Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) and pyogenic liver abscess (PLA) due to Klebsiella pneumoniae infection can trigger life-threatening malignant consequences, however, there are few studies on the strain-associated clinical pathogenic mechanisms between VAP and PLA. A total of 266 patients consist of 129 VAP and 137 PLA were included for analysis in this study. We conducted a comprehensive survey for the two groups of K. pneumoniae isolates, including phenotypic experiments, clinical epidemiology, genomic analysis, and instrumental analysis, i.e., to obtain the genomic differential profile of K. pneumoniae strains responsible for two distinct infection outcomes. We found that PLA group had a propensity for specific underlying diseases, especially diabetes and cholelithiasis. The resistance level of VAP was significantly higher than that of PLA (78.57% vs. 36%, P < 0.001), while the virulence results were opposite. There were also some differences in key signaling pathways of biochemical processes between the two groups. The combination of iucA, rmpA, hypermucoviscous phenotype, and ST23 presented in K. pneumoniae infection is more important and highly prudent for timely treatment. The present study may contribute a benchmark for the K. pneumoniae clinical screening, epidemiological surveillance, and effective therapeutic strategies.

Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer.

Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m6A modification on FDX1 mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly improves the therapeutic efficacy of the copper ionophore- elesclomol. Combining elesclomol with AGK2, a SIRT2-specific inhibitor, induce cuproptosis in gastric tumors in vitro and in vivo. These results reveal the significance of non-histone protein METTL16 lactylation on cuproptosis in tumors. Given the high copper and lactate concentrations in GC, cuproptosis induction becomes a promising therapeutic strategy for GC.

Enriched environment during adolescence modulates lipid metabolism and emotion-related behaviors in mice.

Enriched environment (EE) is an important animal experimental paradigm to decipher gene-environment interaction. It is thought to be efficient in aiding recovery from certain metabolism disorders or cognitive impairments. Recently, the effects of EE during adolescence in mice gradually draw much attention. We first established an EE model in adolescent mice, dissected lipid metabolism, and further examined baseline level of anxiety and depression by multiple behavioral tests, including open field test (OFT), elevated zero maze (EZM), tail suspension test (TST), and forced swimming test (FST). EE mice exhibited lower weights, lower cholesterol than standard housing (SH) mice. Behaviorally, EE mice traveled more distance and had higher velocity than SH mice in OFT and EZM. Besides, EE mice showed reduced anxiety levels in OFT and EZM. Furthermore, EE mice also had less immobility time than SH mice in TST and FST. Thus, these results suggest that EE during adolescence has metabolic and behavioral benefits in mice.

Insights Into the Impact of Small RNA SprC on the Metabolism and Virulence of Staphylococcus aureus.

Aim: Our previous proteomic analysis showed that small RNA SprC (one of the small pathogenicity island RNAs) of Staphylococcus aureus possesses the ability to regulate the expression of multiple bacterial proteins. In this study, our objective was to further provide insights into the regulatory role of SprC in gene transcription and metabolism of S. aureus. Methods: Gene expression profiles were obtained from S. aureus N315 wild-type and its sprC deletion mutant strains by RNA-sequencing (RNA-seq), and differentially expressed genes (DEGs) were screened by R language with a |log2(fold change)| ≥1 and a false discovery rate (FDR) ≤ 0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to understand the significance of the DEGs. The quality of RNA-seq was further verified by quantitative real-time PCR (qRT-PCR), mRNA target prediction, metabolomics analysis and transcript-level expression analysis of genes of sprC complementation strain. Results: A total of 2497 transcripts were identified, of which 60 transcripts expressions in sprC knockout strain were significantly different (37 up-regulated and 23 down-regulated DEGs). GO analysis showed that the functions of these DEGs were mainly concentrated in the biological process and molecular function related to metabolism and pathogenesis, and a higher number of genes were involved in the oxidation-reduction process, catalytic activity and binding. KEGG pathways enrichment analysis demonstrated that metabolism and pathogenesis were the most affected pathways, such as metabolic pathways, biosynthesis of secondary metabolites, purine metabolism, fructose and mannose metabolism and S. aureus infection. The qRT-PCR results of the DEGs with defined functions in the sprC deletion and complementation strains were in general agreement with those obtained by RNA-seq. Metabolomics analysis revealed 77 specific pathways involving metabolic pathways. Among them, many, such as metabolic pathways, biosynthesis of secondary metabolites and purine metabolism, were consistent with those enriched in the RNA-seq analysis. Conclusion: This study offered valuable and reliable information about the regulatory roles of SprC in S. aureus biology through transcriptomics and metabolomics analysis. These results may provide clues for new potential targets for anti-virulence adjuvant therapy on S. aureus infection.

