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Previous studies have shown that livestock (LA)-MRSA ST398 evolved from a human-adapted methicillin-susceptible S. aureus (MSSA) clone. However, detailed information regarding ST9 is still unclear. Here, we characterized a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) ST9-SCCmec XII isolate that has not been previously reported to cause serious disease in China. We obtained whole-genome sequences of one ST9-t899-XII isolate—ZY462471—from a patient with bloodstream infection without livestock contact. The antibiotic susceptibilities of ZY462471 were determined and the clinical information was extracted from medical notes and compared with twenty-seven previously sequenced genomes. Phylogenetic reconstruction was performed to investigate the probable host evolutionary origins of ZY462471, and the difference in resistome and virulence factors were investigated. Virulence assay was performed to evaluate the high virulence potential of ZY462471 and compare the virulence between the closest ST9 MSSA neighbours. Clinical data suggested that ZY462471 is a CA-MRSA. Phylogenetic analysis showed a much closer relationship of ZY462471 with human-associated MSSA ST9 isolates than other LA-MRSA ST9 isolates, suggesting that ZY462471 probably evolved from ST9 MSSA predecessors by acquiring an SCCmec cassette. Importantly, virulence assays indicated that ZY462471 was highly virulent and compared with the MSSA ST9 predecessors, ZY462471 did not show attenuated virulence. Finally, we found that ZY462471 harboured an immune evasion cluster (IEC)-carrying βC-Φ, which is typically found in human clinical S. aureus rather than LA-MRSA isolates, suggesting that ZY4762471 obtained the IEC-carrying βC-Φs from human clinical S. aureus strains. Considering its high virulence potential, this strain should be monitored to prevent more widespread dissemination.

Clostridioides difficile is the most common pathogen causing antibiotic-associated diarrhea. Previous studies showed that diverse sources, aside from C. difficile infection (CDI) patients, played a major role in C. difficile hospital transmission. This study aimed to investigate relationships and transmission potential of C. difficile strains from different sources. A prospective study was conducted both in the intensive care unit (ICU) and six livestock farms in China in 2018–2019. Ninety-eight strains from CDI patients (10 isolates), asymptomatic hospitalized carriers (55), the ICU environment (12), animals (14), soil (4), and farmers (3) were collected. Sequence type (ST) 3/ribotype (RT) 001, ST35/RT046, and ST48/RT596 were dominant types, distributed widely in multiple sources. Core-genome single-nucleotide polymorphism (cgSNP) analysis showed that hospital and farm strains shared several common clonal groups (CGs, strains separated by ≤ 2 cgSNPs) (CG4/ST3/RT001, CG7/ST35/RT046, CG11/ST48/RT596). CDI patients, asymptomatic carriers, and the ICU environment strains also shared several common CGs. The number of virulence genes was not statistically different between strains from different sources. Multi-source strains in the same CG carried identical virulence gene sequences, including pathogenicity genes at the pathogenicity locus and adhesion-related genes at S-layer cassette. Resistance genes (ermB, tetM, etc.) were widespread in multiple sources, and multi-source strains in the same CG had similar resistance phenotypes and carried consistent transposons and plasmid types. The study indicated that interspecies and cross-regional transmission of C. difficile occurs between animals, the environment, and humans. Community-associated strains from both farms and asymptomatic hospitalized carriers were important reservoirs of CDI in hospitals.

Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable prognosis compared with other non-acute promyelocytic leukemia AML patients, only ~50% patients with this relatively favorable subtype can survive for 5 years and refractory/relapse is common in clinical practice. So it is necessary to find novel agents to treat this type of AML. In this study, the effects and the mechanisms of plumbagin and recombinant soluble tumor necrosis factor‑α-related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi‑1 cells were primarily investigated. Plumbagin and/or rsTRAIL could significantly inhibit the growth of Kasumi‑1 cells and induce apoptosis in vitro and in vivo. Plumbagin enhanced TRAIL-induced apoptosis of Kasumi‑1 cells in association with mitochondria damage, caspase activation, upregulation of death receptors (DRs) and decreased cFLIP expression. The effects of plumbagin on the expression of DR5, Bax and cFLIP could be partially abolished by the reactive oxygen species (ROS) scavenger NAC. Glutathione (GSH) depletion by plumbagin increased the production of ROS. In vivo, there was no obvious toxic pathologic change in the heart, liver and kidney tissues in any of the groups. Comparing with the control mice, a significantly increased number of apoptotic cells were observed in the combined treated mice by flow cytometry. Plumbagin also increased the expression of DR4 and DR5 in cells of xenograft tumors. Collectively, our results suggest that both plumbagin and rsTRAIL could be used as a single agent or synergistical agents to induce apoptosis of leukemic Kasumi‑1 cells in vitro and in vivo.