Search Results (2,559)

Phage therapy, long overshadowed by antibiotics in Western medicine, has a well-established history in some Eastern European countries and is now being revitalized as a promising strategy against antimicrobial resistance (AMR). This resurgence of phage therapy is driven by the urgent need for innovative countermeasures to AMR, which will cause an estimated 10 million deaths annually by 2050. However, the emergence of phage-resistant variants presents challenges similar to AMR, thus necessitating a deeper understanding of phage resistance mechanisms and control strategies. The highest priority must be to prevent the emergence of phage resistance. Although phage cocktails targeting multiple receptors have demonstrated a certain level of phage resistance suppression, they cannot completely suppress resistance in clinical settings. This highlights the need for strategies beyond simple resistance suppression. Notably, recent studies examining fitness trade-offs associated with phage resistance have opened new avenues in phage therapy that offer the potential of restoring antibiotic susceptibility and attenuating pathogen virulence despite phage resistance. Thus, controlling phage resistance may rely on both its suppression and strategic redirection. This review summarizes key concepts in the control of phage resistance and explores evolutionary engineering as a means of optimizing phage therapy, with a particular focus on Pseudomonas infections. Harnessing evolutionary dynamics by intentionally breaking the spontaneous evolutionary trajectories of target bacterial pathogens could potentially reshape bacterial adaptation by acquisition of phage resistance, unlocking potential in the application of phage therapy. Full article

This article analyzes the work of Fr. Elias Friedman, whose legacy of theological work on Jewish identity and Jewish conversion to Catholicism serves as the foundation of the Association of Hebrew Catholics, of which he is the founder. Friedman frames his work as a sensitive approach to Jewish identity and Catholic faith, but as this paper demonstrates, his work reveals a reiteration of some of the most entrenched and historically devastating tropes of Christian anti-Judaism, as well as racial antisemitism. This article presents three main arguments. First, it demonstrates that Friedman’s work evidences a theological anti-Judaism characteristic of Catholicism prior to the Second Vatican Council, which he maintained firmly even after the theological revision of Vatican II rejected such views; and furthermore, that his work also expresses an antisemitism that reflects the modern racial antisemitism adopted by the Nazi regime. Second, this article examines the positive reception of Friedman’s work, as evidenced not only in the revered position he holds within the Association for Hebrew Catholics, but also by the nihil obstat and imprimatur on both of Friedman’s monographs, that is, the official stamp of ecclesiastical approval within the Catholic Church, which declares that the work is “free of doctrinal and moral error.” It proposes that these factors evidence the uncritical reception of his work not only within the Association of Hebrew Catholics, but also on behalf of the institutional Catholic Church. Third, it raises the question of the extent to which Friedman’s identity as a Jewish convert to Catholicism is relevant in the analysis and reception of his work. It argues that his Jewish identity makes his concoction of religious anti-Judaism and racial antisemitism particularly potent, rendering anodyne even the most virulently antisemitic of his statements. Full article

Streptococcus pyogenes (GAS) is a leading cause of acute otitis media (AOM) and its complications. This study aimed to evaluate the antimicrobial resistance of all isolated bacterial agents recovered from children with AOM and to perform the emm typing of GAS isolates. Antibiotic susceptibility testing was evaluated according to EUCAST criteria. Phenotyping and genotyping were performed for the macrolide-resistant GAS isolates. All GAS isolates were subjected to emm typing. Among the 103 AOM cases considered, we identified GAS isolates (39.4%), Staphylococcus aureus (26.6%), Haemophilus influenzae (13.8%), Streptococcus pneumoniae (11.7%), Moraxella catarrhalis (7.4%), and Serratia marcescens (1.1%). GAS exhibited 32.4% macrolide resistance and 10.8% clindamycin resistance. The M phenotype and mefE gene (18.9%) were the most common, followed by cMLSB (10.8% with ermB), a combination of mefA and ermB (8.1%), and iMLSB (2.7% with ermA). The most prevalent emm types were emm12 (27.0%), emm1 (21.6%), and emm3 (16.2%). The most common GAS emm types identified among AOM patients in this study are found worldwide and are associated with invasive infections in various countries. This may influence the virulence and invasive potential of these strains. Full article

