnered significant attention in the clinical and scientific communities. It is still not clear which major mechanisms mediate the rapid evolution of hvKp in clinical settings since the plasmid-encoding hypervirulence phenotype is considered non-conjugative. In this study, we revealed a conjugative plasmid, p16HN200-Vir, encoding virulence-associated iuc operon (iucABCDiutA) and resulting in a hypervirulent phenotype. In silico analysis of Kp strains from NCBI predicted a total of 94 p16HN200-Vir-like conjugative virulence plasmids. These sequences were identified in 19 sequence types (STs) of the host with significant geographical variations in distribution across countries and continents. Notably, ST11 was predominant in China, while ST147 and ST395 were prominent in the United Kingdom and Russia, respectively. These plasmids could be categorized into seven lineages, some of which formed distinct geographical clusters in China and the UK, while others exhibited a hybrid population. Importantly, most of the plasmids carried different carbapenemases, including blaNDM-1/5 (lineage 6 and 7), and blaOXA-48/232 (lineage 2 and 5). Specifically, plasmids recovered from the United Kingdom and Russia were lineage-specific, with blaNDM-1 present in lineage 6 and blaNDM-5 in lineage 7. Our data suggest that this type of conjugative plasmids has spread around the world and contributed significantly to the current rapid evolution of CR-hvKp in clinical settings. Further surveillance of these types of conjugative plasmids in clinical Kp is warranted. IMPORTANCE:In this study, we found that the conjugative virulence plasmids containing carbapenem resistance genes could be conjugated to Klebsiella strains, enabling them to express antibiotic resistance and hypervirulence-associated phenotypes simultaneously. More importantly, we observed that the global dissemination of this type of multidrug resistance and hypervirulence conjugative plasmid is lineage specific. The UMAP projection revealed that the regional variations were correlated with ST types and serotypes, which poses a global threat of the CR-hvKp infection worldwide.

While the role of flies as potential vectors for bacterial transmission is well recognized, the epidemiological features and genomic characteristics of associated antimicrobial-resistant strains remain underexplored. This study conducted a nationwide surveillance including 3689 flies and 838 isolates from sixteen human communities (HCs) and eight animal farms (AFs) across 21 provinces in China. Our findings revealed high carriage rates of carbapenem-resistant Enterobacteriaceae (CRE) in flies, with 27.0 % in AFs and 15.3 % in HCs. Among the 705 CRE strains identified, Providencia spp. (n = 356) and Escherichia coli (n = 231) were predominant, with 90.6 % attributed to the dissemination of the blaNDM gene. Phylogenetic tree analysis highlighted frequent clonal transmission events, with over 18 and 13 clonal evolutionary clades in Providencia spp. and E. coli, respectively. Notably, spearman analysis linked the increase of CRE prevalence in AFs flies to environmental factors like precipitation (p < 0.028) and temperature (p < 0.037), while in HCs, it positively corelated with the total meat production (p < 0.027) in each province except for Hainan. Despite significant differences in ciprofloxacin resistance (p ≤ 0.001) among E. coli strains from HCs and AFs, core genome cluster analysis and Uniform Manifold Approximation and Projection (UMAP) approach indicated these strains exhibiting close relatedness to clinical strains. This comprehensive study underscores the critical role of flies in the escalation of CRE spread within the ecosystem in China. Flies found in both HCs and AFs contribute to the dissemination of CRE, highlighting the need for urgent interventions to address this pressing issue.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a global threat due to its high mortality in clinical patients. However, the specific mechanisms underlying this increased mortality remain unclear. The objective of this study is to investigate how the development of a resistance phenotype contributes to the significantly higher mortality associated with this pathogen. To achieve this, a collection of isogeneic strains was generated. The clinical carbapenem-susceptible K. pneumoniae (CSKP) strain HKU3 served as the control isolate, while HKU3-KPC was created through conjugation with a blaKPC-2-bearing plasmid and served as clinical CRKP strain. Using a sepsis model, it was demonstrated that both HKU3 and HKU3-KPC exhibited similar levels of virulence. Flow cytometry, RNA-seq, and ELISA analysis were employed to assess immune cell response, M1 macrophage polarization, and cytokine storm induction, revealing that both strains elicited comparable types and levels of these immune responses. Subsequently, meropenem was utilized to treat K. pneumoniae infection, and it was found that meropenem effectively reduced bacterial load, inhibited M1 macrophage polarization, and suppressed serum cytokine production during HKU3 (CSKP) infection. However, these effects were not observed in the case of HKU3-KPC (CRKP) infection. These findings provide evidence that the high mortality associated with CRKP is attributed to its enhanced survival within the host during antibiotic treatment, resulting in a cytokine storm and subsequent host death. The development of an effective therapy for CRKP infections could significantly reduce the mortality caused by this pathogen.

