In a previous study, differential proteomic analysis was used to identify membrane proteins of the human enteropathogen
, whose levels are influenced by OmpR, the transcriptional regulator in the ...two-component EnvZ/OmpR system. Interestingly, this analysis demonstrated that at 37 °C, OmpR negatively affects the level of over a dozen Ysc-Yop proteins, which constitute a type III secretion system (T3SS) that is essential for the pathogenicity of
. Here, we focused our analysis on the role of OmpR in the expression and secretion of Yops (translocators and effectors). Western blotting with anti-Yops antiserum and specific anti-YopD, -YopE and -YopH antibodies, confirmed that the production of Yops is down-regulated by OmpR with the greatest negative effect on YopD. The RT-qPCR analysis demonstrated that, while OmpR had a negligible effect on the activity of regulatory genes
and
, it highly repressed the expression of
. OmpR was found to bind to the promoter of the
operon, suggesting a direct regulatory effect. In addition, we demonstrated that the negative regulatory influence of OmpR on the Ysc-Yop T3SS correlated with its positive role in the expression of
, the master regulator of the flagellar-associated T3SS.
Wilson disease (WD) is an inherited genetic disorder that is caused by copper metabolism disturbances with main hepatic, neurological, and psychiatric presentation. Deposits of copper accumulate in ...different organs and may cause a broad range of clinical manifestations. Patients with WD may present with ophthalmological symptoms, or renal, cardiac and osteoarticular involvement. The most common ophthalmological sign as a result of copper accumulation is the Kayser-Fleischer corneal ring, whereas sunflower cataracts are observed rarely. Retinal degeneration, present in WD patients, may serve as a marker of neurodegeneration. Osteoarticular involvement is quite common and includes osteopenia, osteoporosis and arthropathy, which may lead to bone fractures and joint problems mainly affecting knees and wrists. Renal disturbances include tubular dysfunction and renal calculi. A recent cardiac study has shown a higher risk of atrial fibrillation and heart failure in WD patients than in non-WD patients. Autonomic system dysfunction is also observed, but involvement is subclinical in most cases. Another manifestation of WD concerns endocrine system disturbances, which can lead to recurrent abortions, infertility, growth disruption, and parathyroid failure. However, it is possible to become pregnant for females with mild WD symptoms and for those who are compliant with therapy. Hematologic disturbances are frequent and may include acute hemolytic anemia, leucopenia, anemia and low platelet count. Other observed symptoms include lipomas and characteristic of WD skin changes like hyperpigmentation of the legs, xerosis or azure lunulae of the nails. In this paper, we present some of the less common, but nevertheless, important manifestations of WD.
In this study, we found that the loss of OmpR, the response regulator of the two-component EnvZ/OmpR system, increases the cellular level of Fur, the master regulator of iron homeostasis in
. ...Furthermore, we demonstrated that transcription of the
gene from the YeP
promoter is subject to negative OmpR-dependent regulation. Four putative OmpR-binding sites (OBSs) were indicated by in silico analysis of the
promoter region, and their removal affected OmpR-dependent
expression. Moreover, OmpR binds specifically to the predicted OBSs which exhibit a distinct hierarchy of binding affinity. Finally, the data demonstrate that OmpR, by direct binding to the promoters of the
,
and
genes, involved in the iron transport and being under Fur repressor activity, modulates their expression. It seems that the negative effect of OmpR on
and
transcription is sufficient to counteract the indirect, positive effect of OmpR resulting from decreasing the Fur repressor level. The expression of
was positively regulated by OmpR and this mode of action seems to be direct and indirect. Together, the expression of
,
and
in
has been proposed to be under a complex mode of regulation involving OmpR and Fur regulators.
Iron is both essential for and potentially toxic to bacteria, so the precise maintenance of iron homeostasis is necessary for their survival. Our previous study indicated that in the human ...enteropathogen
, the regulator OmpR directly controls the transcription of the
,
and
genes, encoding the ferric uptake repressor and two transporters of ferric siderophores, respectively. This study was undertaken to determine the significance of the RNA chaperone Hfq and the small RNAs OmrA and RyhB1 in the post-transcriptional control of the expression of these OmpR targets. We show that Hfq silences
,
and
expression post-transcriptionally and negatively affects the production of FLAG-tagged Fur, FecA and FepA proteins. In addition, we found that the
gene is under the negative control of the sRNA RyhB1, while
and
are negatively regulated by the sRNA OmrA. Finally, our data revealed that the role of OmrA results from a complex interplay of transcriptional and post-transcriptional effects in the feedback circuit between the regulator OmpR and the sRNA OmrA. Thus, the expression of
,
and
is subject to complex transcriptional and post-transcriptional regulation in order to maintain iron homeostasis in
.