Streptococcus iniae (S. iniae) is a globally significant aquatic pathogen responsible for severe economic losses in aquaculture. While the S. iniae infection often exhibits distinct seasonal patterns strongly correlated with water temperature, there is limited knowledge regarding the temperature-dependent immune evasion strategies of S. iniae. Our results demonstrated a striking temperature-dependent virulence phenotype, with significantly higher A. latus mortality rates observed at high temperature (HT, 33 °C) compared to low temperature (LT, 23 °C). Proteomic analysis revealed temperature-dependent upregulation of key virulence factors, including streptolysin S-related proteins (SagG, SagH), antioxidant-related proteins (SodA), and multiple capsular polysaccharide (cps) synthesis proteins (cpsD, cpsH, cpsL, cpsY). Flow cytometry analysis showed that HT infection significantly reduced the percentage of lymphocyte and myeloid cell populations in the head kidney leukocytes of A. latus, which was associated with elevated caspase-3/7 expression and increased apoptosis. In addition, HT infection significantly inhibited the release of reactive oxygen species (ROS) but not nitric oxide (NO) production. Using S. iniae cps-deficient mutant, Δcps, we demonstrated that the cps is essential for temperature-dependent phagocytosis resistance in S. iniae, as phagocytic activity against Δcps remained unchanged across temperatures, while NS-1 showed significantly reduced uptake at HT. These findings provide new insights into the immune evasion of S. iniae under thermal regulation, deepening our understanding of the thermal adaptation of aquatic bacterial pathogens. Full article

Proteus mirabilis is a zoonotic pathogen that poses a growing threat to both animal and human health due to rising antimicrobial resistance (AMR). It is widely found in animals, including China’s nationally protected captive giant and red pandas. This study isolated Proteus mirabilis from panda feces to assess AMR and virulence traits, and used whole-genome sequencing (WGS) to evaluate the spread of resistance genes (ARGs) and virulence genes (VAGs). In this study, 37 isolates were obtained, 20 from red pandas and 17 from giant pandas. Multidrug-resistant (MDR) strains were present in both hosts. Giant panda isolates showed the highest resistance to ampicillin and cefazolin (58.8%), while red panda isolates were most resistant to trimethoprim/sulfamethoxazole (65%) and imipenem (55%). Giant panda-derived strains also exhibited stronger biofilm formation and swarming motility. WGS identified 31 ARGs and 73 VAGs, many linked to mobile genetic elements (MGEs) such as plasmids, integrons, and ICEs. In addition, we found frequent co-localization of drug resistance genes/VAGs with MGEs, indicating a high possibility of horizontal gene transfer (HGT). This study provides crucial insights into AMR and virulence risks in P. mirabilis from captive pandas, supporting targeted surveillance and control strategies. Full article

Objectives: Burkholderia cepacia complex (Bcc), a Gram-negative organism, is a well-recognized cause of hospital outbreaks, often linked to a contaminated shared source, such as multidose medications. In this study, we report an outbreak of Bcc infections in a tertiary care hospital, associated with the intrinsic contamination of a prepared solution used in interventional radiology (IR) procedures. Additionally, we provide a detailed explanation of the interventions implemented to control and interrupt the outbreak. Methods: Records from the infection control committee from 1 January 2023 to 31 October 2024 were screened to identify cases with Bcc growth in cultured blood, urine, or respiratory samples. Clinical and laboratory data were collected in March 2025. Bacterial identification was performed using conventional methods and MALDI-TOF (Bruker Daltonics, Bremen, Germany). Controls were matched to cases by ward, date of initial growth, and duration of hospitalization. Demographic and clinical data of these patients were systematically collected and analyzed. Microbiological cultures were obtained from environmental objects of concern and certain medications. Results: A total of 82 Burkholderia species were identified. We enrolled 77 cases and 77 matched controls. The source of contamination was identified in ready-to-use intravenous medications (remifentanil and magnesium preparations) in the IR department. These preparations were compounded in advance by the team and were used repeatedly. Although the outbreak originated from contaminated IV medications used in IR, secondary transmission likely affected 28 non-IR patients via fomites, shared environments, and possible lapses in isolation precautions. The mortality rate among the cases was 16.9%. Infection with Bcc was associated with prolonged intensive care unit stays (p = 0.018) and an extended overall hospitalization duration (p < 0.001); however, it was not associated with increased mortality. The enforcement of contact precautions and comprehensive environmental decontamination successfully reduced the incidence of the Bcc outbreak. No pathogens were detected in cultures obtained after the disinfection. Conclusions: The hospital transmission of Bcc is likely driven by cross-contamination, invasive medical procedures, and the administration of contaminated medications. Implementing stringent infection control measures such as staff retraining, updated policies on medication use, enhanced environmental decontamination, and strict adherence to isolation precautions has proven effective in curbing the spread of virulent and transmissible Bcc. Full article

