Pathogens最新文献

Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Acinetobacter baumannii (CRAB) pose significant therapeutic challenges due to their high resistance and global spread. Combination therapy with colistin (COL) and meropenem (MEM) was used to enhance antimicrobial activity. This study evaluated the COL-MEM combination against CRKP and CRAB isolates with a high resistance profile. A total of 58 carbapenem-resistant clinical isolates (31 CRKP and 27 CRAB), including extensively resistant and pandrug-resistant strains, were collected over a period of 12 months. Synergy between COL and MEM was assessed by microdilution checkerboard (MCB) and time-kill (TKA) assays. Carbapenemase genes were detected using molecular methods. The results showed that the COL-MEM combination yielded synergy (35.5% and 40.7%, respectively) and additive effects (35.5% and 37.0%, respectively), while no antagonism was observed. TKA confirmed bactericidal activity, especially at doubled MCB-detected concentrations, indicating dose-dependent activity. The significant reduction in the minimum inhibitory concentration in the combination indicated its potential for dose optimization, minimizing COL-associated toxicities. Genotypic profiling showed that the expression of bla_NDM and bla_Oxa-48 can reduce synergy. These findings, obtained with isolates of high resistance, support the efficacy of this combination therapy and could reduce the dose-related side effects of COL. However, they also highlight genotype-specific variations and COL resistance mechanisms as limiting variables.

Background: To effectively manage tuberculosis (TB), it is essential to address the high incidence of the disease, as multidrug-resistant pulmonary TB (MDR-PTB) remains a significant concern to halt pre-extensive drug-resistant (pre-XDR) recrudescence. The objective of the current study was to examine and compare MDR-PTB patterns among adult PTB patients (>12 years) in Bangladesh's urban and rural areas who had newly diagnosed and previously treated PTB. Methods: A total of 430 newly diagnosed and previously treated adult patients with PTB were randomly recruited during two study periods: the 1st period, from May 2010 to December 2010 (eight months), and the 2nd period, from January 2014 to January 2015 (thirteen months). Only the drug-resistant (DR) patients were included in the final analysis. Mycobacteriological tests, i.e., smear microscopy, culture, drug susceptibility testing (proportion method of Canetti), line-probe assay, and GeneXpert MTB/RIF were performed. Logistic regression analysis was used to determine the strength of associations between treatment outcomes and predictor variables. Results: Of the newly diagnosed patients, 156 cases were negative and drug-sensitive (DS) at diagnosis, and 274 patients exhibited various DR patterns. During the 1st period, MDR-PTB was 26% among newly diagnosed patients, while the proportion was 31% among previously treated patients in the 2nd period. The majority of MDR-PTB belonged to the age group of ≤45 years. Male patients consistently revealed a higher proportion of MDR-PTB compared to females in both the newly diagnosed and previously treated groups. Conclusion: The proportion of MDR-PTB was higher among the previously treated patients than among newly diagnosed patients. Regardless of demographic characteristics, a significant proportion of patients showed DR, particularly in previously treated groups, indicating a substantial burden of MDR-PTB.

Tick-borne diseases account for a substantial proportion of the global incidence of infectious diseases, and their recent expansion has been increasingly associated with climate change. Nevertheless, previous studies have produced heterogeneous and often inconclusive results, largely due to differences in spatial scale, variable selection, and limited integration of climatic, ecological, and host-related drivers. Here, we assess the modeled impact of climate trends on the global distribution patterns of ticks parasitizing humans and livestock, rather than changes in tick abundance or pathogen transmission. This study is not an evaluation of human or animal contact rates with ticks. Using the largest curated compilation of georeferenced tick records available to date (213,513 records from 138 Ixodidae species), we adopt a global, climate-centered perspective based on the Holdridge life zones framework. The study characterized current climatic niches of tick genera and projected changes in suitability under future climate scenarios for 2040, 2060, 2080, and 2100. Our results reveal a strong association between tick occurrence patterns and large-scale gradients of temperature and atmospheric water balance, while precipitation plays a comparatively minor role. Projections indicate increasing climatic suitability for human-biting ticks at higher northern latitudes, concurrent with declining suitability across parts of central and southern Africa. By integrating modeled suitability with human population projections and livestock distributions, we estimated future changes in exposure risk. Although local processes such as tick abundance and pathogen prevalence are beyond the scope of this study, our findings provide a coherent global synthesis of how climate change may reshape tick distributions and associated risks.

