Role of Glucose-6-Phosphate in Metabolic Adaptation of Staphylococcus aureus in Diabetes.

Diabetic foot ulcer (DFU) is the most common and costly sequela of diabetes mellitus, often leading to lower-extremity amputation with poor 5-year survival rates. Staphylococcus aureus is the most prevalent pathogen isolated from DFU, suggesting adaptation of S. aureus to the unique metabolic conditions of diabetes. Diabetes is a complex metabolic disorder with increases not only in serum glucose levels but also in levels of other sugars, including fructose, mannose, and glucose-6-phosphate (G6P). However, the effect of metabolism of these sugars on the pathogenesis of S. aureus is not fully understood. In this study, we demonstrated that metabolism of G6P, fructose, and mannose induced greater expression of staphylococcal virulence factors than did glucose metabolism, but only G6P effects were independent of glucose-mediated carbon catabolite repression, suggesting a physiologically relevant role in diabetes. Our in vivo studies further demonstrated that G6P was highly present in skin adipose tissues of diabetic TALLYHO/JngJ mice, and subcutaneous infection with S. aureus caused significantly greater tissue necrosis and bacterial burden, compared to nondiabetic SWR/J mice. Finally, enhanced pathogenesis of S. aureus in diabetic TALLYHO/JngJ mice was significantly attenuated by deletion of the hexose phosphate transport (HPT) system. These results suggest that G6P is an important metabolic signal for S. aureus, enhancing the virulence in diabetes. A better understanding of how G6P metabolism is linked to the virulence of S. aureus will lead to the development of novel alternative therapeutics. IMPORTANCE Sugars are essential nutrients for S. aureus to survive and proliferate within the host. Because elevated serum glucose levels are a hallmark of diabetes, most studies have focused on the effect of glucose metabolism, and very little is known regarding the effects of metabolism of other sugars on the pathogenesis of S. aureus in diabetes. In this study, we demonstrated that G6P, which is highly present in diabetes, can induce expression of staphylococcal virulence factors that cause severe tissue necrosis and bacterial burden in skin infections. Our results highlight the importance of nutritional control of blood sugar levels, not only glucose but also other highly metabolizable sugars such as G6P. A better understanding of how activation of the HPT system is linked to the virulence of S. aureus will guide development of novel alternative therapeutics.

Úlcera genital imitadora / Misleading Genital Ulcer

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Recurrent Genital Ulcers.

Papulonecrotic tuberculid represents a hypersensitivity reaction to Mycobacterium tuberculosis or its products that disseminate through hematogenous route to the skin from an internal tuberculous focus. It is characterized by recurrent eruptions of asymptomatic, dusky red papules, which undergo ulceration and crusting, and eventually heal after a few weeks with varioliform scarring. Although it most commonly involves extragenital sites, isolated glans penis involvement has been reported very rarely.

Yersinia pseudotuberculosis infection with severe localised inflammation and ulceration of the ileum in a heart transplant patient.

In this case, we present an uncommon gastrointestinal infection in an immunocompromised patient that was solely diagnosed because of close collaboration between treating physicians and microbiologists. The patient is a 42-year-old male who underwent heart transplantation 5 years earlier. He presented with fever, weight loss, diarrhoea and tiredness. Initial investigations could not elucidate the aetiology of his symptoms. The patient was referred to the department of infectious diseases for further evaluation. Serology for Yersinia species was ordered and the result was suggestive for the possibility of a Yersinia species infection. Close collaboration between treating physicians and microbiologists followed and led to additional investigations, which revealed the diagnosis of a Yersinia pseudotuberculosis infection with extensive lesions in the gastrointestinal tract. Treatment with ciprofloxacin resulted in complete resolution of symptoms and healing of the gastrointestinal lesions. In conclusion, this case underlines the need for a multidisciplinary approach to complex patients of which symptoms have yet to be understood.

Immunization with nontreponemal antigen alters the course of experimental syphilis in the rabbit model.