Background: The spread of ESBL-producing Enterobacteriaceae (ESBL-PE) strains in food poses a potential risk to human health. The aim of the study was to determine the occurrence of ESBL-PE and to investigate their distribution on foods. Methods: A total of 1000 food samples, including both raw and ready-to-eat products, was analyzed for the presence of ESBL-producing Enterobacteriaceae using chromogenic selective agar. Antibiotic resistance in the isolated strains was assessed using conventional methods, while whole-genome sequencing was employed to predict antimicrobial resistance and virulence genes. Results: The overall occurrence of ESBL-PE strains was 2.8%, with the highest contamination in raw meat samples (10%). A total of 31 multidrug-resistant (MDR) strains was isolated, mainly Escherichia coli, followed by Klebsiella pneumoniae, Salmonella enterica, and Enterobacter hormaechei. All strains exhibited high levels of resistance to at least four different β-lactam antibiotics, as well as to other antimicrobial classes including sulfonamides, tetracyclines, aminoglycosides, and quinolones. Whole-genome sequencing identified 63 antimicrobial resistance genes, with bla_CTX-M being the most prevalent ESBL gene. Twenty-eight (90%) isolates carried Inc plasmids, known vectors of multiple antimicrobial resistance genes, including those associated with ESBLs. Furthermore, several virulence genes were identified. Conclusions: The contamination of food with ESBL-PE represents a potential public health risk, underscoring the importance of the implementation of genomic surveillance to monitor and control the spread of antimicrobial resistance. Full article

Penicillium astrolabium is a primary pathogenic fungus that causes grape blue mold during postharvest, leading to substantial losses in the grape industry. Nevertheless, hypovirulence-associated mycoviruses can attenuate the virulence of postharvest grape-rot pathogens, thereby offering a promising biocontrol tool. Characterizing the mycovirus repertoire of P. astrolabium is imperative for grape protection, yet remains largely unexplored. Here, we screened six strains harboring viruses in 13 P. astrolabium isolates from rotted grapes. Using high-throughput sequencing, four novel dsRNA viruses and two +ssRNA viruses were identified from the six P. astrolabium strains. The dsRNA viruses belonged to two families—Chrysoviridae and Partitiviridae—and were designated to Penicillium astrolabium chrysovirus 1 (PaCV1), Penicillum astrolabium partitivirus 1′ (PaPV1′), Penicillum astrolabium partitivirus 2 (PaPV2), and Penicillum astrolabium partitivirus 3 (PaPV3). For the +ssRNA viruses, one was clustered into the Alphaflexiviridae family, while the other one was clustered into the Narnaviridae family. The two +ssRNA viruses were named Penicillium astrolabium alphaflexivirus 1 (PaAFV1) and Penicillium astrolabium narnavirus 1 (PaNV1), respectively. Moreover, several viral genomic contigs with non-overlapping and discontinuous sequences were identified in this study, which were probably representatives of five viruses from four families, including Discoviridae, Peribunyaviridae, Botourmiaviridae, and Picobirnaviridae. Taken together, our findings could expand the diversity of mycoviruses, advance the understanding of mycovirus evolution in P. astrolabium, and provide both potential biocontrol resources and a research system for dissecting virus–fungus–plant interactions. Full article

Monkeypox virus (MPXV) has caused 148,892 confirmed cases and 341 deaths from 137 countries worldwide, as reported by the World Health Organization (WHO), highlighting the urgent need for effective vaccines to prevent the spread of MPXV. Traditional vaccine development is low-throughput, expensive, time consuming, and susceptible to reversion to virulence. Alternatively, a reverse vaccinology approach offers a rapid, efficient, and safer alternative for MPXV vaccine design. Here, MPXV proteins associated with viral infection were analyzed for immunogenic epitopes to design multi-epitope vaccines based on B-cell, CD4+, and CD8+ epitopes. Epitopes were selected based on allergenicity, antigenicity, and toxicity parameters. The prioritized epitopes were then combined via peptide linkers and N-terminally fused to various protein adjuvants, including PADRE, beta-defensin 3, 50S ribosomal protein L7/12, RS-09, and the cholera toxin B subunit (CTB). All vaccine constructs were computationally validated for physicochemical properties, antigenicity, allergenicity, safety, solubility, and structural stability. The three-dimensional structure of the selected construct was also predicted. Moreover, molecular docking and molecular dynamics (MD) simulations between the vaccine and the TLR-4 immune receptor demonstrated a strong and stable interaction. The vaccine construct was codon-optimized for high expression in the E. coli and was finally cloned in silico into the pET21a (+) vector. Collectively, these results could represent innovative tools for vaccine formulation against MPXV and be transformative for other infectious diseases. Full article

