Radiological presentation of active pulmonary tuberculosis in kidney transplant recipients: a retrospective study of four cases and a review of the literature.

Although kidney transplantation is the best therapeutic option for patients with chronic kidney disease, the immunosuppression required greatly increases susceptibility to infections that are responsible for high post-transplant mortality. Pulmonary tuberculosis (TB) represents a major cause of such infections, and its early diagnosis is therefore quite important. In view of that, we researched the manifestations of active pulmonary TB in kidney transplant recipients, through chest X-ray and computed tomography (CT), as well as determining the number of cases of active pulmonary TB occurring over a 3.5-year period at our institution. We identified four cases of active pulmonary TB in kidney transplant recipients. The CT scans provided information complementary to the chest X-ray findings in all four of those cases. We compared our CT findings with those reported in the literature. We analyzed our experience in conjunction with an extensive review of the literature that was nevertheless limited because few studies have been carried out in lowand middle-income countries, where the incidence of TB is higher.

Apesar de o transplante renal ser a melhor opção terapêutica para pacientes com doença renal crônica, a imunodepressão decorrente desse tratamento eleva muito a suscetibilidade desses pacientes a infecções, responsáveis por altas taxas de mortalidade pós-operatórias. A tuberculose (TB) pulmonar é uma significativa causa dessas infecções, sendo muito importante o seu diagnóstico precoce. Assim, nós pesquisamos as manifestações da TB pulmonar ativa nessa população de transplantados renais por meio de radiografias simples e tomografia computadorizada (TC) do tórax, também para estabelecer o número de casos de TB pulmonar ativa em nossa instituição após levantamento de 3,5 anos. Encontramos quatro casos de TB pulmonar ativa em pacientes transplantados renais. A TC forneceu informações adicionais em relação às radiografias de tórax em 100% dos casos analisados. Comparamos os nossos achados de TC com os relatados na literatura. Somamos a experiência obtida com extensa revisão da literatura, ainda limitada nessa questão, com poucos estudos realizados em países em desenvolvimento onde a incidência de TB é maior.

Evaluation of Torque Teno Virus DNA Load as a Predictive Biomarker in Kidney Transplant Recipients Converted from Calcineurin Inhibitors to Belatacept.

Introduction: Belatacept is a relevant alternative to calcineurin inhibitors (CNIs) after kidney transplantation (KT). Circulating Torque Teno virus (TTV) DNA load is correlated to infections and rejection risks post-KT in patients treated with CNIs. The aim of this study was to assess the TTV DNA load profile in kidney transplant recipients converted from CNIs to belatacept and explore its use as a predictive biomarker. Methods: Sixty-eight single-center kidney transplanted recipients who were converted from CNIs to belatacept between June, 2015 and December, 2020 were included in this study. Whole blood TTV DNA load was measured before, at 3, 6, and 12 months post-belatacept conversion. Our primary end point was to assess the TTV DNA load profile and correlate the results with rejection and opportunistic infection (OPI). Results: TTV DNA load remained stable after belatacept conversion, that is, 3.8 (3.1-4.9), 4.4 (3.2-5.4), 4.0 (3.0-5.7) and 4.2 (3.0-5.2) log10 copies/ml at baseline, 3, 6, and 12 months, respectively. No correlation was found between TTV DNA load and post-KT complications. Chronic allograft dysfunction at 1 year postconversion was associated with a lower TTV DNA load after 6 and 12-months (P = 0.014 and P = 0.021, respectively). A higher TTV DNA load was found in older patients and in those with higher body mass index (BMI) (P = 0.023 and P = 0.005, respectively). Conclusion: Conversion from CNIs to belatacept did not affect TTV DNA load. OPIs or acute rejection occurrences were not associated with TTV DNA load. However, low TTV (lTTV) DNA load after 6 months postconversion may be a promising tool to predict graft dysfunction risk at 1-year postconversion.

Ochrobactrum anthropi sepsis in a 15-month-old child: A case report.