Hepatitis E virus (HEV) is a global public health concern, causing over 20 million infections annually. It is primarily transmitted via the fecal-oral route, with wild boars and domestic swine as major reservoirs involved in zoonotic transmission. Bahía de Samborombón is an important natural reserve in Argentina characterized by a high population of wild boars, located in a livestock-intensive region near major urban centers. As part of a wild boar control program, 11 sampling campaigns were carried out between 2022 and 2023. Fecal, blood, and liver samples were systematically collected from 80 captured animals for the detection and characterization of HEV through antibody and RNA testing. Serological analysis revealed a positivity rate of 42.4%, whereas RT-qPCR detected HEV RNA in 9.1% of fecal samples and 12.5% of liver samples. From the positive samples, seven viral sequences were recovered using RT-nested PCR, including six from ORF1 and one from ORF2. Phylogenetic analysis clustered these sequences within zoonotic HEV genotype 3, showing a close relationship with human sequences from Buenos Aires and neighboring provinces. This study confirms the presence of HEV in wild boars from Argentina, highlighting the circulation of genotype 3, clade abchijklmno and the associated zoonotic risk.

Oral squamous cell carcinoma (OSCC) accounts for the majority of feline oral neoplasms and carries a poor prognosis; however, the oral microbiome in affected cats remains poorly characterized. This study aimed to preliminarily describe the oral bacterial communities of cats with OSCC and compare them with those of clinically healthy cats using DNA amplicon sequencing. Oral swabs were collected from cats with OSCC, including tumor surfaces, tumor cut surfaces, and clinically normal mucosa distant from the tumor (n = 20 total samples), and from the gingival margin of healthy cats (n = 12). DNA was extracted and full-length 16S rRNA gene sequencing was performed to assess microbial composition and diversity. Cats with OSCC exhibited significant alterations in oral microbiota compared with healthy controls, including reduced alpha diversity, distinct beta-diversity clustering, and consistent taxonomic shifts. Healthy cats displayed a relatively conserved core microbiome dominated by Porphyromonas spp., Bacteroides, Pasteurellaceae, Helcococcus, and Moraxella. In contrast, OSCC-associated samples showed increased relative abundances of anaerobic and disease-associated taxa, including Filifactor villosus, Bacteroides pyogenes, Odoribacter denticanis, Porphyromonas circumdentaria, and members of the Pasteurellaceae. These findings provide the first description of the oral microbiota associated with feline OSCC and demonstrate exploratory microbial differences between health and disease.

Highly pathogenic avian influenza (HPAI) A/H5N1 has emerged as a cause of severe disease in domestic cats, but clinical data from field outbreaks remain limited. We retrospectively reviewed medical records, laboratory results, and ancillary examinations from 22 domestic cats with RT-qPCR-confirmed A/H5N1 infection diagnosed in Poland in June 2023. To the best of our knowledge, we report the first comprehensive retrospective case series from the 2023 Polish outbreak, combining 22 laboratory-confirmed cats with detailed clinical timelines and laboratory findings. For each cat, the temporal progression of clinical signs, hematology, serum biochemistry, and, when available, imaging findings were evaluated. Post-mortem examination data were not systematically available in this retrospective cohort. Notably, six of these cats were strictly indoor cats that received raw poultry meat as part of their diet. Disease onset was acute, with fever, lethargy, and anorexia rapidly progressing to severe dyspnea and neurological signs, including ataxia, seizures, and paraplegia; case fatality was 100%, with a typical interval of ≤3 days from first signs to death or euthanasia. Hematologic changes were dominated by thrombocytopenia, lymphopenia, and marked eosinopenia, consistent with a systemic inflammatory/stress leukogram. Biochemistry indicated marked tissue injury, with increased AST, LDH, and CK activities, whereas creatinine and urea remained largely within reference intervals, arguing against primary renal failure. Imaging supported the presence of interstitial to diffuse pneumonia. These data characterize the clinical and laboratory phenotypes of feline A/H5N1 infection and underscore its importance as a rapidly fatal respiratory and neurological disease with One Health implications.

Understanding the intrinsic potential of persistent dengue virus (DENV) replication and survival in vector host cells is critically important. In this study, we investigated to what extent DENV can replicate within the vector host Aedes albopictus C6/36 mosquito cells (cell line routinely used for propagation of DENV in research laboratories). We detected DENV serotype 2 (DENV2) loads in cell culture supernatants collected at different days post infection (3, 19, 33, 60, 90, 120 and 175) and found the presence of capsid transcripts and protein levels in these virus supernatants. Tissue culture infectious dose 50 (TCID50) assay revealed a gradual reduction in viral titers and infectivity from days 19 to 175 post DENV2 infection. Furthermore, infection kinetics with these virus supernatants collected at different days post DENV2 infection demonstrated declining viral replication in naïve C6/36 cells and human endothelial recipient cells. These results provided information on viral replication competence and the persistency of DENV2 infection from days 19 to 175 in mosquito cells. Extracellular vesicles (EVs) isolated from DENV2-infected C6/36 cell culture supernatants showed a progressive increase in EV concentration from day 33 to day 175. While DENV2 loads within these EVs declined over time, their ability to mediate infection in naïve C6/36 and endothelial cells remained constant. Notably, the viral membrane (M) protein was detected in EVs at days 3, 19, and 33 but was absent at later timepoints (days 60, 90, 120, and 175). The prM protein was not detected in any of the samples analyzed. In conclusion, DENV2 exhibits the capacity for persistent infection in mosquito cells, thereby potentially serving as a model for investigating the mechanisms that govern years of long-term and sustained viral infections within the vector host.

