Search Results (512)

Staphylococcus aureus is a major opportunistic pathogen responsible for a wide spectrum of human infections, including severe and difficult-to-treat cases. The emergence of multidrug-resistant strains limits the efficacy of conventional antibiotic therapies and poses a significant global public health challenge. In this context, the search for novel antibiotics has intensified, with increasing interest in marine resources, an ecosystem still largely underexplored. Marine bacteria produce a vast array of secondary metabolites with unique structures and potentially novel modes of antibacterial action. Several compounds isolated from marine bacterial strains have demonstrated promising activity against multidrug-resistant S. aureus, including antivirulence effects such as biofilm formation and Quorum-Sensing inhibition. This review explores the potential of marine bacteria as a source of new antibiotics against S. aureus, discusses both classical and advanced strategies for the discovery of bioactive molecules, and highlights the scientific and technological challenges involved in translating these findings into clinical applications. Full article

Adherent-invasive E. coli (AIEC) is closely related to inflammatory bowel disease (IBD). However, its pathogenic mechanism has not yet been fully elucidated. Using a BLASTP search, we discovered that the amino acid sequence of a putative protein (UFP37798.1) in the AIEC LF82 strain is highly homologous to some regulators in the SlyA family. We named it EruA. We displayed the secondary structures of EruA using bioinformatics, overexpressed the His₆-tagged EruA protein using SDS-PAGE, and dissected the genetic organization of the eruA chromosomal region using 5′RACE. We constructed an eruA deletion mutant (ΔeruA) and a complementary strain (CΔeruA) of the LF82 strain. The transcriptomes of wild-type (WT) and ΔeruA bacteria were compared using RNA sequencing and qRT-PCR, thereby identifying 32 differentially expressed genes (DEGs). Based on YASARA software and EMSA analysis, EruA directly binds to the consensus sequences (P_fimA and P_tnaB) in the promoter region of the fimA and tnaB genes from these DEGs. By using a super-resolution confocal microscope (SCM), counting CFUs of colonies on plates, indole quantification, and crystal violet staining of biofilms adhered to tubes or 96-well plates, we found that EruA activates the fimA to promote bacterial adhesion to intestinal epithelial cells and activates the tnaB to enhance bacterial indole production and biofilm formation. Moreover, EruA helps AIEC resist environmental stress and enhances bacterial survival within macrophages as well as loading in mouse tissues. Notably, EruA promotes AIEC colonization in the colons of mice and exacerbates intestinal inflammation caused by bacterial infection in mice with DSS-induced inflammatory colitis, manifested by weight loss, colon length shortening, and pathological changes in colon tissues. Therefore, EruA plays a key role in the pathogenicity of AIEC. Full article

Introduction: The sustained global epidemic of Human Immunodeficiency Virus (HIV) necessitates comprehensive, region-specific surveillance to inform public health policy. This 30-year retrospective observational cohort study delineated the epidemiological patterns, transmission dynamics, treatment efficacy, and long-term clinical outcomes of HIV infection in Oman to strategically align preventative and therapeutic programs with Oman’s Vision 2040 framework. Methods: We analyzed the clinical and epidemiological data of 429 confirmed HIV-positive patients with a minimum follow-up period of six months, registered at a secondary care facility in North Batinah, Oman, between January 1995 and December 2024. Predictors of mortality were rigorously assessed utilizing Kaplan–Meier survival analysis and Cox proportional hazards regression models. Continuous variables were evaluated using independent sample t-tests or Mann–Whitney U tests, while categorical variables employed chi-square or Fisher’s exact tests. Results: The cohort exhibited a male predominance (70.6%) with a mean age at diagnosis of 32.8 years (SD ± 12.17). Heterosexual contact constituted the predominant mode of acquisition (56%), followed by bisexual (17%) and homosexual (12%) contacts. Although 67.1% of patients presented with early, asymptomatic disease (WHO Stage 1), opportunistic infections were evident in 28.1% of the cohort, with recurrent sepsis (8.4%) and bacterial pneumonia (3.5%) being the most frequent complications. The WHO clinical stage at presentation was confirmed as a highly significant predictor of survival (p < 0.0001). Stage 1 patients achieved excellent long-term prognosis (approximately 75% survival beyond 30 years), markedly contrasting with Stage 4 patients, whose survival declined sharply (median survival of approximately 8 years, and only 10–15% surviving past 20 years). The tenofovir/emtricitabine/efavirenz regimen showed superior efficacy, achieving 75% survival at 30 years, relative to zidovudine-based regimens, which showed significantly poorer performance (15–20% survival at 20 years). Conclusions: This investigation substantiates the shift toward predominant heterosexual transmission and emphasizes the critical prognostic significance of the clinical stage at diagnosis. Optimal long-term survival mandates prompt diagnosis, timely initiation of contemporary antiretroviral therapies, and sustained viral suppression. These findings offer crucial evidence to strengthen HIV prevention and treatment programs within Oman. Full article