Key Clinical Message: Ochrobactrum anthropi (O. anthropi), a rare opportunistic pathogen, caused sepsis in a malnourished 15-month-old African child. Early detection and appropriate antibiotics led to full recovery, highlighting the importance of robust surveillance for emerging pathogens in vulnerable populations. Abstract: While rarely causing infections, O. anthropi, a non-fermenting, obligately aerobic, flagellated gram-negative bacillus, demonstrates oxidase positivity and indole negativity. Traditionally, Ochrobactrum spp is considered a low threat due to its environmental abundance and mild virulence. It is, however, a multidrug-resistant bacteria known for causing opportunistic infections in humans. O. anthropi is typically associated with catheter-related bloodstream infections. The first documented case was in 1998; most cases have been reported in developed countries. We present a case of O. anthropi sepsis in a malnourished child in sub-Saharan Africa. We report a case involving a 15-month-old African female who presented with symptoms and signs of protein-energy malnutrition and sepsis. The blood culture revealed O.anthropi. We treated the child with the empirical first-line antibiotics per the national guidelines, intravenous ampicillin and gentamicin for a week, and the child fully recovered. This report describes a rare case of O. anthropi sepsis with malnutrition in an African female child. O. anthropi is an emerging pathogen causing opportunistic infections in both immunocompetent and immunocompromised patients. We report that early bacterial detection, appropriate antibiotic susceptibility and antimicrobial management based on local antibiogram data may be essential for excellent patient outcomes. Additionally, we recommend more robust surveillance to detect such rare emerging pathogens.

Opportunistic Infections and Malignancies in a Patient With HIV/AIDS and a Critically Low CD4 Count of 1 Cell/µL.

We present a 45-year-old African American male with a medical history of advanced-stage HIV/AIDS (CD4 count: 1 cell/µL) and poor adherence to highly active antiretroviral therapy (HAART), who presented with symptoms of diarrhea, weakness, and respiratory distress. Upon admission, duodenal and colonic biopsies revealed a diffuse histiocytic infiltrate consistent with Mycobacterium avium complex (MAC), and a cecal biopsy was positive for Kaposi sarcoma (KS). Further workup showed consolidation and a right pleural effusion on chest X-ray, suggesting a pneumonia infection. The patient's hypoglycemic state and lung consolidation raised concerns for sepsis, despite negative blood cultures for the first 24 hours. The patient was initiated on HAART and treated with azithromycin, rifabutin, and ethambutol for disseminated MAC. Despite the aggressive immunotherapy, the patient's condition did not improve, and he eventually expired. This case uniquely highlights the wide range of opportunistic infections and malignancies that can present in individuals with advanced-stage HIV/AIDS, underscoring the importance of early recognition and treatment. This susceptible demographic warrants further research due to the non-solidified prognosis of individuals with severe immunodeficiency.

A Silent Threat Unveiled: Invasive Fungal Sinusitis in a High-Risk Hematologic Malignancy Patient.

Invasive fungal sinusitis (IFS) poses a fatal threat to patients with hematological malignancies or a history of allogeneic hematopoietic stem cell transplant (HSCT). While invasive aspergillosis, a subtype of IFS, remains rare in immunocompetent individuals, allogeneic HSCT recipients face a notable surge in incidence. Despite the rapid onset and progression of IFS, its clinical presentation is subtle, contributing to heightened mortality rates. Prompt surgical debridement and systemic antifungal therapy are required to yield positive results. Examining IFS cases in HSCT recipients is vital, providing insights into its clinical course, prevention strategies, and improved evaluation. We present a rare presentation of IFS with Aspergillus niger in a relapsed acute myeloid leukemia patient post-HSCT. Two weeks after chemotherapy, the patient developed headaches and blood-tinged sinus drainage in the setting of pancytopenia. Radiologic and pathological findings confirmed the diagnosis of IFS, necessitating weeks of intensive anti-fungal therapy. Despite the initial positive response, the disease ultimately progressed to a fatal outcome. This case emphasizes that early detection is required for a favorable treatment response. Furthermore, it underscores the importance of heightened clinical suspicion, risk stratification, multidisciplinary care, and ongoing research for optimal management of IFS in allogeneic HSCT recipients.

