Our data suggest that lncRNAs in exosomes isolated from cervicovaginal lavage are differentially expressed in cervical cancer patients and cancer-free volunteers. Exosomal lncRNAs may have great potential to be used for the early detection and diagnosis of cervical cancer, and serve as convenient and noninvasive biomarkers.

K1/K2 hvKP strains acquire carbapenem-resistance plasmids, known as CR-hvKp, and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains obtain virulence plasmids, recognized as hv-CRKP. The two different evolution patterns of hypervirulent combined carbapenem-resistant Klebsiella pneumoniae may lead to their different prevalence in hospitals. Our study aimed to investigate the prevalence of hv-CRKP and CR-hvKp strains and to analyze factors influencing their evolution and prevalence. We collected 890 K. pneumoniae genomes from GenBank and 530 clinical K. pneumoniae isolates from nine hospitals. Our study found that hv-CRKP strains were more prevalent than CR-hvKp strains and both were dominated by bla KPC-2 gene. The bla KPC-2 -carrying plasmids could mobilize non-conjugative virulence plasmids from hvKp strains to CRKP strains. The conserved oriT of virulence plasmids and the widespread of conjugative helper plasmids were potential factors for the mobilization of non-conjugative virulence plasmids. HvKp strains with KPC plasmid could hardly simultaneously exhibit hypervirulence and carbapenem resistance as CRKP strains with virulence plasmid, and we found that rfaH mutation reduced capsular synthesis and increased carbapenem resistance of the CR-hvKp strain. In summary, this study revealed that hv-CRKP strains were more suitable for survival in hospital settings than CR-hvKp strains and the widespread conjugative KPC-producing plasmids contributed to the emergence and prevalence of hv-CRKP strains.

IntroductionA high incidence of myocardial infarction among patients with gout has been suggested by several observational studies. We performed a meta-analysis to evaluate the association between gout and the risk of myocardial infarction.Materials and MethodsThe PubMed and Embase databases were searched from inception to October 2014 for cohort studies that evaluating the association between gout and the risk of myocardial infarction. Summary estimates were derived using a random-effects model and reported as relative risks (RRs) with 95% confidence intervals (CIs).ResultsFive studies involving 8,656,413 participants with a total of 1000 MI events were included. Overall, gout was associated with an increased risk of myocardial infarction (RR 1.45; 95% CI, 1.19–1.75; p<0.001), and the association referred to non-fatal myocardial infarction (RR 1.29; 95% CI, 1.19–1.39; p <0.001) but not fatal myocardial infarction (RR 1.11; 95% CI, 0.96–1.28; p = 0.174). The increased risk was observed in both women (RR 1.62; 95% CI, 1.18–2.21; p = 0.003) and men (RR 1.45; 95% CI, 1.21–1.74; p <0.001). Stratified analysis revealed a gradual increase in myocardial infarction risk with a younger age of gout onset (age 20–44 years old (RR 2.82; 95% CI, 1.38–5.79; p = 0.05); 45–69 years old (RR 1.85; 95% CI, 1.22–2.82; p = 0.04); ≥70 years old (RR 1.52; 95% CI, 1.22–1.88; p <0.001)).ConclusionThis meta-analysis suggests that patients with gout have an increased risk of myocardial infarction.

Virulence plasmids of hypervirulent Klebsiella pneumoniae (hvKp) have the potential to transfer to drug-resistant strains or integrate with other plasmids, facilitating the genome evolution of threatening pathogens. We conducted an in-depth analysis of the publicly available 156 complete genome sequences of hvKp together with a multi-region clinical cohort of 171 hvKp strains from China to provide evidence for the virulence plasmid evolution. Virulence plasmids were frequently detected in the ST23 and ST11 K. pneumoniae strains. Multidrug-resistant hvKp (MDR-hvKp) occupied a large proportion of hvKp, and the coexistence of virulence and resistance plasmids may be the major cause. Virulence plasmids commonly possessed multiple replicons, of which IncFIB K was the most prevalent (84.6%). We identified 49 IncFIB K alleles among 583 IncFIB K plasmids, and they could be divided into Clades I, II, and III. We further observed that conjugative and non-conjugative virulence plasmids could be distinguished by IncFIB K genetic diversity, and IncFIB K subtyping could also indirectly indicate a chimeric preference of conjugative virulence plasmids. On this basis, we developed an open-access web tool called KpVR for IncFIB K subtyping. In conclusion, the genetic diversity of IncFIB K virulence plasmids could be used for tracking the evolution of virulence plasmids, and further preventing the emergence of MDR-hvKp strains.