Background/Objectives: Among Enterobacterales, OXA-48-like-producing Proteus mirabilis strains have been scarcely detected. Herein, we characterized a bla_OXA-48-harbouring P. mirabilis strain recovered from Greece (Pm GR-1), while phylogenomics and comparative genomics analyses with previously published bla_OXA-48 carriers were also assessed. Methods: Characterization of Pm GR-1 was performed by the Vitek^® Compact and Mass Spectrometry systems, antimicrobial susceptibility testing, detection of beta-lactamases, multilocus-sequence typing (MLST), and whole-genome sequencing (WGS). In silico prediction of mobile genetic elements (MGEs), genomic islands (GIs), antimicrobial resistance genes (ARGs) and virulence factors (VFs), and phylogenetic, core-genome SNP and comparative genomics analyses were executed using bioinformatic tools. Results: Pm GR-1 was isolated from a urine sample of an outpatient in a Greek hospital. It exhibited a multidrug-resistant phenotype, being susceptible only to amikacin and ceftazidime/avibactam. It co-carried several beta-lactamase genes on the chromosome (bla_OXA-48, bla_CTX-M-14, bla_TEM-1) and a plasmid (bla_TEM-2) and several other ARGs, but also mutations associated with quinolone resistance in the DNA gyrase and topoisomerase IV subunits. It belonged to the international clone ST135 that has also been detected among OXA-48-producing P. mirabilis strains from Germany and the USA. Pm GR-1 was genetically related to those from Germany, sharing highly similar MGEs, GIs, ARGs and VFs, including the chromosomal bla_OXA-48 genetic structure, the O-antigen locus, the flagella locus, the MR/P fimbriae operon, and the urease gene cluster. Conclusions: To our knowledge, this is the first report from Greece of a bla_OXA-48-possessing P. mirabilis strain. The emergence of bla_OXA-48 among P. mirabilis strains of the international clone ST135 in different geographical regions is worrying. Close monitoring of these strains is required in One Health settings. Full article

Background: Chryseobacterium indologenes, an environmental bacterium, is increasingly recognized as an emerging nosocomial pathogen, particularly in Asia, and is often characterized by multidrug resistance. Objectives: This study aimed to investigate the genomic features of clinical C. indologenes isolates from Maharaj Nakorn Chiang Mai Hospital, Thailand, to understand their mechanisms of multidrug resistance, virulence factors, and mobile genetic elements (MGEs). Methods: Twelve C. indologenes isolates were identified, and their antibiotic susceptibility profiles were determined. Whole genome sequencing (WGS) was performed using a hybrid approach combining Illumina short-reads and Oxford Nanopore long-reads to generate complete bacterial genomes. The hybrid assembled genomes were subsequently analyzed to detect antimicrobial resistance (AMR) genes, virulence factors, and MGEs. Results: C. indologenes isolates were primarily recovered from urine samples of hospitalized elderly male patients with underlying conditions. These isolates generally exhibited extensive drug resistance, which was subsequently explored and correlated with genomic determinants. With one exception, CMCI13 showed a lower resistance profile (Multidrug resistance, MDR). Genomic analysis revealed isolates with genome sizes of 4.83–5.00 Mb and GC content of 37.15–37.35%. Genomic characterization identified conserved resistance genes (bla_IND-2, bla_CIA-4, adeF, vanT, and qacG) and various virulence factors. Phylogenetic and pangenome analysis showed 11 isolates clustering closely with Chinese strain 3125, while one isolate (CMCI13) formed a distinct branch. Importantly, each isolate, except CMCI13, harbored a large genomic island (approximately 94–100 kb) carrying significant resistance genes (bla_OXA-347, tetX, aadS, and ermF). The absence of this genomic island in CMCI13 correlated with its less resistant phenotype. No plasmids, integrons, or CRISPR-Cas systems were detected in any isolate. Conclusions: This study highlights the alarming emergence of multidrug-resistant C. indologenes in a hospital setting in Thailand. The genomic insights into specific resistance mechanisms, virulence factors, and potential horizontal gene transfer (HGT) events, particularly the association of a large genomic island with the XDR phenotype, underscore the critical need for continuous genomic surveillance to monitor transmission patterns and develop effective treatment strategies for this emerging pathogen. Full article