Background and Objectives: Secondary bacterial infection drives poor outcomes in older adults with COVID-19, but age-specific microbiology and its interaction with severity scores are not well defined. We characterized respiratory and pleural pathogens, resistance profiles, and their impact on day-5 SOFA/APACHE II in octogenarians versus younger adults. Methods: We performed a retrospective cohort study of adults with RT-PCR-confirmed coronavirus disease 2019 (COVID-19) at a tertiary infectious diseases center (≥80 years, n = 152; <65 years, n = 327). Respiratory and pleural samples were processed according to EUCAST standards. Identification employed matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Pathogen distributions, susceptibilities, and rates of superimposed pneumonia, empyema, and bacteremia were compared by age, and associations between secondary pneumonia, day-5 SOFA/APACHE II, and 28-day mortality were analyzed. Results: Sputum was obtained in 67.1% of older and 65.7% of younger adults, with numerically higher culture positivity in older patients (73.5% vs. 65.1%). Pathogen spectra were similar, dominated by Streptococcus pneumoniae (24.0% vs. 24.3%), methicillin-susceptible Staphylococcus aureus (MSSA) (18.7% vs. 20.7%), methicillin-resistant Staphylococcus aureus (MRSA) (9.3% vs. 6.4%), and Klebsiella pneumoniae, including extended-spectrum β-lactamase (ESBL)-producing strains. Empyema was more frequent in octogenarians (7.9% vs. 3.1%), and pleural cultures were usually positive. Meropenem retained 100% activity against ESBL-producing K. pneumoniae and Pseudomonas in both strata. In ≥80-year-olds, superimposed pneumonia was associated with higher day-5 SOFA (6.6 vs. 5.5) and APACHE II (24.3 vs. 21.0) scores and markedly increased 28-day mortality (37.5% vs. 9.8%). Conclusions: In octogenarians with COVID-19, secondary bacterial pneumonia and empyema are frequent, microbiologically similar to younger adults, and strongly amplify organ dysfunction and mortality even with largely preserved carbapenem susceptibility. Full article

Bovine Respiratory Disease (BRD) represents one of the largest causes of economic loss and animal morbidity in the global cattle industry, second only to neonatal diarrhea. Its etiology is complex, originating from a multifactorial combination of host susceptibility, environmental stressors, viral infections, and secondary bacterial pathogens. Although viruses are often the initial cause of disease, suppressing the host’s respiratory defense mechanisms, most of the severe pneumonic damage and clinical signs can be attributed to bacterial infections. This review provides an overview of the primary bacterial agents identified within the BRD complex, including Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. We discuss their role as commensals that then become opportunistic pathogens, and further how they interact in a synergistic relationship with a primary viral insult, leading to the resulting pathogenesis and the development of pneumonia. This manuscript discusses in further detail some of the challenges in BRD management, such as the limitations of current diagnostic methodologies, overreliance on antimicrobial therapy, and the growing concern of antimicrobial resistance. Lastly, the need for integrated approaches in management, better husbandry and biosecurity, coupled with the development of novel therapeutic alternatives, is underlined as a means of assuring a sustainable control of this serious syndrome. Full article

Background and Clinical Significance: Furuncular myiasis is a tropical parasitic skin infestation caused by dipterous fly larvae, most commonly affecting travellers to endemic regions. While returning travellers typically present with one or few lesions, extensive parasitism is rare. Increased global mobility and expanding ecological range of myiasis-causing species underscores the need for clinicians in endemic and non-endemic regions to recognise, diagnose, and manage this condition promptly. Awareness of exposure risks—including soil contact, infested clothing, and poor living conditions—is essential to reducing morbidity and preventing complications like secondary bacterial infection. Case Presentation: A healthy male in his forties returned to the UK after a month-long visit to rural Ethiopia, during which he slept on dirt floors and hung his washing on a line. He developed pruritic papular lesions that progressed to erythematous furuncles with central puncta and purulent discharge, accompanied by sensations of movement. The patient self-extracted 12 larvae in Ethiopia and subsequently sought local medical attention, receiving Albendazole, after which emerging larvae were non-motile. On UK presentation, he had 27 lesions at varying stages, 3 with signs of secondary infection. Laboratory investigations revealed elevated inflammatory markers, and wound swabs grew scanty Streptococcus pyogenes. Management included wound occlusion and systemic antibiotics. No further larvae were retrieved, precluding definitive speciation. All lesions improved over subsequent reviews. Conclusions: This case illustrates an unusually extensive presentation of presumed Cordylobia spp. myiasis in a returning traveller, highlighting potential complications following larvicidal therapy. Clinicians should maintain a high index of suspicion for myiasis in patients with compatible cutaneous lesions and relevant history. Increasing travel and shifting vector distributions make familiarity with tropical dermatoses and provision of effective safety measures essential in clinical practice. Full article