The role of nontreponemal antibodies in the Treponema pallidum infection course is unclear. We investigated the effect of immunization with nontreponemal antigen on T. pallidum-challenged rabbits. Nontreponemal antigen was injected intravenously into rabbits in the nontreponemal group (n = 12) to elicit antibodies (≥1:64), and normal saline-injected rabbits were used as controls (n = 12). Then, rabbits were challenged with 106T. pallidum per site along their back. Lesion development was observed, and the injection sites were biopsied for mRNA analysis every week. Six rabbits from both groups were euthanized at 14 d and 28 d. The popliteal lymph nodes were extracted to assess infectivity using a rabbit infectivity test. The maximum lesion diameters were not different between the two groups (12.4 ± 0.9 mm in the nontreponemal group vs. 12.5 ± 1.0 mm in the control group, P = 0.386), but the time to maximum diameter appearance was delayed by approximately 4 d in the nontreponemal group (14.4 ± 1.6 d vs. 10.8 ± 1.9 d, P = 0.000). There were no significant differences in the proportions of lesions (58/60 (96.7%) vs. 59/60 (98.3%), P = 0.500) or ulcers (55/60 (91.7%) vs. 57/60 (95.0%), P = 0.359) between the two groups. An ulcer development delay of 5 d was observed in the nontreponemal group (19.3 ± 2.0 d vs. 14.0 ± 1.8 d, P = 0.000). IL-2 and IFN-γ mRNA expression in the nontreponemal group was significantly higher than that in the control group at 7 d and 14 d post-challenge. flaA mRNA expression and the rabbit infectivity test positive rate were not different between the two groups. Immunization with nontreponemal antigen altered the syphilis course in rabbits, resulting in delayed maximal lesion diameter and ulcer development, but it could not inhibit the spread of T. pallidum from primary lesion sites to viscera.

Effect of antibiotic-loaded chitosan nanodroplets on Enterococci isolated from chronic ulcers of the lower limbs.

Aim: To investigate the effect of a new platform of nanocarriers, called nanodroplets (NDs), to enhance the in vitro activity of vancomycin (Vm), against bacterial colonies isolated from chronic ulcers of the lower limbs. Materials & methods: Oxygen-loaded nanodroplets (OLNDs) or oxygen-free nanodroplets (OFNDs) were loaded with Vm (Vm-OLNDs and Vm-OFNDs). MIC and minimal bactericidal concentrations were evaluated for Vm, OLNDs and OFNDs loaded with Vm, OLNDs and OFNDs. Results & conclusion: Nanodroplets, either with or without oxygen, appeared as a suitable platform of antibiotic nanocarriers to enhance the antibacterial effects of Vm against Enterococci, with a decrease in both MIC and minimal bactericidal concentration against Vm-resistant Enterococci strains.

Sexually Transmitted Infections: Part I: Genital Bumps and Genital Ulcers.

Sexually transmitted infections (STIs) affect young people in a disproportionate way, with more than half of the infections occurring in 15- to 25-year-olds, although as an age group they constitute only 25% of the sexually active population. Pediatricians should be familiar with the social, behavioral, and biological factors that predispose adolescents to STIs. Preventive visits for teens and pre-teens should incorporate education and counseling about sexuality, safe sexual behavior, and STIs. Pediatricians should be able to identify, diagnose, and manage STIs presenting as genital "bumps" and genital "ulcers." Pediatricians should also offer human immunodeficiency virus testing and expedited partner treatment to all adolescents who are diagnosed as having an STI.

The use of irradiated amnion dressing for the treatment of antibiotic-disinfected skin ulcer.

Skin ulcers are non-healed wounds caused by inflammation of epidermis up to the dermis, which causes pain and limits body movements, significantly reducing quality of life. Amniotic membrane is a placental collagenous biomaterial with many biological and mechanical properties important for tissue engineering and regenerative medicine. The aim of this work is to evaluate the efficacy of topical antibiotic washing followed with irradiated human amniotic membrane (iHAM) dressing for treating five different types of ulcers. The current study included 15 patients who were recruited from the outpatient clinic of the Egyptian Atomic Energy Authority. Follow up of all treated cases that completed the regimen was up to 3 months. The clinical progression of all treated ulcers was quantitatively evaluated by computerized estimation of the wound size reduction based on 3D image analysis. All cases in this study showed great outcomes within several weeks of treatment depending on wound infection, ulcer depth and size, period of healing disorder, age, blood glycemia, and other clinical criteria. Patients' questionnaires revealed that pain was controlled by the first time of treatment. After 1 week post-treatment, granulation tissue was generated and observed in all patients, and all microbial colonies have been eliminated from wounds with previous infection. The current study indicated that the dressing of ulcers with iHAM induces fast healing without complication.

Long-term ulcerations caused by Mycobacterium lepromatosis.