A Prolonged Case of Severe Mpox as an Opportunistic Infection in Advanced AIDS.

The case report discusses a 29-year-old male with advanced HIV who experienced one of the longest, confirmed cases of monkeypox (mpox) infection. Despite treatment with antivirals and supportive care, including intravenous tecovirimat and vaccinia immune globulin, the patient's condition worsened over a six-and-a-half-month period. He suffered from widespread ulcerative, necrotic lesions and multiple complications, including acute kidney injury, multi-drug resistant bacterial infections, and respiratory failure. Despite repeated treatments, including brincidofovir, the patient remained PCR-positive for monkeypox virus (MPXV) with low cycle threshold (Ct) values, indicating active infection. The case underscores the severity of mpox in immunocompromised individuals, particularly those with advanced HIV, and highlights the challenges in managing such cases. The patient's persistently low CD4 count and unsuppressed HIV viral load likely contributed to the inability to clear the virus. The report emphasizes the need for further research to optimize treatment strategies for MPXV infection, especially in people living with HIV.

Case report: Experience and insights on the treatment of two cases of cryptococcal meningitis during the later stages of the COVID-19 pandemic.

In the late stages of the COVID-19 pandemic, there's an increasing trend in opportunistic infections, including bacterial and fungal infections. This study discusses the treatment process of two cases of cryptococcal meningitis during the COVID-19 pandemic. It highlights the importance of laboratory testing for these co-infections and stresses the need for vigilance, early diagnosis, and proactive treatment to improve patient outcomes in the post-pandemic era.

Drug-resistant oral candidiasis in patients with HIV infection: a systematic review and meta-analysis.

BACKGROUND: Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients. METHODS: Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model. RESULTS: Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I2 > 50.00%, P < 0.01), except for caspofungin (I2 = 0.00%, P = 0.65). CONCLUSIONS: Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin. REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).

Balancing Bioresponsive Biofilm Eradication and Guided Tissue Repair via Pro-Efferocytosis and Bidirectional Pyroptosis Regulation during Implant Surgery.

There is an increasingly growing demand to balance tissue repair guidance and opportunistic infection (OI) inhibition in clinical implant surgery. Herein, we developed a nanoadjuvant for all-stage tissue repair guidance and biofilm-responsive OI eradication via in situ incorporating Cobaltiprotoporphyrin (CoPP) into Prussian blue (PB) to prepare PB-CoPP nanozymes (PCZs). Released CoPP possesses a pro-efferocytosis effect for eliminating apoptotic and progressing necrotic cells in tissue trauma, thus preventing secondary inflammation. Once OIs occur, PCZs with switchable nanocatalytic capacity can achieve bidirectional pyroptosis regulation. Once reaching the acidic biofilm microenvironment, PCZs possess peroxidase (POD)-like activity that can generate reactive oxygen species (ROS) to eradicate bacterial biofilms, especially when synergized with the photothermal effect. Furthermore, generated ROS can promote macrophage pyroptosis to secrete inflammatory cytokines and antimicrobial proteins for biofilm eradication in vivo. After eradicating the biofilm, PCZs possess catalase (CAT)-like activity in a neutral environment, which can scavenge ROS and inhibit macrophage pyroptosis, thereby improving the inflammatory microenvironment. Briefly, PCZs as nanoadjuvants feature the capability of all-stage tissue repair guidance and biofilm-responsive OI inhibition that can be routinely performed in all implant surgeries, providing a wide range of application prospects and commercial translational value.

Multiple Myeloma: A Review of the Literature and a Case Report Highlighting the Immunocompromised State of Myeloma Patients.