Background The continuous emergence of multidrug-resistant (MDR) Acinetobacter baumannii (Ab) strains poses further challenges in its control and clinical management. It is necessary to decipher the mechanisms underlying the high mortality of Ab infections to explore unconventional strategies for controlling outbreaks of drug-resistant infections. Methods The immune responses of Ab sepsis infection were investigated using flow cytometry, RNA-seq, qRT-PCR, and ELISA and scRNA-seq. The detailed pathways mediating Ab immune responses were also depicted and a specific therapy was developed based on the understanding of the mechanisms underlying Ab-induced cytokine storms. Findings The results highlighted the critical role of alveolar and interstitial macrophages as targets of Ab during the infection process. These cells were found to undergo polarization towards the M1 phenotype, triggering a cytokine storm that eventually caused the death of the host. The polarization and excessive inflammatory response mediated by macrophages were mainly regulated by the TLR2/Myd88/NF-κB signaling pathway. Suppression of Ab-triggered inflammatory responses and M1 polarization by the drug naproxen (NPXS) was shown to confer full protection of mice from lethal infections. Interpretation The findings in this work depict the major mechanisms underlying the high mortality rate of Ab infections and highlight the clinical potential application of anti-inflammatory drugs or immunosuppressants in reducing the mortality of such infections, including those caused by MDR strains. Funding Funding sources are described in the acknowledgments section.

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses grave threats to human health. These strains increased dramatically in clinical settings in China in the past few years but not in other parts of the world. Four isogenic K. pneumoniae strains, including classical K. pneumoniae, carbapenem-resistant K. pneumoniae (CRKP), hypervirulent K. pneumoniae (hvKP) and CR-hvKP, were created and subjected to phenotypic characterization, competition assays, mouse sepsis model and rat colonization tests to investigate the mechanisms underlying the widespread nature of CR-hvKP in China. Acquisition of virulence plasmid led to reduced fitness and abolishment of colonization in the gastrointestinal tract, which may explain why hvKP is not clinically prevalent after its emergence for a long time. However, tigecycline treatment facilitated the colonization of hvKP and CR-hvKP and reduced the population of Lactobacillus spp. in animal gut microbiome. Feeding with Lactobacillus spp. could significantly reduce the colonization of hvKP and CR-hvKP in the animal gastrointestinal tract. Our data implied that the clinical use of tigecycline to treat carbapenem-resistant K. pneumoniae infections facilitated the high spread of CR-hvKP in clinical settings in China and demonstrated that Lactobacillus spp. was a potential candidate for anticolonization strategy against CR-hvKP.

Objectives: Non-typhoidal Salmonella (NTS) strains, particularly when the infection progresses to become invasive and leads to bacteremia, can pose life-threatening risks to immunocompromised patients. However, there is a scarcity of information regarding the large-scale surveillance and genetic characteristics of Salmonella strains that cause bloodstream infections (BSI) in China.Methods: We performed a genome-based epidemiological study of Salmonella strains isolated from bacteremia patients in nine hospitals in China during the period 2017 to 2022. A total of 120 non-duplicated NTS strains that caused BSI were identified and subjected to phenotyping, whole-genome sequencing (WGS) and bioinformatic analysis.Results: In China, the average annual prevalence of BSI Salmonella isolates from invasive infections was almost stabilized at 0.77% from 2017 to 2022. Among which 96.8% (120/124) Salmonella bloodstream infections were caused by NTS strains, which mainly comprise Salmonella enterica serotype Enteritidis (n=52, 41.9%), Salmonella enterica serotype Typhimurium and monophasic variants (n=20, 16.1%) and Salmonella enterica serotype Goldcoast (n=8, 6.5%). Bacteremia patients from whom the Salmonella strains were recovered exhibited symptoms of infectious-bacterial fever (n=34, 28.3%), respiratory infections (n=26, 21.7%,), gastrointestinal infections (n=29, 24.2%), sepsis (n=11, 9.2%); a significant proportion of bacteremia patients were immunocompromised due to various underlying illnesses (n=24, 20.0%).Among the 120 BSI-associated NTS isolates tested, 9.1% (11/120) and 11.0% (13/120) were resistant to cefotaxime and ciprofloxacin, respectively. Notably, evolutionary events of two blaCTX-M-carrying plasmids were observed and found to result in the dissemination of cefotaxime resistance-encoding elements in S. Enteritidis. Conclusion: Findings of this work provide insight into genetic factors that underlie the potential threat that the BSI-associated NTS strains, especially those that may compromise the effectiveness of current therapeutic approaches; our data showed that monitoring of blaCTX-M-bearing S. Enteritidis is necessary.Funding: This work was supported by the grants from National Key Research and Development Program of China (No. 2022YFD1800400); Guangdong Major Project of Basic and Applied Basic Research: [Grant Number 2020B0301030005]; National Natural Science Fund in China and Research Grant Council of the Government of Hong Kong SAR: [Grant Number NSFC-RGC, N_PolyU521/18]; National Natural Science Foundation of China (No. 82102451); Zhejiang Health Science and Technology Project (grant 2021KY1109); Science and Technology Bureau of Jiaxing City (grant 2021AD30104).Declaration of Interest: The authors declare no competing interests.Ethical Approval: Ethical permission was approved by the Ethics Committee of Second Affiliated Hospital of Zhejiang University, School of Medicine, with reference No. 2022-0299.