Outcomes of influenza virus infection vary widely across individuals, reflecting not only viral genetics and host factors but also the composition and function of the airway microbiome. Over the past few years, mechanistic work has clarified how specific commensals (for example, Staphylococcus epidermidis and Streptococcus oralis) restrict influenza replication by priming epithelial interferon-λ programs, reshaping intracellular metabolite pools (notably polyamines), dampening host protease activity, and maintaining barrier integrity; meanwhile, pathobionts (notably Staphylococcus aureus and Streptococcus pneumoniae) can enhance viral fitness via secreted proteases and neuraminidases that activate hemagglutinin and remodel sialylated glycoconjugates and mucus, setting the stage for secondary bacterial disease. Recent studies also highlight the gut–lung axis: gut microbiota-derived short-chain fatty acids (SCFAs), especially acetate, protect tight junctions and modulate antiviral immunity in influenza models. Together, these insights motivate translational strategies—from intranasal live biotherapeutics (LBPs) to metabolite sprays and decoy/dual neuraminidase approaches—that complement vaccines and antivirals. We synthesize recent evidence and outline a framework for leveraging the airway microbiome to prevent infection, blunt severity, and reduce transmission. Key priorities include strain-level resolution of commensal effects, timing/dosing windows for metabolites and LBPs, and microbiome-aware clinical pathways for anticipating and averting bacterial coinfection. Overall, the airway microbiome emerges as a tractable lever for influenza control at the site of viral entry, with several candidates moving toward clinical testing. Full article

Background and Clinical Significance: Cutaneous aspergillosis caused by Aspergillus flavus is rare and coinfection with Klebsiella pneumoniae was reported only in pulmonary disease. Case Presentation: We describe a 57-year-old woman with no prior comorbidities who developed septic shock requiring intensive care, broad-spectrum antibiotics, corticosteroids, and renal replacement therapy. Six days after discharge, she was readmitted with fever, leukopenia, thrombocytopenia, cavitary lung lesions, and multiple erythematous nodules on the limbs and mammary regions. Bronchial aspirate cultures detected K. pneumoniae, while progressive cutaneous lesions required surgical debridement. Histopathology revealed angioinvasive septate hyphae, and MALDI-TOF identified A. flavus. The K. pneumoniae strain was extensively drug resistant; A. flavus was susceptible only to azoles. Despite targeted therapy, lesions progressed requiring bilateral mastectomy. Conclusions: This case illustrates a previously unreported scenario in which secondary immunosuppression after severe sepsis led to concurrent cutaneous A. flavus infection and extensively drug-resistant (XDR) K. pneumoniae. Early recognition of mixed fungal–bacterial infections is essential for appropriate management. Full article

Hepatic abscesses are uncommon in dogs and typically develop secondary to biliary tract disease or ascending bacterial infections. Although congenital extrahepatic portosystemic shunt (EHPSS) is known to impair hepatic perfusion and immune clearance, its potential role in predisposing geriatric dogs to hepatic abscess formation has not been previously reported. This case report describes the diagnostic approach, therapeutic decision-making, and clinical outcome of a geriatric dog in which a multidrug-resistant hepatic abscess occurred in association with congenital EHPSS, and to propose a pathophysiologic link between chronic portal hypoperfusion and intrahepatic infection. An 11-year-old neutered male Maltese dog with a known EHPSS presented with acute anorexia and lethargy. Diagnostic imaging revealed a hepatic abscess adjacent to the gallbladder, and cytology confirmed a septic process. Despite targeted meropenem therapy based on antimicrobial susceptibility testing, the abscess failed to regress and C-reactive protein levels continued to rise. Concern for persistent biliary contamination and impaired hepatic immune clearance led to surgical intervention. A combined procedure—partial hepatic lobectomy, cholecystectomy, and shunt attenuation—was performed. Postoperative hypotension was managed successfully with vasopressors and transfusion. The patient recovered uneventfully, and at four-month follow-up, hepatic enzyme activities normalized and liver size increased. These findings highlight the need to evaluate hepatic infections in dogs with EHPSS as a potential consequence of impaired hepatic immune clearance rather than an incidental finding. Full article