Patients with leprosy rarely present ulcerated lesions that can appear during reactional states like Lucio's phenomenon (LP), as in our case. LP is a rare complication of multibacillary leprosy due to massive bacilli invasion of endothelial cells causing a thrombotic syndrome. The initial macular lesion is purpuric followed by multiple infiltrated papules and nodules, some of them ulcerated, associated to loss of sensation on lower limbs. The importance of recognizing ulcers as a specific cutaneous manifestation of leprosy allows early diagnosis and treatment, and therefore avoiding the development of disabilities and persistence of illness. Infection by Mycobacterium lepromatosis is associated with LP and it should be especially sought in patients from endemic areas.

Reproductive system infections in women: lower genital tract syndromes.

Gynecological and obstetrical infectious diseases are an important component of women's health. A system approach to gynecological and obstetrical infection helps unify and classify microbial etiology and pathogenesis within a clinical anatomical framework of lower and upper genital tract syndromes. The reproductive system of women includes the vulva, vagina, cervix, uterus, fallopian tubes and ovaries. During pregnancy, additional tissues include the chorioamnion and placenta together with the fetus and amniotic fluid. We review in two parts reproductive system infection syndromes in women using selected research results to illustrate the clinical utility of the system approach in terms of diagnosis, treatment and prevention. We conclude that a reproductive system perspective will lead to improvements in understanding, management and prevention of these diseases.

Pseudomonas piscis sp. nov., isolated from the profound head ulcers of farmed Murray cod (Maccullochella peelii peelii).

A Gram-stain-negative, strictly aerobic, motile, rod-shaped bacterium with monopolar flagella, designated as MC042T, was isolated from the profound head ulcers of farmed Murray cod sampled from Zhejiang Province, China. Analysis of its 16S rRNA gene sequence and multilocus sequence analysis phylogeny showed that strain MC042T belonged to the genus Pseudomonas, showing the highest 16S rRNA gene sequence similarity to Pseudomonas juntendi BML3T (98.9 %), and less than 98.8 % similarity to other Pseudomonas species with validly published names. Whole-genome sequencing and phylogenetic reconstruction based on a core set of 1563 Pseudomonas genes further indicated that strain MC042T was most closely related to the clade formed by Pseudomonas protegens CHA0T and Pseudomonas saponiphila DSM 975T and distantly related to any of the validly published species of the genus Pseudomonas. Furthermore, strain MC042T could be distinguished from its closely related species of the genus Pseudomonas by its ability to assimilate maltose, d-xylose and melibiose, but not d-mannitol. The principal fatty acids were C16 : 0, summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1ω7c) and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The respiratory quinone was Q-9. Polar lipids of strain MC042T comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, unidentified glycolipids, an unidentified lipid, an unknown glycolipid and aminolipid. Based on its phenotypic, chemotaxonomic and phylogenetic features, strain MC042T is considered to represent a novel species, for which the name Pseudomonas piscis sp. nov. is proposed. The type strain is MC042T (=KCTC 72033T=MCCC 1K03575T).

The rash with mucosal ulceration.

A rash is a disseminated eruption of cutaneous lesions with great variation in appearance, cause, and severity. When the physician is facing a rash, the history and physical examination of the patient are extremely important for the identification of the disease and its causal agent. There are various causes for a rash, which may be infectious, allergic, or rheumatologic, besides many others. Rashes associated with mucosal ulcers may have causes related to viral and bacterial infections or drug reactions. They may be associated with measles; erythema infectiosum; roseola infantum; rubella; hand, foot, and mouth disease; pityriasis rosea; dengue fever; chikungunya; zika; scarlet fever; meningococcal diseases; syphilis; and exanthematous drug eruptions.

Evolutionary trends in bacteria isolated from moderate and severe diabetic foot infections in a Portuguese tertiary center.