Despite rapid growth in the significance of dermoscopy in dermatological oncology, relatively little is yet known about the dermoscopic patterns of eyelid margin tumors. The aim of the study was to ...analyze the dermoscopic features of eyelid margin tumors. This was a retrospective, single‐center, consecutive study which included clinical and dermoscopic analysis of eyelid margin tumors diagnosed at the Department of Dermatology, Venereology and Allergology at the Medical University of Gdańsk from 1 June 2016 to 31 December 2020. Dermoscopic features significantly more prevalent in malignant non‐melanocytic lesions compared to benign ones were alteration in eyelash growth, structureless pink areas, starry milia‐like cysts, and perpendicular vessels. In contrast, there were no dermoscopic features that occurred significantly more frequently in malignant melanocytic lesions when compared to benign ones. Basal cell carcinoma, in comparison to hidrocystoma, more commonly presented with ulceration and structureless pink areas. The main features differentiating basal cell carcinoma from dermal nevus were the presence of ulceration, alteration in eyelash growth, structureless pink and structureless white areas, and perpendicular vessels within the tumor with each of these features observed more commonly in basal cell carcinoma. Blue nevus, hemangioma, or pigmented hidrocystoma presenting exclusively with blue structureless areas may be difficult to differentiate based on dermoscopy. The study offers additional dermoscopic clues in the assessment of eyelid margin tumors. Some observations reported previously to be typical of basal cell carcinoma (e.g., linear vessels arranged perpendicularly to the eyelid margin) were documented also within the normal eyelid margin accompanying other cases, and according to our study, cannot be useful as a pathognomonic feature. In contrast, it seems that yellow structures (half‐moon sign, starry milia‐like cysts) may be important dermoscopic features, though further studies are needed to confirm our observations.
exhibits a dual lifestyle, existing as both a saprophyte and a pathogen colonizing different niches within a host organism. OmpR has been recognized as a regulator that controls the expression of ...genes involved in many different cellular processes and the virulence of pathogenic bacteria. Here, we have examined the influence of OmpR and varying temperature (26°C vs. 37°C) on the cytoplasmic proteome of
.
Ye9N (bio-serotype 2/O:9, low pathogenicity). Differential label-free quantitative proteomic analysis indicated that OmpR affects the cellular abundance of a number of proteins including subunits of urease, an enzyme that plays a significant role in acid tolerance and the pathogenicity of
. The impact of OmpR on the expression of urease under different growth conditions was studied in more detail by comparing urease activity and the transcription of
genes in
strains Ye9N and Ye8N (highly pathogenic bio-serotype 1B/O:8). Urease expression was higher in strain Ye9N than in Ye8N and in cells grown at 26°C compared to 37°C. However, low pH, high osmolarity and the presence of urea did not have a clear effect on urease expression in either strain. Further analysis showed that OmpR participates in the positive regulation of three transcriptional units encoding the multi-subunit urease (
,
, and
) in strain Ye9N, but this was not the case in strain Ye8N. Binding of OmpR to the
and
promoter regions was confirmed using an electrophoretic mobility shift assay, suggesting that this factor plays a direct role in regulating the transcription of these operons. In addition, we determined that OmpR modulates the expression of a
-like gene encoding a putative regulator of the
gene cluster, but in the opposite manner, i.e., positively in Ye9N and negatively in Ye8N. These findings provide some novel insights into the function of OmpR in adaptation strategies of
.
Bacteria have evolved numerous regulatory pathways to survive in changing environments. The SOS response is an inducible DNA damage repair system that plays an indispensable role in bacterial ...adaptation and pathogenesis. Here we report a discovery of the previously uncharacterized protein Lmo0946 as an SOS response interfering factor (Sif) in the human pathogen
Functional genetic studies demonstrated that
is indispensable for normal growth of
in stress-free as well as multi-stress conditions, and
contributes to susceptibility to β-lactam antibiotics, biofilm formation and virulence. Absence of Sif promoted the SOS response and elevated expression of mobilome genes accompanied by mobilization of the A118 prophage and ICELm-1 mobile genetic elements (MGEs). These changes were found to be associated with decreased expression of general stress response genes from the σB regulon as well as virulence genes, including the PrfA regulon. Together, this study uncovers an unexpected role of a previously uncharacterized factor, Sif, as an inhibitor of the SOS response in
.
