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ObjectivesThis study describes the detection and tracking of emergency neurosurgical cross-transmission infections with carbapenem-resistant Klebsiella oxytoca (CRKO).MethodsWe conducted an epidemiological investigation and a rapid screening of 66 surveillance samples using the chromogenic selective medium. Two CRKO isolates from infected patients and three from the preoperative shaving razors had similar resistance profiles identified by the clinical laboratory.ResultsThe whole genome sequencing (WGS) results identified all isolates as Klebsiella michiganensis (a species in the K. oxytoca complex) with sequence type 29 (ST29) and carrying resistance genes blaKPC-2 and blaOXY-5, as well as IncF plasmids. The pairwise average nucleotide identity values of 5 isolates ranged from 99.993% to 99.999%. Moreover, these isolates displayed a maximum genetic difference of 3 among 5,229 targets in the core genome multilocus sequence typing scheme, and the razors were confirmed as the contamination source. After the implementation of controls and standardized shaving procedures, no new CRKO infections occurred.ConclusionContaminated razors can be sources of neurosurgical site infections with CRKO, and standard shaving procedures need to be established. Chromogenic selective medium can help rapidly identify targeted pathogens, and WGS technologies are effective mean in tracking the transmission source in an epidemic or outbreak investigation. Our findings increase the understanding of microbial transmission in surgery to improve patient care quality.

In total, 49 clinical samples were analyzed using two typing schemes, Enhanced Centers for Disease Control and Prevention (ECDC) and multilocus sequence typing (MLST), to describe the molecular characteristics of circulating Treponema pallidum isolates in Xiamen between 2016 and 2017. In addition, genetic mutations potentially related to antibiotic resistance of T. pallidum were also analyzed. Forty five samples were fully typed by ECDC, and 14 different subtypes were detected. The most common subtype was 16d/f (24.4%), followed by 14d/f (20.0%). All forty nine samples were successfully typed by MLST, while only four allelic profiles were identified, including three SS14-like profiles and one Nichols-like profile. Among them, the major allelic profile was 1.1.8 (85.7%). Interestingly, the allelic profile 1.3.1 widespread in Europe and North America was not detected in this region. Additionally, A2058G mutation in 23S rRNA was found in all detectable samples (38/38), and no mutation in 16S rRNA was observed (36/36). Four non-synonymous single-nucleotide polymorphisms in penicillin-binding protein genes were found in the 35 samples eligible for Sanger sequencing. Among them, the variant in tp0500 (P564I) can only be found in the SS14-like isolates. Homoplastic changes in tp0760 (I415F/I415M) and tp0705 (A506V/A506T) were found. Moreover, the variant tp0705 A506V and the variant tp0705 A506T separately appeared in the SS14-like isolates and Nichols-like isolates, respectively. This study showed that the genotypes of T. pallidum isolates in Xiamen between 2016 and 2017 were different from those in other geographic areas. The resistance-related variants of T. pallidum isolates identified in this study could provide awareness for clinicians in the treatment of syphilis.

Monocytes are widely involved in the body’s defense response, and abnormally regulated monocyte subsets are closely related to the pathogenesis of various diseases. It is unclear whether Treponema pallidum (Tp) dysregulates monocyte subsets and impacts the functions of monocytes. This study aims to analyze the distribution of monocyte subsets in syphilis patients and the effect of Tp on monocyte functions to explore the pathogenesis of syphilis. Flow cytometry was employed to detect monocyte subsets. With or without pre-treatment with rapamycin, THP-1 cell migration stimulated by Tp was investigated by a Transwell migration assay, and THP-1 cell phagocytosis was studied using fluorescent microspheres. IL-1β and TNF-α expression was quantified by PCR and flow cytometry, while LC3 and mTOR were investigated in Tp-exposed THP-1 cells using western blotting. Tp infection led to an increase in the proportion of CD14++CD16+ monocytes and a decrease in the proportion of CD14++CD16- monocytes. In addition, Tp promoted monocyte (THP-1) CD14 and CD16 expression in vitro, induced the expression of IL-1β and TNF-α in a dose-dependent manner and promoted the migration and autophagy of monocytes. Furthermore, mTOR phosphorylation on monocytes was stimulated by Tp, and the levels peaked at 30 min. Pre-treatment with rapamycin (mTOR inhibitor) attenuated the expression of IL-1β and migration in Tp-exposed THP-1 cells. Tp abnormally regulates monocyte subsets and promotes migration, autophagy, and the expression of IL-1β and TNF-α in THP-1 cells. Meanwhile, the mTOR affected the expression of IL-1β and migration in Tp-exposed THP-1 cells. This study is important as it sheds light on the mechanism by which monocytes interact with Tp during infection.