Background: Urinary tract infections (UTIs) rank among the most prevalent infectious diseases globally, with recurrent UTIs (rUTIs) posing substantial therapeutic challenges due to the lack of durable protective immunity. While trained immunity augments innate immune responses, its induction and functional significance in bladder-resident group 3 innate lymphoid cells (ILC3s) remain unknown. This study investigates whether ILC3s develop trained immunity following uropathogenic Escherichia coli (UPEC) exposure and how they contribute to mucosal defense against rUTIs. Methods: The ILC3 counts were detected in bladder sections from UTI patients and health controls (HC). A recurrent UTI mouse model was established through primary and secondary urethral UPEC inoculation. Bacterial loads in tissues were assessed, and single-cell suspensions were analyzed via flow cytometry. Bladder naïve- and UPEC-trained ILC3s were adoptively transferred, with evaluations of histopathology, epithelial barrier function, inflammation, and antimicrobial peptides. The in vitro ILC3 cell line MNK-3 was detected for IL-17A and IL-22 production following primary and secondary UPEC lysate stimulation. Results: We demonstrate that primary UPEC infection triggers ILC3 expansion in both human and murine bladders. Upon secondary challenge, these ILC3s develop trained immunity, characterized by enhanced proliferation, amplified IL-17A and IL-22 production, and improved pathogen clearance. Mechanistically, trained ILC3s reinforce urothelial barrier integrity through upregulation of antimicrobial peptides (Reg3b/Reg3g) and attenuate inflammatory pathology by suppressing pro-inflammatory cytokines (IL-6, TNF-α). Conclusions: We uncover an endogenous defense mechanism wherein UPEC primes bladder ILC3s via trained immunity, enabling amplified IL-17A- and IL-22-mediated protection against recurrent infections. These findings establish ILC3-trained immunity as a novel conceptual foundation, providing a basis for developing immunotherapies against rUTIs. Full article

Background and Clinical Significance: Henoch–Schönlein purpura (HSP), also known as Immunoglobulin A (IgA) vasculitis (IgAV), is a common systemic vasculitis in children characterized by palpable purpura, abdominal pain, and joint and kidney involvement. While respiratory tract viral or bacterial infections are the most common causes of HSP, parasitic infections, such as giardiasis, are occasionally reported. Giardia lamblia is the most common parasite infecting humans and a major cause of infectious diarrhea, which can lead to post-infection complications. To our knowledge, this is the first report in Greece describing a pediatric patient with HSP secondary to giardiasis. A review of pediatric HSP cases caused by parasitic infections is also included. Case presentation: An 8-year-old girl presented with a purpuric rash, joint tenderness, severe abdominal pain, and bloody diarrhea, raising suspicion of HSP. Laboratory tests revealed elevated IgA levels, and stool analysis tested positive for Giardia lamblia antigen. The diagnosis of HSP secondary to giardiasis was confirmed, and the patient was successfully treated with supportive care, metronidazole, and corticosteroids. Conclusion: This case report and literature review highlight parasitic infections as an underrecognized but important trigger of pediatric HSP. Although giardiasis is linked to various post-infectious complications, its association with HSP is rarely reported. Pediatricians should maintain a high level of suspicion for underlying infectious diarrhea, such as giardiasis, in patients with HSP, especially in children with prominent gastrointestinal symptoms. Early recognition can reduce complications and facilitate faster recovery. Further research is needed for the immunopathogenic mechanisms linking parasitic infections and HSP in children. Full article

Escherichia coli (E. coli) is a ubiquitous opportunistic pathogen in nature and serves as an important reservoir for antibiotic resistance genes. The tet(X4) gene is a key determinant mediating tigecycline resistance. Although its core resistance mechanism, encoding a flavin-dependent monooxygenase, has been elucidated, the broader impact of the tet(X4) gene on the secondary regulatory networks of E. coli remains not fully understood. In recent years, multiple studies have indicated that the tet(X4) gene participates in pathways contributing to resistance to other antibiotics by regulating the expression of various genes. In this study, E. coli tet(X4) gene deletion and complementation strains were constructed to investigate the mechanisms by which the tet(X4) gene influences the growth characteristics and antibiotic resistance of E. coli. The minimum inhibitory concentrations (MICs) of 24 different antibiotics, as well as the degradation capacities of tetracycline and tigecycline, were determined for the wild-type, deletion, and complementation strains. In addition, a four-week starvation stress experiment was performed under both the presence and absence of sub-inhibitory concentrations of tigecycline, during which the bacterial growth curves, survival rates, and MIC variations were analyzed. Transcriptomic sequencing of the wild-type, deletion, and complementation strains identified 531 differentially expressed genes associated with ABC transporter activity, drug metabolism, and bacterial two-component systems. These findings provide reliable evidence for elucidating the mechanism by which the tet(X4) gene affects E. coli resistance, offering valuable insights into the prevention and control of tigecycline-resistant E. coli infections. Full article