Streszczenie Małe, regulatorowe RNA (sRNA) wraz z dwuskładnikowymi systemami transdukcji sygnału (TCS) wchodzą w skład rozbudowanych sieci kontroli ekspresji genów bakteryjnych. Oddziałując ze sobą ...wzajemnie, zapewniają niezwykle szybką, jak również precyzyjną odpowiedź bakterii na zmieniające się warunki bytowania. Kontrolując wiele procesów wpływają na stan fizjologiczny komórki, skład proteomu osłon komórkowych czy zdolność do wzrostu w postaci biofilmu. Niezwykle często sRNA stanowią brakujące ogniwa, w odpowiedzi na złożone bodźce środowiskowe, pomiędzy dwuskładnikowymi systemami transdukcji sygnału, a genami docelowymi czy innymi systemami regulatorowymi. Współdziałanie TCS-sRNA wydaje się globalną cechą regulacyjną u wielu organizmów prokariotycznych. Zdobywanie wiedzy na temat tych mechanizmów kontroli toruje drogę do opracowania nowych strategii walki z drobnoustrojami patogennymi.
We show that
strain Ye9 (bio-serotype 2/O:9) utilizes heme-containing molecules as an iron source. The Ye9 genome contains two multigenic clusters,
-1 and
-2, encoding putative heme receptors HemR1 ...and HemR2, that share 62% amino acid identity. Expression of these proteins in an
mutant defective in heme biosynthesis allowed this strain to use hemin and hemoglobin as a source of porphyrin. The
-1 and
-2 clusters are organized as operons, expressed from the p
and weaker p
promoters, respectively. Expression of both operons is negatively regulated by iron and the iron-responsive transcriptional repressor Fur. In addition, OmpR, the response regulator of two component system (TCSs) EnvZ/OmpR, represses transcription of both operons through interaction with binding sequences overlapping the -35 region of their promoters. Western blot analysis of the level of HemR1 in
, and
mutants, showed an additive effect of these mutations, indicating that OmpR may regulate HemR expression independently of Fur. However, the effect of OmpR on the activity of the p
promoter and on HemR1 production was observed in both iron-depleted and iron-replete conditions, i.e., when Fur represses the iron-regulated promoter. In addition, a hairpin RNA thermometer, composed of four uracil residues (FourU) that pair with the ribosome-binding site in the 5'-untranslated region (5'-UTR) of
was predicted by
analysis. However, thermoregulated expression of HemR1 could not be demonstrated. Taken together, these data suggest that Fur and OmpR control iron/heme acquisition via a complex mechanism based on negative regulation of
and
at the transcriptional level. This interplay could fine-tune the level of heme receptor proteins to allow
to fulfill its iron/heme requirements without over-accumulation, which might be important for pathogenic growth within human hosts.
There is growing evidence of the potential uses of dermoscopy in diagnostics of demodicosis. No previous studies have analyzed dermoscopic features in patients with ocular demodicosis.
To evaluate ...the potential usefulness of videodermoscopy in diagnostics of ocular demodicosis.
It was a single-center prospective observational study in which results of videodermoscopic examination of the eyelids were compared to the results of classic microscopic examination in patients with suspected ocular demodicosis and healthy volunteers.
Study group included 16 women and 15 men. In fifteen (48.4%) patients, microbiological examination of epilated eyelashes was positive. The results of forms filled by the patients concerning known subjective clinical symptoms of ocular demodicosis revealed no significant differences between the group with positive and negative results of microscopic examination. The presence of Demodex tails and madarosis observed during dermoscopic assessment correlated positively with positive results of microscopic examination. At least one Demodex tail was found in 86.7% (13/15) cases with positive results of microscopic examination. In the two remaining cases microscopic evaluation showed the presence of Demodex brevis. In 37.5% (6/16) of patients with negative results of microscopic examination, videodermoscopy showed the presence of Demodex tails.
Videodermoscopy may facilitate the diagnostics of ocular demodicosis. Patients reporting clinical symptoms suggesting ocular demodicosis but negative results of videodermoscopic examination should be referred to classical microscopic examination to exclude the presence of Demodex brevis. In patients with negative microscopic examination results and symptoms suggesting ocular demodicosis, dermoscopy-guided microscopic re-evaluation could be considered.
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