The tigecycline resistance gene tet(X4) has been widely reported in animals and animal products in some Asian countries including China in recent years but only sporadically detected in human. In this study, we investigated the prevalence and genetic features of tet(X4)-positive clinical E. coli strains. A total of 462 fecal samples were collected from patients in four hospitals located in four provinces in China in 2023. Nine tet(X4)-positive E. coli strains were isolated and subjected to characterization of their genetic and phenotypic features by performing antimicrobial susceptibility test, whole-genome sequencing, bioinformatic and phylogenetic analysis. The majority of the test strains were found to exhibit resistance to multiple antimicrobial agents including tigecycline but remained susceptible to colistin and meropenem. A total of seven different sequence types (STs) and an unknown ST type were identified among the nine tet(X4)-positive strains. Notably, the tet(X4) gene in six out of these nine tet(X4)-positive E. coli strains was located in a IncFIA-HI1A-HI1B hybrid plasmid, which was an tet(X4)-bearing epidemic plasmid responsible for dissemination of the tet(X4) gene in China. Furthermore, the tet(X4) gene in four out of nine tet(X4)-positive E. coli isolates could be successfully transferred to E. coli EC600 through conjugation. In conclusion, this study characterized the epidemic tet(X4)-bearing plasmids and tet(X4)-associated genetic environment in clinical E. coli strains, suggested the importance of continuous surveillance of such tet(X4)-bearing plasmids to control the increasingly widespread dissemination of tigecycline-resistant pathogens in clinical settings in China.

The global transmission of carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant and grave threat to human health. To investigate the potential relationship between hospital sewage and the transmission of CRAB within healthcare facilities, isolates of Acinetobacter spp. obtained from untreated hospital sewage samples were subjected to antimicrobial susceptibility tests, genome sequencing, and bioinformatic and phylogenetic tree analysis, and that data were matched with those of the clinical isolates. Among the 70 Acinetobacter spp. sewage isolates tested, A. baumannii was the most prevalent and detectable in 5 hospitals, followed by A. nosocomialis and A. gerneri. Worryingly, 57.14 % (40/70) of the isolates were MDR, with 25.71 % (18/70) being resistant to carbapenem. When utilizing the Pasteur scheme, ST2 was the predominant type among these CRAB isolates, with Tn2006 (ΔISAba1-blaOXA-23-ATPase-yeeB-yeeA-ΔISAba1) and Tn2009 (ΔISAba1-blaOXA-23-ATPase-hp-parA-yeeC-hp-yeeB-ΔISAba1) being the key mobile genetic elements that encode carbapenem resistance. Seven A. gerneri isolates which harbored Tn2008 (ISAba1-blaOXA-23 -ATPase) and the blaPER-1 gene were also identified. Besides, an A. soil isolate was found to exhibit high-level of meropenem resistance (MIC ≥128 mg/L) and harbor a blaNDM-1 gene located in a core genetic structure of ISAba125-blaNDM-1-ble-trpF-dsbC-cutA. To investigate the genetic relatedness between isolates recovered from hospital sewage and those collected from ICUs, a phylogenetic tree was constructed for 242 clinical isolates and 9 sewage isolates. The results revealed the presence of two evolutionary clades, each containing isolates from both ICU and sewage water, suggesting that CRAB isolates in untreated sewage water were also the transmission clones or closely related evolutionary isolates recoverable in hospital settings. Findings in this work confirm that hospital sewage is a potential reservoir of CRAB.