Antimicrobial resistance (AMR) is an increasing concern in food animal production. In swine herds, viral infections often lead to secondary bacterial disease and higher antimicrobial use (AMU). This study describes how U.S. swine veterinarians view the role of viral vaccines in reducing this reliance on antimicrobials. We conducted a national survey of swine practitioners and follow-up semi-structured interviews with a subset of respondents. Across participants, porcine reproductive and respiratory syndrome (PRRS), swine influenza (SIV), and rotaviral enteritis were most often named as viral diseases in urgent need of improved vaccines. These diseases cause substantial economic losses and frequently trigger AMU in commercial herds. Veterinarians reported several recurring challenges with current vaccines, including limited cross-protection against field strains, interference from maternally derived antibodies, and short duration of protection. Despite these limitations, most respondents supported vaccination as a key tool to curb AMU and indicated they would accept higher prices for clearly improved products. These findings reveal both a clear need and specific opportunities for future vaccine development to provide broader and more reliable protection, reduce AMU, and help slow the development of AMR. Full article

Background: Cefiderocol (CFD) is a novel cephalosporin targeting multidrug-resistant Gram-negative bacterial (GNB) infections. It mimics siderophores to enter into GNB through iron transport receptors. However, evidence on its use in Hospital at Home (HaH) and outpatient parenteral antibiotic therapy (OPAT) programs remains scarce. Objectives: The primary objective was to evaluate feasibility and efficacy of CFD in HaH setting. The secondary objective was to assess its safety. Methods: A retrospective, observational study was conducted across six Spanish centers between January 2023 and December 2024. Adult patients with documented GNB infections treated with CFD in HaH units were included. Demographic, clinical and microbiological data, treatment characteristics, and outcomes were collected. Statistical analysis was descriptive; no inferential or correlation tests were performed. Results: 27 patients were included; 70.4% were male, with a median age of 69 years. Most infections were nosocomial (65.4%), particularly skin and soft tissue (37%). Septic shock occurred in 14.8% of patients. Pseudomonas aeruginosa (66.7%) and Klebsiella pneumoniae (14.8%) were the most frequent pathogens involved, with Verona Integron-encoded metallo-B-lactamase (VIM, 50%) being the predominant resistance mechanism. CFD was used as a first-line therapy in 63% of cases and in combination with other antibiotics in 40.7%. Median treatment duration was 21.7 days. Administration was mainly via peripherally inserted central catheters (PICC, 33.3%) and electronic pumps (52%). Adverse effects occurred in 7.4% of patients, leading to discontinuation in one case. A total of 88.8% of patients achieved clinical success, with 7.7% recurrence within a month. Escalation of care occurred in 7.7% and 19.2% were readmitted within a month after HaH discharge. No infection-related deaths were reported. Conclusions: CFD is a feasible, safe, and effective treatment for difficult-to-treat GNB infections in HaH settings. Full article

The potyvirus helper component proteinase (HcPro) is a multifunctional protein, with one of its most documented functions being host antiviral RNA silencing suppression. This study shows that the HcPro of potato virus Y (PVY), an important member of the potyvirus group, prevents the replication of a related competing secondary virus. This phenomenon, referred to as superinfection exclusion (SIE), is common in bacterial, human, and plant virus infections. We also report that HcPro’s induction of SIE is strain-specific and that this specificity is provided by the first four amino acid residues of the protein. Consistent with the mechanism of SIE, the study found that HcPro does not exclude a resident virus. Additionally, HcPro’s induction of SIE was observed to function independently of its ability to suppress antiviral RNA silencing. HcPro’s induction of SIE is relevant given the prevalence of multiple PVY strains that routinely co-infect the same cell and that may lead to recombination and emergence of new and more virulent strains. Furthermore, cross-protection or systemic acquired resistance (SAR) that is employed in plant virus disease management occurs when SIE moves from the cellular level and spreads systemically, emphasizing the importance of studying SIE. Full article