Pyrrolomycins and marinopyrroles are natural products originally derived from Streptomyces spp. that possess potent anti-infective activity against a variety of organisms, including drug-resistant bacteria and eukaryotic pathogens, especially pertinent amid the search for additional antimicrobial agents. These highly halogenated compounds have been proposed to act as protonophores, an uncommon mechanism of action that likely contributes to their broad-spectrum antibacterial activity. To improve efficacy and overcome limitations to clinical transition, promising derivatives of these natural compounds have been synthesized, introducing structural refinements that enhance pharmacological properties while preserving potent anti-infective activity. Recent discoveries demonstrate the potential of pyrrolomycins and marinopyrroles derivatives to serve as broad-spectrum anti-infective agents with efficacy against drug-resistant bacteria, bacterial biofilms, parasitic infections, and some viruses.

Bone infections, including osteomyelitis, prosthetic joint infections, and fracture-related infections, represent a persistent and growing clinical problem associated with substantial morbidity, mortality, and healthcare costs. Their management is complicated by limited bone vascularization, biofilm formation, intracellular bacterial persistence, dysregulated host immune responses and reduced antibiotic delivery to the infection site, which promote chronic infection and recurrence. The limitations of conventional treatment strategies based on surgical debridement and prolonged systemic antibiotic therapy, together with their association with antimicrobial resistance and systemic toxicity, have led to growing interest in alternative and adjunctive therapeutic approaches. Local antibiotic delivery systems, such as polymethyl methacrylate, calcium sulfate, hydroxyapatite-based composites, hydrogels, antibiotic-impregnated bone grafts, and nanoparticle carriers, enable high local antimicrobial concentrations while minimizing systemic exposure. From a different therapeutic perspective, immunomodulatory strategies, including mesenchymal stem cell-based therapies, cytokine-targeted interventions, bacteriophages, quorum-sensing inhibitors, and non-antibiotic antimicrobials, represent emerging approaches aimed at improving infection control and supporting bone regeneration. Advances in biomarker profiling, molecular diagnostics, and artificial intelligence-assisted analyses further support personalized approaches to diagnosis, monitoring, and treatment. Despite encouraging early results, clinical translation remains limited by methodological and regulatory challenges, underscoring the need for integrated, innovative treatment strategies.

Salmonella Infantis is a recognized antimicrobial resistance threat, and in the compromised chicken gut, this pathogen penetrates weakened tight junctions, disrupts the microbiota balance, and triggers inflammation. This study evaluated the potential effects of a feed additive blend comprising short chain fatty acids including coated sodium and calcium butyrate, medium chain fatty acids, and phenolic compounds on broiler gut health and performance under a Salmonella challenge using a proprietary seeder model methodology. The foundation, led by a preliminary study as Part A, comprises a negative control and two treatment groups, ran to develop a seeder model, and 1056 day-old Ross 308 broiler chicks were allocated into three groups. On days 5-6, Salmonella Infantis 7570 was inducted via seeders in T2 (frozen strain) and T3 (live strain), while T1 remained unchallenged. No significant difference in infection development was observed between T2 and T3 (p > 0.05). In T1, Salmonella positivity checked via real time polymerase chain reaction (iQ-check II Biorad) remained below 50% at respective time points, indicating that complete isolation in the same room is not feasible. Henceforth, in the main experiment, Part B, 396 male day-old Ross 308 birds were randomly assigned to two further treatments: (1) a positive control group fed a commercial diet, and (2) a treatment group fed the same diet supplemented with 2.5 kg/t of an organic acid-based additive blend (Presan FY, Tilburg, The Netherlands) until day 28. On days 5 and 6, five birds per pen were orally inoculated with 10⁹ CFU/mL Salmonella Infantis 7570 obtained via Part A and placed as seeders in both treatments. A borderline tendency for lower Salmonella counts was observed in the treatment group on day 19 (p = 0.062). The control group had significantly higher lesion scores on day 13 (p = 0.0068), with no significant difference on day 19. Body weight was significantly higher in the treatment group on days 11 and 28 (p = 0.0157), with no difference on day 39 (p = 0.1857). Average daily gain improved significantly between days 11 and 28 (p = 0.0234), and feed intake was also significantly higher during this period (p = 0.0007). Feed conversion ratio showed a tendency to improve between days 5 and 11 (p = 0.0638). Overall, this study reveals that the seeder model can be adopted in Salmonella research, and the application of a blend showed a borderline tendency to reduce Salmonella counts, however significantly lower the lesion scores, thereby improving gut health in broilers under a Salmonella challenge.