Hypervirulent variants of Klebsiella pneumoniae (hvKp) that cause invasive community-acquired pyogenic liver abscess (PLA) have emerged globally. Little is known about the virulence determinants associated with hvKp, except for the virulence genes rmpA/A2 and siderophores (iroBCD/iucABCD) carried by the pK2044-like large virulence plasmid. Here, we collected most recent clinical isolates of hvKp from PLA samples in China, and performed clinical, molecular, and genomic sequencing analyses. We found that 90.9% (40/44) of the pathogens causing PLA were K. pneumoniae. Among the 40 LA-Kp, K1 (62.5%), and K2 (17.5%) were the dominant serotypes, and ST23 (47.5%) was the major sequence type. S1-PFGE analyses demonstrated that although 77.5% (31/40) of the LA-Kp isolates harbored a single large virulence plasmid varied in size, 5 (12.5%) isolates had no plasmid and 4 (10%) had two or three plasmids. Whole genome sequencing and comparative analysis of 3 LA-Kp and 3 non-LA-Kp identified 133 genes present only in LA-Kp. Further, large scale screening of the 133 genes in 45 LA-Kp and 103 non-LA-Kp genome sequences from public databases identified 30 genes that were highly associated with LA-Kp, including iroBCD, iucABCD and rmpA/A2 and 21 new genes. Then, these 21 new genes were analyzed in 40 LA-Kp and 86 non-LA-Kp clinical isolates collected in this study by PCR, showing that new genes were present 80–100% among LA-Kp isolates while 2–11% in K. pneumoniae isolates from sputum and urine. Several of the 21 genes have been proposed as virulence factors in other bacteria, such as the gene encoding SAM-dependent methyltransferase and pagO which protects bacteria from phagocytosis. Taken together, these genes are likely new virulence factors contributing to the hypervirulence phenotype of hvKp, and may deepen our understanding of virulence mechanism of hvKp.

BackgroundThe occurrence of non-contiguous, multiple, and remote involvement tuberculous spondylitis is rare. The clinical presentation in patients with multifocal musculoskeletal tuberculosis may closely mimic that in patients with multiple bone metastases, which makes the accurate clinical diagnosis challenging. Herein, we report a multifocal musculoskeletal tuberculosis case that was misdiagnosed for 8 months as multiple bone metastases.Case presentationA 63-year-old male farmer of Chinese Han ethnicity presented to us with pain in left side of the neck, right side of the chest and the back for 10 months without typical tuberculosis symptoms. His past medical history, the CT and fluoroscopy-guided biopsy were negative for tuberculosis. Interferon gamma by T-SPOT was also negative. Radiological findings including CT, MRI and PET-CT suggested that the patient had multiple metastases. Accordingly, the patient was misdiagnosed as having musculoskeletal tumors until a swelling under the right nipple ulcerated. The smear test for acid-fast bacilli and the PCR test for TB-DNA of the pus from the swollen area were both positive, leading to the final correct diagnosis of musculoskeletal tuberculosis.ConclusionThe proper diagnosis of musculoskeletal tuberculosis is clinically challenging due to Mycobacterium tuberculosis variants involved and atypical presentations, especially when the lesions are multiple. Our findings indicate that multiple tuberculous spondylitis must be considered in the differential diagnosis of multiple musculoskeletal lesions.

Objectives. This study investigated the functional mechanism of transmembrane protein 100 (TMEM100) as a tumor inhibitor gene in CRC cells and offered a reference for the treatment of CRC. Methods. The mRNA expression data of CRC were acquired from the TCGA database to mine differentially expressed mRNAs. The role of TMEM100 in the progression of CRC cells was evaluated by MTT, colony formation, scratch healing, and Transwell assays. The influence of TMEM100 on the TGF-β signaling pathway was detected by western blot. Results. TMEM100 was markedly lowly expressed in CRC. CRC cell growth was significantly suppressed by overexpressing TMEM100 but noticeably facilitated by silencing TMEM100. Overexpression of TMEM100 inhibited the activation of the TGF-β signaling pathway, thus inhibiting malignant progression of CRC. Conclusion. TMEM100 is lowly expressed in CRC, which can suppress CRC cell growth by regulating the TGF-β signaling pathway.