Multiple myeloma (MM), a malignancy involving plasma cells, disproportionately affects older adults with an average age of diagnosis of about 70 years. Oftentimes, the therapies used in the treatment of MM are associated with a risk for immunotoxicity, lowering the ability of the immune system to fight off opportunistic infections. This is an important relationship for clinicians to realize as the incidence of opportunistic infections in myeloma patients is increasing. As an example, we present a case of a patient with MM who subsequently developed a cryptococcal infection. Our paper will highlight the key details of the case as well as shed light on the importance of understanding the immunodeficiencies in this patient population. We highlight important aspects of the current literature related to MM and relate them to the associated case.

Comparison of different lateral flow assays on bronchoalveolar lavage fluid for invasive aspergillosis screening in non-hematological patients.

Several lateral flow assays (LFA) capable of detecting Aspergillus fumigatus in serum and broncho-alveolar lavage fluid (BALF) within the hour, thereby potentially accelerating the screening process, are now commercially available. We prospectively compared three LFA targeting A. fumigatus on BALF collected from non-surgical intensive care patients between June 2022 and February 2023. The three LFA tested were Sõna Aspergillus galactomannan LFA (Immy), Fungadia Aspergillus antigen (Gadia), and AspLFD (OLM Diagnostics). We compared the results of these LFA with those of the galactomannan (GM) Platelia Aspergillus enzyme immunoassay (Bio-Rad), culture on Sabouraud medium and Aspergillus qPCR. We tested 97 BALF samples from 92 patients. In total 84 BALF samples tested negative with all three LFA, and four BALF samples tested positive with the AspLFD assay only (OLM). Only one BALF sample tested positive with the three LFA. In addition, three BALF samples tested positive only with the GM Platelia immunoassay. Four diagnosis of probable invasive aspergillosis were retained for the 92 patients tested. This prospective series included very few positive samples. From a practical point of view, the LFA from OLM presented the simplest protocol for use.

Emerging Fungal Pathogen Rhodotorula Species Isolated From a Patient With a Lung Malignancy.

Rhodotorula is a genus of ubiquitous pigmented yeast found in the environment and as a commensal of human and animal microbiota. Previously considered nonpathogenic, Rhodotorula has emerged as an important cause of nosocomial and opportunistic infections in susceptible patients. While Rhodotorula spp. are common commensals in healthy individuals, the yeast may overgrow in patients with compromised immune systems causing disease. Herein, we provide a detailed presentation of a rare case involving a 79-year-old Caucasian female with a lung malignancy who developed massive cavitations in her lungs. The patient's lung tissue was cultured and grew an unidentified species of the genus Rhodotorula. The patient's health declined rapidly, and she expired due to hypoxemia. Clinicians must recognize patient groups potentially at risk for infection with Rhodotorula spp. Early identification and initiation of appropriate interventions are crucial in reducing mortality associated with this opportunistic fungal infection.

Survival After Hematopoietic Stem Cell Transplantation in Severe Combined Immunodeficiency (SCID): A Worldwide Review of the Prognostic Variables.

This study aims to perform an extensive review of the literature that evaluates various factors that affect the survival rates of patients with severe combined immunodeficiency (SCID) after hematopoietic stem cell transplantation (HSCT) in developed and developing countries. An extensive search of the literature was made in four different databases (PubMed, Embase, Scopus, and Web of Science). The search was carried out in December 2022 and updated in July 2023, and the terms such as "hematopoietic stem cell transplantation," "bone marrow transplant," "mortality," "opportunistic infections," and "survival" associated with "severe combined immunodeficiency" were sought based on the MeSH terms. The language of the articles was "English," and only articles published from 2000 onwards were selected. Twenty-three articles fulfilled the inclusion criteria for review and data extraction. The data collected corroborates that early HSCT, but above all, HSCT in patients without active infections, is related to better overall survival. The universal implementation of newborn screening for SCID will be a fundamental pillar for enabling most transplants to be carried out in this "ideal scenario" at an early age and free from infection. HSCT with an HLA-identical sibling donor is also associated with better survival rates, but this is the least common scenario. For this reason, transplantation with matched unrelated donors (MUD) and mismatched related donors (mMRD/Haploidentical) appear as alternatives. The results obtained with MUD are improving and show survival rates similar to those of MSD, as well as they do not require manipulation of the graft with expensive technologies. However, they still have high rates of complications after HSCT. Transplants with mMRD/Haplo are performed just in a few large centers because of the high costs of the technology to perform CD3/CD19 depletion and TCRαß/CD19 depletion or CD34 + selection techniques in vitro. The new possibility of in vivo T cell depletion using post-transplant cyclophosphamide could also be a viable alternative for performing mMRD transplants in centers that do not have this technology, especially in developing countries.

