Search

Abstract Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45+lineage–CD90.2+NK1.1–NKp46–ST2–KLRG1+IL-17RB+ memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence.

Abstract Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins is commonly associated with a variety of stress responses and cellular processes in eukaryotes, but its potential roles in bacteria are unclear. Here, we show that protein HmwC acts as an O-GlcNAc transferase (OGT) responsible for O-GlcNAcylation of multiple proteins in Yersinia pestis, a flea-borne pathogen responsible for plague. We identify 64 O-GlcNAcylated proteins (comprising 65 sites) with differential abundance under conditions mimicking the mammalian host (Mh) and flea vector (Fv) environments. Deletion of hmwC, encoding a putative OGT, structurally distinct from any existing member of the GT41 family, results in reduced O-GlcNAcylation, reduced growth, and alterations in virulence properties and survival under stress. Purified HmwC can modify target proteins in vitro using UDP-GlcNAc as sugar donor. One of the target proteins, OsdY, promotes Y. pestis survival under oxidative stress conditions. Thus, our results support that regulation of antioxidative responses through O-GlcNAcylation may be a conserved process shared by prokaryotes and eukaryotes.

Abstract Plague, caused by Yersinia pestis, is a zoonotic disease that can reemerge and cause outbreaks following decades of latency in natural plague foci. However, the genetic diversity and spread pattern of Y. pestis during these epidemic-silent cycles remain unclear. In this study, we analyze 356 Y. pestis genomes isolated between 1952 and 2016 in the Yunnan Rattus tanezumi plague focus, China, covering two epidemic-silent cycles. Through high-resolution genomic epidemiological analysis, we find that 96% of Y. pestis genomes belong to phylogroup 1.ORI2 and are subdivided into two sister clades (Sublineage1 and Sublineage2) characterized by different temporal-spatial distributions and genetic diversity. Most of the Sublineage1 strains are isolated from the first epidemic-silent cycle, while Sublineage2 strains are predominantly from the second cycle and revealing a west to east spread. The two sister clades evolved in parallel from a common ancestor and independently lead to two separate epidemics, confirming that the pathogen responsible for the second epidemic following the silent interval is not a descendant of the causative strain of the first epidemic. Our results provide a mechanism for defining epidemic-silent cycles in natural plague foci, which is valuable in the prevention and control of future plague outbreaks.

Guanylate-binding proteins (GBPs) recognize pathogen containing vacuoles, leading to lysis of this intracellular niche and induction of inflammasomes. Here, Cao et al. show that Y. pestis, the causative agent of plague, secret two functionally redundant E3 ligase, YspE1 and YspE2, into the host’s cytosol to ubiquitinate multiple GBPs for proteasomal degradation to subvert host immune defense. This capability appears to be newly acquired by Y. pestis during evolution, since its closely related progenitor Y. pseudotuberculosis is unable to do so.

Abstract Ureteral stent removal by an extraction string is advantageous. However, the increased risk of complications attributed to the continuous exposure of the string outside the urethra must be managed. This paper introduces a method to decrease the exposure time, and conducts a retrospective study to verify its efficiency and safety. A total of 231 male patients undergoing routine ureteroscopy (URS) were included, and all of them accepted indwelling ureteral stents with strings. Among them, 123 patients (Normal-S group) underwent the normal method to determine the length of string (Lstring), which was shortened to 4 cm (cm) past the urethral meatus; 108 patients (Novel-S group) underwent the novel method (Lstring = Lurethra + 2 cm), the length of urethra (Lurethra) was measured during ureteroscopy by ureteroscope body. The demographic characteristics, stent indwelling and removal-related variables, complications, and medical costs in each group were recorded. There was no significant difference in demographic characteristics, the rate of UTI, the operative duration of URS, or the VAS pain scores for stent removal between the 2 groups. For the Novel-S group, the stent dwelling time was longer, the self-rated discomfort and symptom, the stent dislodgement rate, the numbers of clinic or emergency visits and the overall medical cost post operation was lower in comparison with the Normal-S group, while the rate of removal of stents by hand was lower, the time for removing ureteral stents was longer. This novel method improved stenting comfort, avoided ureteral stent dislodgement, decreased complications, and lowered medical costs, it was safe and reliable and merits widespread application.

Yersinia pestis, the causative agent of plague, can change its biofilm production to influence the dynamics of flea-borne transmission. Here, the authors sequence Y. pestis isolates sampled over 40 years in China and show evidence for climate-associated selection on rpoZ to increase biofilm production.

Abstract Although clinical antibiotic-resistant bacteria have attracted tremendous attention in the microbiology community, the resistant bacteria that persist in natural environments have been overlooked for a longtime. We previously proposed a new species Paramesorhizobium desertii, isolated from the soil of the Taklimakan Desert in China that is highly resistant to most β-lactam antibiotics. To identify potential β-lactamase(s) in this bacteria, we first confirmed the carbapenemase activity in the freeze–thawed supernatant of a P. desertii A-3-ET culture using the modified Hodge assay. We then identified a novel chromosome-encoded carbapenemase (PAD-1) in strain A-3-ET, using a shotgun proteomic analysis of the supernatant and genomic information. The bioinformatics analysis indicated that PAD-1 is a class A carbapenemase. Subsequent enzyme kinetic assays with purified PAD-1 confirmed its carbapenemase activity, which is similar to that of clinically significant class A carbapenemases, including BKC-1 and KPC-2. Because the location in which A-3-ET was isolated is not affected by human activity, PAD-1 is unlikely to be associated with the selection pressures exerted by modern antibiotics. This study confirmed the diversity of antibiotic-resistant determinants in the environmental resistome.

Abstract This study aimed to genetically characterize two fully-sequenced novel IncFII-type multidrug resistant (MDR) plasmids, p0716-KPC and p12181-KPC, recovered from two different clinical Klebsiella pneumoniae isolates. p0716-KPC and p12181-KPC had a very similar genomic content. The backbones of p0716-KPC/p12181-KPC contained two different replicons (belonging to a novel IncFII subtype and the Rep_3 family), the IncFIIK and IncFIIY maintenance regions, and conjugal transfer gene sets from IncFIIK-type plasmids and unknown origins. p0716-KPC and p12181-KPC carried similar three accessory resistance regions, namely ΔTn6209, a MDR region, and the bla KPC-2 region. Resistance genes bla KPC-2, mph(A), strAB, aacC2, qacEΔ1, sul1, sul2, and dfrA25, which are associated with transposons, integrons, and insertion sequence-based mobile units, were located in these accessory regions. p0716-KPC carried two additional resistance genes: aphA1a and bla TEM-1. Together, our analyses showed that p0716-KPC and p12181-KPC belong to a novel IncFII subtype and display a complex chimeric nature, and that the carbapenem resistance gene bla KPC-2 coexists with a lot of additional resistance genes on these two plasmids.