Highly Active and Stable Fe/Co/N Co-doped Carbon-Anchored Pd Nanoparticles for Oxygen Reduction Reaction.

A highly active and stable electrocatalyst based on Pd nanoparticles anchored on zeolitic imidazolate framework-derived Fe/Co/N co-doped carbon (Pd/FeCoNC) is prepared. FeCo alloy nanoparticles are uniformly dispersed and wrapped by graphene layers in Fe/Co/N co-doped carbon (FeCoNC). The influences of carbonization temperature on the structure and catalytic activity of FeCoNC toward oxygen reduction reaction (ORR) are investigated. The FeCoNC prepared at 800 °C (FeCoNC-800) has a favorable ORR catalytic activity as a consequence of the synergistic effect of Fe/Co/N co-doping and hierarchical pore structures of coexisting micropores and mesopores. Pyridinic N in FeCoNC is a preferential adsorption site for anchoring Pd nanoparticles. Pd/FeCoNC exhibits both superior activity and durability to 40 wt % Pt/C at the same level of metallic mass loading, which shows a 44 mV higher half-wave potential (0.88 V) than Pt/C and a 91% remaining current of the initial after 10,000 s. The Fe/Co/N co-doping and hierarchical pores of FeCoNC contribute a large diffusion current, and the introduction of Pd realizes more positive onset and half-wave potentials. This work provides an easy way for preparing low-cost and high-efficiency catalysts for ORR.

JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range.

Phage therapy represents a possible treatment option to cure infections caused by multidrug-resistant bacteria, including methicillin and vancomycin-resistant Staphylococcus aureus, to which most antibiotics have become ineffective. In the present study, we report the isolation and complete characterization of a novel phage named JD219 exhibiting a broad host range able to infect 61 of 138 clinical strains of S. aureus tested, which included MRSA strains as well. The phage JD419 exhibits a unique morphology with an elongated capsid and a flexible tail. To evaluate the potential of JD419 to be used as a therapeutic phage, we tested the ability of the phage particles to remain infectious after treatment exceeding physiological pH or temperature. The activity was retained at pH values of 6.0-8.0 and below 50°C. As phages can contain virulence genes, JD419's complete genome was sequenced. The 45509 bp genome is predicted to contain 65 ORFs, none of which show homology to any known virulence or antibiotic resistance genes. Genome analysis indicates that JD419 is a temperate phage, despite observing rapid replication and lysis of host strains. Following the recent advances in synthetic biology, JD419 can be modified by gene engineering to remove prophage-related genes, preventing potential lysogeny, in order to be deployed as a therapeutic phage.

Ultrasonic-assisted synthesis of two dimensional coral-like Pd nanosheets supported on reduced graphene oxide for enhanced electrocatalytic performance.

Two dimensional (2D) Pd nanosheets supported on reduced graphene oxide (Pd/rGO) were prepared through a sonochemical routine induced by cetyltrimethylammonium bromide (CTAB). Coral-like porous Pd nanosheets (Pd/rGO-u) were obtained under the sonication condition (25 kHz, 600 W, ultrasonic transducer), while square Pd nanosheets (Pd/rGO-c) were produced via traditional chemical reduction. The size of Pd nanosheets of Pd/rGO-u and Pd/rGO-c are 69.7 nm and 59.7 nm, and the thickness are 4.6 nm and 4.4 nm, respectively. The carrier GO was proved to be partially reduced to rGO with good electrical conductivity and oxygen-containing groups facilitated a good dispersion of Pd nanosheets. The interaction between GO and CTAB made the alkyl chain assembles to a 2D lamella micelles which limit the growth of Pd atoms resulting in the formation of 2D nanosheets. A high ultrasonic power promotes the reduction and the formation of porous structure. Additionally, Pd/rGO-u exhibited a favorable electrocatalytic performance toward oxygen reduction reaction (ORR) in alkaline condition, which provided a potential synthetic strategy assisted by sonication for high-performance 2D materials.

Prevalence and molecular characterization of methicillin-resistant Staphylococcus aureus with mupirocin, fusidic acid and/or retapamulin resistance.

BACKGROUND: The data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/ALC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS: Overall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates. CONCLUSIONS: MUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.

Chronic Staphylococcus aureus Superantigen Toxic Shock Syndrome Toxin-1 Exposure Accelerates the Progression of Atherosclerosis in Rabbits.