ObjectiveTo investigate the overall distributions of key virulence genes in Klebsiella pneumoniae, especially the hypervirulent blaKPC-positive K. pneumoniae (Hv-blaKPC(+)-KP).MethodsA total of 521 complete genomes of K. pneumoniae from GenBank were collected and analyzed. Multilocus sequence typing, molecular serotyping, antibiotic-resistance, virulence genes and plasmid replicon typing were investigated.ResultsPositive rates of virulence genes highly varied, ranging from 2.9 (c-rmpA/A2) to 99.6% (entB). Totally 207 strains presented positive fimH, mrkD, entB and wzi and 190 showed positive fimH, mrkD, entB, irp2 and wzi, which were the two primary modes. A total of 94, 165 and 29 strains were denoted as hypervirulent K. pneumoniae (HvKP), blaKPC(+)-KP and Hv-blaKPC(+)-KP. ST11 accounted for 17 among the 29 Hv-blaKPC(+)-KP strains; Genes iucA, p-rmpA2 and p-rmpA were positive in 28, 26 and 18 Hv-blaKPC(+)-KP strains respectively. Among the 29 Hv-blaKPC(+)-KP strains exhibiting four super clusters from GenBank, IncHI1B plasmids carrying virulence genes and IncFII ones with blaKPC were responsible for both 23 strains respectively.ConclusionsPositive rates of virulence genes vary remarkably in K. pneumoniae. Genes iucA, p-rmpA2 and p-rmpA were primary ones inducing Hv-blaKPC(+)-KP. IncHI1B plasmids carrying virulence genes and IncFII ones with blaKPC constitute the primary combination responsible for Hv-blaKPC(+)-KP. The making of Hv-blaKPC(+)-KP is mostly via blaKPC(+)-KP acquiring another plasmid harboring virulence genes.

To demonstrate the detailed genetic characteristics of a blaNDM–1-carrying multidrug-resistant Aeromonas caviae strain, the complete genome of the A. caviae strain K433 was sequenced by Illumina HiSeq and Oxford nanopore platforms, and mobile genetic elements associated with antibiotic resistance genes were analyzed by a series of bioinformatics methods. A. caviae K433 which was determined to produce class B carbapenemase, was resistant to most antibiotics tested except amikacin. The genome of K433 consisted of a chromosome cK433 (6,482-kb length) and two plasmids: pK433-qnrS (7.212-kb length) and pK433-NDM (200.855-kb length), the last being the first investigated blaNDM-carrying plasmid from Aeromonas spp. By comparison of the backbone and MDR regions from the plasmids studied, they involved a highly homologous sequence structure. This study provides in-depth genetic insights into the plasmids integrated with blaNDM-carrying genetic elements from Aeromonas spp.

Klebsiella pneumoniae is a notorious bacterium in clinical practice. Virulence, carbapenem‐resistance and their convergence among K. pneumoniae are extensively discussed in this article. Hypervirulent K. pneumoniae (HvKP) has spread from the Asian Pacific Rim to the world, inducing various invasive infections, such as pyogenic liver abscess, endophthalmitis, and meningitis. Furthermore, HvKP has acquired more and more drug resistance. Among multidrug‐resistant HvKP, hypervirulent carbapenem‐resistant K. pneumoniae (Hv‐CRKP), and carbapenem‐resistant hypervirulent K. pneumoniae (CR‐HvKP) are both devastating for their extreme drug resistance and virulence. The hypervirulence of HvKP is primarily attributed to hypercapsule, macromolecular exopolysaccharides, or excessive siderophores, although it has many other factors, for example, lipopolysaccharides, fimbriae, and porins. In contrast with classical determination of HvKP, that is, animal lethality test, molecular determination could be an optional and practical method after improvement. HvKP, including Hv‐CRKP and CR‐HvKP, has been progressing. R‐M and CRISPR‐Cas systems may play pivotal roles in such evolutions. Hv‐CRKP and CR‐HvKP, in particular the former, should be of severe concern due to their being more and more prevalent.

BackgroundStreptococcus pneumoniae (SP) is the major cause of childhood mortality worldwide, we need to understand virulence genes of SP so can better target the treatment.We investigated the expression of virulence genes PsaA and CpsA in different strains of SP interacting with monocyte cell line (THP-1) or pneumocyte cell line (A549) and the possible mechanism of SP invasion of the blood system.MethodsA total of 23 strains of SP were collected from hospitalized patients (blood-derived and sputum-derived) in the Second Affiliated Hospital of Wenzhou Medical College. The strains and ATCC 49619 were cultured, and RNAs were extracted. THP-1 and A549 cells were stimulated by different SP and ATCC 49619 for 4 h and 8 h, respectively. Quantitative real-time PCR was used to analyze the mRNA expression of PsaA and CpsA. The data were analyzed by SPSS 17.0.ResultsThe mRNA level of PsaA and CpsA were all significantly increased in clinical SP strains when compared to ATCC49619 after tedTHP-1 and A549 cells were stimulated. Clinical SPs showed higher virulence compared with ATCC49619.ConclusionsThe expression of CpsA is the basis of the pathogenicity of SP. The expression of virulence gene PsaA may be helpful to the invasion of SP to the blood system.