INTRODUCTION: Diabetic Foot infections (DFI) are a major cause of hospitalization in patients with diabetes. The microbiological study of diabetic ulcers is essential to adequate antibiotic therapy and to minimize the selection of resistant microorganisms. The aim of this study was to characterize and to compare the evolution of isolated microorganisms between the biennium 2010-2011 and 2016-2017, in hospitalized patients with DFI. MATERIAL AND METHODS: Retrospective evaluation of the clinical and analytical data of patients who were admitted due to DFI in 2010-2011 (group 2010/11) and 2016-2017 (group 2016/17). Only the first hospitalization for each patient was included. An adequate descriptive and comparative statistical analysis was performed. RESULTS: There were 274 admissions due to DFI, 151 in 2010/11 and 123 in 2016/17. There was an increase in admissions due to neuroischemic DFI (51.0% in 2010/11 to 61.8% in 2016/17, p = 0.048). Staphylococcus aureus (SA) was the most common isolate in 2010/11 (26.7%). In 2016/17 most cultures were mixed polymicrobial and isolation of Enterobacteriaceae and Pseudomonas aeruginosa increased from 2010/11 to 2016/17 (15.9% to 30.6%, p = 0.001, and 9.1% to 13.7%, p = 0.048, respectively). CONCLUSION: There was an increase in the prevalence of neuroischemic DFU. The Enterobacteriaceae family replaced SA as the most prevalent pathogen in DFI, with an increase in the isolation of gram-negative microorganisms and mixed polymicrobial cultures. Chronic neuroischemic infected ulcers usually present distinct bacterial isolates; knowledge about the most common agents is warranted in order to better select empiric antibiotic therapy.

Correlation between healing type of lesion and recurrence in gastric neoplastic lesions after endoscopic submucosal dissection.

BACKGROUND/AIMS: To date, there are few reports on the clinical association between healing pattern of lesion and local recurrence after endoscopic resection (ER). We examined the risk factors associated with local recurrence after endoscopic submucosal dissection (ESD) and the correlation between healing type of lesion and recurrence. MATERIALS AND METHODS: We retrospectively analyzed medical records of 293 patients who underwent ESD of early gastric cancer or gastric adenoma between April 2010 and January 2012. We analyzed the relationship among factors such as age, location of lesion, size, pathologic diagnosis, presence of Helicobacter pylori (H. pylori), and healing types of ulcers in patients with local recurrence through follow-up endoscopic surveillance (1, 6, and 12 months after ESD). RESULTS: We analyzed 141 patients except for patients who had not undergone surveillance endoscopy, H. pylori test, and ambiguous healing patterns. There were no significant correlations between local recurrences concerning sex, age, tumor size, location, and pathologic diagnosis. When the healing type of the ulcer was divided into hypertrophic polypoid type (9 cases (6.4%)), scar type (122 cases (86.5%)), and nodular type (10 cases (7.1%)), the scar type was found to be most common. A total of eight patients (5.7%) developed local recurrence, of which five were of nodular type and statistically significant (p=0.000). CONCLUSION: The most common type of ulcer healing was scar type after ESD, but nodular type was associated with local recurrence. When we perform follow-up endoscopy after ESD, we should pay attention to the lesion that has nodular change of mucosal surface.

Arthrobacter ulcerisalmonis sp. nov., isolated from an ulcer of a farmed Atlantic salmon (Salmo salar), and emended description of the genus Arthrobacter sensu lato.

A Gram-stain positive, pleomorphic, oxidase-negative, non-motile isolate from the ulcer of a farmed Atlantic salmon (Salmo salar), designated strain T11bT, was subjected to a comprehensive taxonomic investigation. A comparative analysis of the 16S rRNA gene sequence showed highest similarities to the type strains of Pseudarthrobacter siccitolerans (98.1 %) and Arthrobacter methylotrophus and Pseudarthrobacter phenanthrenivorans (both 98.0 %). The highest ANI value observed between the assembled genome of T11bT and the publicly available Pseudarthrobacter and Arthrobacter type strain genomes were 81.15 and 80.99 %, respectively. The major respiratory quinone was menaquinone MK-9(H2). The polyamine pattern contained predominantly spermidine. The polar lipid profile consisted of the major lipids diphosphatidylglycerol, phosphatidylglycerol, monogalactosyl-diacylglycerol and dimannosylglyceride. Minor amouts of trimannosyldiacylglycerol and phosphatidylinositol were also detected. The peptidoglycan was of the type A3α l-Lys-l-Ser-l-Thr-l-Ala (A11.23). In the fatty acid profile, anteiso and iso branched fatty acids predominated (anteiso C15 : 0, iso C16 : 0, anteiso C17 : 0). Moderate to low DNA-DNA similarities, physiological traits as well as unique traits in the fatty acid pattern distinguished strain T11bT from the next related species. All these data point to the fact that strain T11bT represents a novel species of the genus Arthrobacter for which we propose the name Arthrobacter ulcerisalmonis sp. nov. The type strain is T11bT (=CIP 111621T=CCM 8854T=LMG 30632T=DSM 107127T).