Microsporum canis pseudomycetoma and disseminated Mycobacterium genavense infection in an HIV/AIDS patient, an unusual combination.

Pseudomycetomas are rare fungal subcutaneous infections caused by dermatophytes, which are mainly observed in immunocompromised patients. Mycobacterium genavense is considered an opportunistic pathogen in people living with HIV/AIDS (PLWHA), clinically resembling the presentation of Mycobacterium avium complex (MAC). Here, we describe the case of a 26-year-old PLWHA with a 3-month history of a 4cm tumoral, duroelastic and painful lesion located on the back. Histopathology of the tumoral lesion revealed chronic granulomatous inflammation with grains composed of PAS-positive and Grocott-positive septate hyphae, as well as acid-fast bacilli (AFB). Culture on Sabouraud and lactrimel agar developed colonies that were later identified as Microsporum canis. In successive samples, the AFB were identified as M. genavense by restriction analysis of PCR products. Immunocompromised PLWHA not only suffer increased susceptibility to diseases due to unusual pathogens but also atypical clinical presentation of frequently encountered pathogens.

Incidence and Predicting Factors of Opportunistic Infections after Antiretroviral Therapy Initiation among Treatment-naïve Patients with HIV Infection: A Retrospective Cohort Study in A Tertiary Care Hospital.

OBJECTIVES: To determine the incidence of opportunistic infections (OIs) and the predictive factors for the development of OIs after antiretroviral therapy (ART) initiation among treatment-naïve patients with HIV infection. RESULTS: Of 401 HIV-infected patients, 38 (9.5%) HIV-infected patients developed OIs after initiating ART, with an incidence rate of 25.6/1000 person-years. The median time (IQR) from ART initiation to OI occurrence was 26.5 (14-73) days. In multivariate Cox proportional hazard regression, body mass index ≤18.5 kg/m2 (adjusted hazard ratio [aHR] 2.28, 95% confidence interval [CI] 1.18-4.42, P = .015), symptoms at presentation (aHR 13.59, 95% CI 3.24-56.9, P < .001), serum glutamate-pyruvate transaminase >55 U/L (aHR 2.09, 95% CI 1.06-4.15, P = .035), and initiation of a dolutegravir-based regimen (aHR 4.39, 95% CI 1.54-12.48, P = .006) were significantly associated with OIs after ART initiation. CONCLUSION: OIs after ART initiation are common. Malnutrition, symptomatic presentation, abnormal liver enzymes, and DTG-based regimens are predictors of OI occurrence after ART initiation. Physicians must monitor and appropriately treat OIs after ART initiation.

Implementation of a rapid diagnostic assay package for cryptococcosis, histoplasmosis and tuberculosis in people living with HIV in Paraguay.

BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm3). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.

Next-Generation Sequencing-Based Identification of Enterobacter hormaechei as Causative Agent of High Mortality Disease in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) Mice.

NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice, lacking many components of a mature immune system, are at increased risk of disease. General understanding of potential pathogens of these mice is limited. We describe a high mortality disease outbreak caused by an opportunistic bacterial infection in NSG mice. Affected animals exhibited perianal fecal staining, dehydration, and wasting. Histopathologic lesions included a primary necrotizing enterocolitis, with inflammatory and necrotizing lesions also occurring in the liver, kidneys, heart, and brain of some mice. All affected individuals tested negative for known opportunistic pathogens of immunodeficient mice. We initially identified a member of Enterobacter cloacae complex (ECC) in association with the outbreak by traditional diagnostics. ECC was cultured from extraintestinal organs, both with and without histopathologic lesions, suggesting bacteremia. Infrared spectroscopy and MALDI-TOF mass spectrometry demonstrated that isolates from the outbreak shared molecular features and likely a common origin. We subsequently hypothesized that advanced sequencing methods would identify a single species of ECC associated with clinical disease. Using a novel targeted amplicon-based next-generation sequencing assay, we identified Enterobacter hormaechei in association with this outbreak. Knowledge of this organism as a potential opportunistic pathogen in NSG mice is critical for preclinical studies to prevent loss of animals and confounding of research.

Tetramerization is essential for the enzymatic function of the Pseudomonas aeruginosa virulence factor UDP-glucose pyrophosphorylase.

Multidrug-resistant bacteria such as the opportunistic pathogen Pseudomonas aeruginosa, which causes life-threatening infections especially in immunocompromised individuals and cystic fibrosis patients, pose an increasing threat to public health. In the search for new treatment options, P. aeruginosa uridine diphosphate-glucose pyrophosphorylase (PaUGP) has been proposed as a novel drug target because it is required for the biosynthesis of important virulence factors and linked to pathogenicity in animal models. Here, we show that UGP-deficient P. aeruginosa exhibits severely reduced virulence against human lung tissue and cells, emphasizing the enzyme's suitability as a drug target. To establish a basis for the development of selective PaUGP inhibitors, we solved the product-bound crystal structure of tetrameric PaUGP and conducted a comprehensive structure-function analysis, identifying key residues at two different molecular interfaces that are essential for tetramer integrity and catalytic activity and demonstrating that tetramerization is pivotal for PaUGP function. Importantly, we show that part of the PaUGP oligomerization interface is uniquely conserved across bacterial UGPs but does not exist in the human enzyme, therefore representing an allosteric site that may be targeted to selectively inhibit bacterial UGPs.IMPORTANCEInfections with the opportunistic bacterial pathogen Pseudomonas aeruginosa are becoming increasingly difficult to treat due to multidrug resistance. Here, we show that the enzyme uridine diphosphate-glucose pyrophosphorylase (UGP) is involved in P. aeruginosa virulence toward human lung tissue and cells, making it a potential target for the development of new antibacterial drugs. Our exploration of P. aeruginosa (Pa)UGP structure-function relationships reveals that the activity of PaUGP depends on the formation of a tetrameric enzyme complex. We found that a molecular interface involved in tetramer formation is conserved in all bacterial UGPs but not in the human enzyme, and therefore hypothesize that it provides an ideal point of attack to selectively inhibit bacterial UGPs and exploit them as drug targets.

Acute Cytomegalovirus Colitis Presenting As Exacerbation of Ulcerative Colitis: A Case Report.

This case report presents a 24-year-old female with a history of ulcerative colitis (UC) who sought care for symptoms initially suggestive of the disease exacerbation but was later diagnosed as acute cytomegalovirus (CMV) colitis. The patient's clinical course, marked by watery diarrhea, blood in stools, vomiting, and fever, raised suspicion of a UC flare. However, a nuanced diagnostic approach revealed CMV superinfection, including computed tomography, colonoscopy, and tissue polymerase chain reaction (PCR). The patient's immunosuppressive history, with prior treatment, including intravenous infliximab and azathioprine, contributed to CMV infection. Treatment involved initiation of tofacitinib and antiviral therapy with valganciclovir. This case underscores the diagnostic challenges in distinguishing between infectious complications and UC exacerbations, necessitating a tailored, multidisciplinary approach for optimal management. It highlights the delicate balance required when managing UC patients on immunosuppressive regimens, emphasizing the importance of timely diagnosis and individualized treatment strategies in complex clinical scenarios.