The pathological features of syphilis, a disease caused by Treponema pallidum (T. pallidum), are characterized by vascular involvement with endarteritis and periarteritis. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. In the present study, we demonstrated that stimulation of HDVSMCs with T. pallidum resulted in the upregulated gene transcription and protein expression of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) in a dose- and time-dependent manner. Moreover, the migration and adhesion of THP-1 cells to HDVSMCs were significantly suppressed by anti-MCP-1 and anti-ICAM-1 neutralizing antibodies, respectively. Further studies revealed that T. pallidum activated the NF-κB signaling pathway in HDVSMCs. Inhibition of NF-κB suppressed T. pallidum-induced IL-6, MCP-1, and ICAM-1 expression. In addition, the migration and adhesion of THP-1 cells to T. pallidum-treated HDVSMCs were significantly decreased by pretreatment with an NF-κB inhibitor. These findings demonstrate that T. pallidum induces the production of IL-6, MCP-1, and ICAM-1 in HDVSMCs and promotes the adherence and migration of THP-1 cells to HDVSMCs through the NF-κB signaling pathway, which may provide new insight into the pathogenesis of T. pallidum infection.

Recent studies have shown that several long noncoding RNAs (lncRNAs) are involved in regulating the immune response to cope with pathogenic invasion. To date, the roles of lncRNAs in the CD4+ T cell response to Treponema pallidum (T. pallidum) infection in neurosyphilis patients remain unknown. The mRNA and lncRNA expression profiles of CD4+ T cells that were isolated from neurosyphilis patients and healthy controls were analyzed by microarray. A total of 2258 lncRNAs and 1728 mRNAs were identified as over-expressed or under-expressed, respectively (fold change > 1.5) in the CD4+ T cells of neurosyphilis patients compared to the healthy controls. The lncRNA-mRNA co-expression network showed that 59 lncRNAs showed significant differences along with significantly different mRNAs. Among the 59 gene pairs, the LOC79999 mRNA was positively correlated with the RP11-160E2.16, RP11-160E2.11, and RP11-160E2.19 lncRNAs, and the NKX1-1 mRNA was positively correlated with the RP11-1398P2.1, RP11-160E2.19, and XLOC_003422 lncRNAs. The following five mRNAs were correlated with two differential lncRNAs: DUSP16, AP000349.1, FAM115C, TIMM8A, and SMCHD1. Gene Ontology (GO) analysis revealed that the differentially expressed coding genes were mainly involved in biological processes and the top 4 terms that associated with above-mentioned differentially expressed coding genes were as follows: defense response to fungus, defense response to bacterium, killing of cells of other organism and disruption of cells of another organism. A subsequent pathway analysis was also conducted, and several pathways, including the T cell receptor, MAPK, and TGF-beta signaling pathways, were associated with the differentially expressed mRNAs. This study reveals the differential expression profiles of lncRNAs in the CD4+ T cell response to the T. pallidum infection in neurosyphilis patients. LncRNAs are involved in key biological processes that comprise the CD4+ T cell response to the T. pallidum infection.