BACKGROUND: It has been reported that infectious agents contribute to the atherosclerotic process. However, it is unclear whether Staphylococcus aureus superantigen (SAg) toxic shock syndrome toxin-1 (TSST-1) has an effect on atherosclerosis progression. The present study was designed to investigate the pathogenic role of TSST-1 exposure in the atherosclerotic process in rabbits. METHODS: New Zealand White rabbits were exposed to TSST-1 through Alzet miniosmotic pumps with a constant pumping rate. Aortic atherosclerosis was evaluated by histological and morphometric methods. Using a biochemical analyzer/enzyme-linked immunosorbent assay/immunostaining, we further analyzed various atherosclerosis-related factors. RESULTS: The gross atherosclerotic lesion area in the aortic arch increased by 15.3% in high-fat-diet rabbits exposed to TSST-1 compared to that in the control group. In the atherosclerotic lesions, TSST-1 exposure increased the content of smooth muscle cells. Moreover, TSST-1 treatment up-regulated serum tumor necrosis factor alpha (TNF-α) level, but did not affect serum lipids (except for triglycerides) and endotoxin in the rabbits. CONCLUSIONS: Our data validated that chronic stimulation with TSST-1 facilitates the progression of atherosclerosis in rabbits independently of endotoxins, indicating that S. aureus and its SAgs may be targets to prevent and treat atherosclerosis.

Exploring the whole standard operating procedure for phage therapy in clinical practice.

We have entered the post-antibiotic era. Phage therapy has recently been given renewed attention because bacteriophages are easily available and can kill bacteria. Many reports have demonstrated successful phage treatment of bacterial infection, whereas some studies have shown that phage therapy is not as effective as expected. In general, establishment of a standard operating procedure will ensure the success of phage therapy. In this paper, the whole operating procedure for phage therapy in clinical practice is explored and analyzed to comprehensively understand the success of using phage for the treatment of bacterial infectious disease in the future. The procedure includes the following: enrollment of patients for phage therapy; establishment of phage libraries; pathogenic bacterial isolation and identification; screening for effective phages against pathogenic bacteria; phage formulation preparation; phage preparation administration strategy and route; monitoring the efficacy of phage therapy; and detection of the emergence of phage-resistant strains. Finally, we outline the whole standard operating procedure for phage therapy in clinical practice. It is believed that phage therapy will be used successfully, especially in personalized medicine for the treatment of bacterial infectious diseases. Hopefully, this procedure will provide support for the entry of phage therapy into the clinic as soon as possible.

Prevention of Dermal Abscess Formation Caused by Staphylococcus aureus Using Phage JD007 in Nude Mice.

Aim: In this study, Staphylococcus phage JD007 bactericidal activity and induced immune responses during treatment were assessed in a dermal abscess model. Materials and Methods: Dermal abscesses in nude mice were established by injecting a clinical isolate of S. aureus SA325 isolated from the back under-dermal abscess of an in-patient. Results: Phage JD007 was able to inhibit the growth of S. aureus SA325 at MOI = 1 or 10, significantly preventing the formation of dermal abscesses. Moderate immune responses were observed in the prevention group through detection of cytokines. Conclusion: Phage JD007 inhibits the formation of dermal abscesses caused by a clinical S. aureus strain in nude mice without robust immune responses.

A Phage Lysin Fused to a Cell-Penetrating Peptide Kills Intracellular Methicillin-Resistant Staphylococcus aureus in Keratinocytes and Has Potential as a Treatment for Skin Infections in Mice.