Klebsiella pneumoniae (Kp) is increasingly recognized as a reservoir for a range of antibiotic resistance genes and a pathogen that frequently causes severe infections in both hospital and community settings. In this study, we have identified a novel mechanism of conjugative transfer of a non-conjugative virulence plasmid through the formation of a fusion plasmid between the virulence plasmid and a novel 59,162 bp IncN- plasmid. This plasmid was found to be a multidrug-resistance (MDR) plasmid and carried a T4SS cluster, which greatly facilitated the efficient horizontal transfer of the fusion plasmid between Kp strains. The fused virulence plasmid conferred the resistance of serum killing and macrophage phagocytosis to the transconjugants. Importantly, this plasmid was shown to be essential for Kp virulence in a mouse model. Mechanistic analysis revealed that the virulence factors encoded by this virulence plasmid contributed to resistance to in vivo clearance and induced a high level of proinflammatory cytokine IL-1β, which acts as an inducer for more neutrophil recruitment. The transmission of the fusion plasmid in Kp has the potential to convert it into both MDR and hypervirulent Kp, accelerating its evolution, and posing a serious threat to human health. The findings of this study provide new insights into the rapid evolution of MDR and hypervirulent Kp in recent years.

Dear Editor, Klebsiella pneumoniae(Kp)has become the most important bacterial pathogen causing high mortality rates in clinical patients due to the continuous evolution to several important variants such as carbapenem-resistant(CR-Kp),hypervirulent(hvKp)and both CR and hv K.pneumoniae(CR-hvKp).The high mortality caused by clinical hvKp is attributed to the non-response to antibiotic treatment.Therefore,a comprehensive understanding of hvKp-host interaction,especially the hvKp-mediated immune responses,is necessary.Although Kp-host interaction has been studied for more than 20 years,most research showed that pro-inflammatory signaling was crucial to Kp clearance in the host,1 without providing evidence to explain why hvKp causes a high rate of death.

BackgroundIn China, the blaNDM gene has been recovered from human bacterial isolates since 2011. After 2014, detections of this gene in animal and food bacterial isolates have increasingly been reported.AimWe aimed to understand how blaNDM-bearing bacteria could spread between humans, animals, and animal-derived food.MethodsA total of 288 non-duplicate Escherichia coli strains, including 130 blaNDM-carrying and 158 blaNDM-negative strains were collected from clinical (humans), food-producing animals (pigs) and food (retail pork) sources between 2015 and 2017. The strains were whole genome sequenced. Core-genome-multilocus-sequence-typing was conducted. To investigate if sequence types (STs) found in human, animal or food samples could have a prior origin in a clinical, animal or food-borne animal reservoir, discriminant analysis of principal components (DAPC) was used. Plasmids bearing blaNDM were characterised.ResultsThe 130 blaNDM-carrying E. coli strains comprised a total of 60 STs, with ST167 (10/51), ST77 (6/33) and ST48 (6/46) being most prevalent in clinical, animal and food sources, respectively. Some ST10 and ST167 strains were respectively found among all three sources sampled, suggesting they might enable transfer of blaNDM between sources. DAPC analysis indicated possible transmissions of ST167 from humans to animals and ST10 from animals to human. In 114 of 130 blaNDM-carrying isolates, blaNDM was located on an IncX3 plasmid.ConclusionThis study in a Chinese context suggests that cross-species transmission of certain STs of E. coli harbouring blaNDM on mobile elements, may facilitate the spread of carbapenem-resistant Enterobacteriaceae. Stringent monitoring of blaNDM-bearing E. coli in ecosystems is important.

Salmonella Corvallis ST1541 has recently emerged as a globally disseminated pathogenic strain that often causes severe food-borne infections. Unlike most pandemic serotypes of Salmonella , the ST1541 strains harbored ColRNA1 plasmids that contain qnr -like determinants known to be responsible for the increasing incidence of ciprofloxacin-resistant food-borne Salmonella infections. In this study, we conducted a genomic analysis of a global collection of 388 S. Corvallis ST1541 strains collected within a twenty-year period. We investigated the genetic characteristics of plasmid-mediated quinolone resistance (PMQR) plasmids harbored by these S. Corvallis strains, established a minimum spanning tree (MST) to determine the temporal and spatial distribution of the top 10 MST clusters, inferred a time-phylogenies for the major sub-lineages and traced the routes of international dissemination of this serotype strains. Bayesian algorithm predicted that UK might be the origin of S. Corvallis strains currently prevalent in various countries. This idea is supported by the observation of the emergence of intercontinental-disseminated clonal strains and extensive transmission of the extensive-drug resistance (XDR)-encoding plasmid pSA663. This study therefore provides valuable insight into the evolution of globally transmitted S. Corvallis strains and suggests a need to strengthen cooperation between different countries to control the dissemination of these drug-resistant bacteria.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major concern in clinical settings worldwide, yet few genetic and epidemiological studies on CRPA strains have been performed in China. Here, we sequence and analyze the genomes of 416 P. aeruginosa strains from hospitals in China to elucidate the genetic, phenotypic, and transmission characteristics of CRPA strains and to identify the molecular signatures responsible for the observed increase in the prevalence of CRPA infections in China.