Staphylococcus aureus is the main pathogen that causes skin and skin structure infections and is able to survive and persist in keratinocytes of the epidermis. Since the evolution of multidrug-resistant bacteria, the use of phages and their lysins has presented a promising alternative approach to treatment. In this study, a cell wall hydrolase (also called lysin) derived from Staphylococcus phage JD007 (JDlys) was identified. JDlys showed strong lytic activity against methicillin-resistant Staphylococcus aureus (MRSA) strains from different sources and of different multilocus sequence typing (MLST) types. Furthermore, a fusion protein consisting of a cell-penetrating peptide derived from the trans-activating transcription (Tat) factor fused to JDlys (CPPTat-JDlys) was used to kill MRSA bacteria causing intracellular infections. CPPTat-JDlys, in which the fusion of CPPTat to JDlys had almost no effect on the bacteriolytic activity of JDlys, was able to effectively eliminate intracellular MRSA bacteria and alleviate the inflammatory response and cell damage caused by MRSA. Specifically, CPPTat-JDlys was able to combat MRSA-induced murine skin infections and, consequently, expedite the healing of cutaneous abscesses. These data suggest that the novel antimicrobial CPP-JDlys may be a worthwhile candidate as a treatment for skin and skin structure infections caused by MRSA.IMPORTANCES. aureus is the main cause of skin and skin structure infections due to its ability to invade and survive in the epithelial barrier. Due to the overuse of antibiotics in humans and animals, S. aureus has shown a high capacity for acquiring and accumulating mechanisms of resistance to antibiotics. Moreover, most antibiotics are usually limited in their ability to overcome the intracellular persistence of bacteria causing skin and skin structure infections. So, it is critical to seek a novel antimicrobial agent to eradicate intracellular S. aureus In this study, a cell-penetrating peptide fused to lysin (CPP-JDlys) was engineered. Our results show that CPP-JDlys can enter keratinocytes and effectively eliminate intracellular MRSA. Meanwhile, experiments with mice revealed that CPP-JDlys efficiently inhibits the proliferation of MRSA in murine skin and thus shortens the course of wound healing. Our results indicate that the CPP-fused lysin has potential for use for the treatment of skin infections caused by MRSA.

The chemokine receptor CCR1 is identified in mast cell-derived exosomes.

Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database. Biochemical pathways were analyzed by Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the online tool DAVID. DEGs-associated protein-protein interaction networks (PPIs) were constructed using the STRING database and Cytoscape software. The genes identified from these bioinformatics analyses were verified by qRT-PCR and Western blot in mast cells and exosomes. We identified 2121 DEGs (843 up and 1278 down-regulated genes) in HMC-1 cell-derived exosomes and HMC-1 cells. The up-regulated DEGs were classified into two significant modules. The chemokine receptor CCR1 was screened as a hub gene and enriched in cytokine-mediated signaling pathway in module one. Seven genes, including CCR1, CD9, KIT, TGFBR1, TLR9, TPSAB1 and TPSB2 were screened and validated through qRT-PCR analysis. We have achieved a comprehensive view of the pivotal genes and pathways in mast cells and exosomes and identified CCR1 as a hub gene in mast cell-derived exosomes. Our results provide novel clues with respect to the biological processes through which mast cell-derived exosomes modulate immune responses.

Bio-synthesis of palladium nanocubes and their electrocatalytic properties.

The bio-synthesis of palladium nanocubes (PdNCs) was realised using pine needle extract as the reducing agent and cetyl trimethyl ammonium bromide as the capping agent. As an eco-friendly and readily available biomass, pine needle extract avoided the use of highly polluting chemical reducing agents. The growth process of PdNCs was analysed using ultraviolet-vis and Fourier transform infrared spectroscopy. Flavonoids, esters, terpenoids and polyhydric alcohols, which contain reductive groups, were mainly responsible for the transition of Pd2+ ions to PdNCs. The morphology and structure of PdNCs were characterised using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction and X-ray diffraction. It was indicated that the as-prepared PdNCs displayed a relatively high purity and good crystallinity with a face-centred cubic structure and exhibited sizes ranging from 6.11 to 29.51 nm with an average particle size of 11.18 nm. In the methanol electro-oxidation reaction, the PdNCs enclosed by {100} facets exhibited superior electro-catalytic activity to commercial Pd/C, which was rarely reported in other bio-synthesis processes for Pd catalysts. Meanwhile, the PdNCs showed excellent anti-poisoning ability and long-term stability. This study reveals the possibility of preparing shape-controlled PdNCs with a specific structure and excellent electro-catalytic activity.

Reference intervals for stone risk factors in 24-h urine among healthy adults of the Han population in China.

BACKGROUND: The aim of the study was to establish reference intervals for 24-h urinary stone risk factors in the healthy Chinese Han population. METHODS: From May 2013 to July 2014, we collected and analyzed 24-h urine samples from healthy adult Han population during a cross-sectional study across China. The protocol for analysis of 24-h urine included volume, pH, oxalate, citrate, sodium, potassium, chloride, calcium, phosphorous, creatinine, urate, magnesium, the ion activity products of calcium oxalate (AP(CaOx) indexs) and calcium phosphate (AP(CaP) indexs). We calculated the reference intervals according to the Clinical and Laboratory Standards Institute (CLSI) 2008 guidelines and compared them with those recorded in other studies. RESULTS: A total of 132 male and 123 female healthy subjects with a mean (SD, range) age of 52.4 (15.2, 19-89) years were eligible in the final analysis. Men had higher 24-h excretion of creatinine, calcium, urate and phosphorus and lower levels of citrate, magnesium, chloride, sodium and potassium than women. AP(CaOx) indexs and AP(CaP) indexs were significantly higher among men than women. When urinary findings were compared with the reference intervals, most of our data showed a high abnormality rate, especially for creatinine, calcium, citrate, magnesium, chloride, sodium and potassium. CONCLUSIONS: The present study revealed the normal metabolic status for stone risk factors of the Chinese Han population. It is therefore necessary for each country or region to define their own reference intervals for comparison of stone risk factors between patients and healthy subjects.

Isobaric tags for relative and absolute quantitation proteomics analysis of gene regulation by SprC in Staphylococcus aureus.

AIM: To explore the complete gene networks regulated by small RNA SprC and its targets in Staphylococcus aureus. MATERIALS & METHODS: The isobaric tags for relative and absolute quantitation and bioinformatic methods were utilized to identify and analyze the target proteins affected by SprC in S. aureus N315. RESULTS: Proteomic analysis showed that the expression of 44 proteins was modulated by SprC. Further, bioinformatic analysis displayed that these affected proteins mainly associated with metabolic and cellular process, biological regulation and catalytic activity. CONCLUSION: Our data provide a rich resource of SprC targets in S. aureus, although the mechanism of regulation by SprC is yet to be elucidated.

A Comprehensive Epidemiological Research for Clinical Vibrio parahaemolyticus in Shanghai.

Vibrio parahaemolyticus is one of the most important pathogen for seafood-borne gastroenteritis in Shanghai and the rest of the world. A total of 42 V. parahaemolyticus strains were isolated from 1900 fecal specimens collected from patients in Shanghai hospital presenting from January 2014 to December 2015. All isolates were evaluated for potential virulence factors [tdh, trh, and type three secretion system (T3SS) genes], typed using multilocus sequence typing (MLST) and screened for antimicrobial resistance phenotype and genotype. And for the first time, the relationship between virulence, genetic diversity and antimicrobial resistance of these isolates were identified. The results showed that 37 isolates carried the tdh gene (88.1%) and only seven isolates were positive for the trh gene. The T3SS1 and T3SS2 genes were detected in all strains and only trh-positive isolates are also containing the T3SS2ß genes. MLST analysis of the 42 Shanghai isolates identified 20 sequence types (STs) with 16 novel STs and that these clinical V. parahaemolyticus strains showed high degrees of genetic diversity. All isolates expressed high levels of resistance against Ampicillin (100.0%), Streptomycin (100.0%), Cephazolin (92.9%), Kanamycin (92.8%) and Amikacin (90.5%), and eight out of 38 resistance genes (SHV, tet(B), strA, qnrA, gryA, qnrB, sulI, sulII) were detected in at least two isolates. This study confirms that antimicrobial resistance of clinical V. parahaemolyticus isolates is greater than those of environmental isolates. Furthermore, no clear correlation between antimicrobial resistance and virulence or genetic diversity was found in this study. These results add to epidemiological data of clinical V. parahaemolyticus isolates in Shanghai and highlight the need for additional mechanistic studies, especially antimicrobial resistance, to reduce the burden of disease caused by this pathogen in China.

Characterization and complete genome of the virulent Myoviridae phage JD007 active against a variety of Staphylococcus aureus isolates from different hospitals in Shanghai, China.

BACKGROUND: The implementation of phage therapy is re-emerging with the increase in widespread antibiotic-resistant bacteria. METHODS: Staphylococcus phage JD007 was characterized and its complete genome sequence analysed. RESULTS: Staphylococcus phage JD007 was classified as belonging to the Myoviridae family based on its morphology, as observed by transmission electron microscopy. Its lytic activity was stable between pH 5-11 and below 42 °C; moreover, an absorbance curve showed that nearly 90% of the viral particles had adsorbed to its host after a 20 min co-incubation. The complete genome size is 141,836 bp, making JD007 one of the largest Staphylococcus phages of Myoviridae. No identifiable resistance or virulence genes were found in the JD007 genome. JD007 was able to lyse 95% of S. aureus isolates, including the prevalent ST239-MRSA and ST59-MRSA strains isolated from different hospitals in Shanghai, China, and inhibition assays showed that JD007 could inhibit S. aureus growth at a multiplicity of infection of 0.1. CONCLUSIONS: The results suggested that Staphylococcus phage JD007 can potentially be used in phage therapy or for the detection of S. aureus.