Acinetobacter baumannii has emerged as a major pathogen responsible for healthcare-associated infections, particularly in intensive care units, contributing to significant morbidity and mortality due to its multidrug resistance and ability to persist in clinical environments. This study aimed to investigate the phenotypic and genomic characteristics of all multidrug-resistant A. baumannii isolates collected between January and June 2022 from two tertiary care hospitals in Thessaloniki, Greece. A total of 40 isolates were included. All isolates exhibited resistance to colistin; however, none harbored the mcr-1 to mcr-9 genes, as confirmed by polymerase chain reaction (PCR). PCR-based screening for virulence-associated genes revealed high prevalence rates of basD (100%), pld (95%), csuE (87.5%), and bap (77.5%). In contrast, ompA and pglC were not detected. Twitching motility ranged from 2 to 50 mm, with 25% of the isolates classified as non-motile and 20% as highly motile. Swarming motility was observed in all strains. Additionally, all isolates demonstrated positive α-hemolysis, suggesting a potential virulence mechanism involving tissue damage and iron acquisition. Pulsed-field gel electrophoresis (PFGE) revealed significant genomic diversity among the isolates, indicating a low likelihood of patient-to-patient or clonal transmission within the hospital setting. These findings highlight the complex relationship between antimicrobial resistance and virulence in clinical A. baumannii isolates and emphasize the urgent need for robust infection control strategies and continued microbiological surveillance. Full article

The role of Enterococcus spp. in food is debated since this group of lactic acid bacteria contains opportunistic pathogenic strains, some of which exhibit a multidrug-resistant profile. In livestock farms, the use of antibiotics is the most common practice to deal with mastitis-causing bacteria. However, the heavy usage and/or misuse of antibiotics has led to the emergence of antibiotic resistance. This study aimed to genetically and phenotypically characterize Enterococcus strains isolated from raw sheep milk. Samples were collected over one year from the bulk tank of a dairy sheep farm and cultured on selective media. Isolates were purified and analyzed by whole-genome sequencing and antimicrobial susceptibility testing. The isolates were divided into clusters and the corresponding species were identified along with their genes related to virulence and antibiotic resistance. The pan-, core- and accessory-genomes of the strains were determined. Finally, the antibiotic-resistant profile of selected strains was examined and associated with their genomic characterization. These findings contribute to a better understanding of Enterococci epidemiology, providing comprehensive profiles of their virulence and resistance genes. The presence of antibiotic-resistant bacteria in raw sheep milk destined for the production of cheese should raise awareness. Full article

Listeria monocytogenes is a life-threatening bacterial foodborne pathogen that can persist in food-processing facilities for years. Although phages can control L. monocytogenes during food production, phage-resistant bacterial subpopulations can regrow in phage-treated environments. In this study, an L. monocytogenes hly defective strain, NJ05-Δhly, was produced, which considerably regulated the interactions between L. monocytogenes and phages. Specifically, we observed a 76.92-fold decrease in the efficiency of plating of the defective strain following infection with the Listeria phage vB-LmoM-NJ05. The lytic effect was notably diminished at multiplicities of infection of 1 and 10. Furthermore, the inactivation of LLO impaired biofilm formation, which was completely suppressed and eliminated following treatment with 10⁸ PFU/mL of phage. Additionally, phages protected cells from mitochondrial membrane damage and the accumulation of mitochondrial reactive oxygen species induced by L. monocytogenes invasion. Transcriptomic analysis confirmed these findings, revealing the significant downregulation of genes associated with phage sensitivity, pathogenicity, biofilm formation, and motility in L. monocytogenes. These results underscore the vital role of LLO in regulating the pathogenicity, phage susceptibility, and biofilm formation of L. monocytogenes. These observations highlight the important role of virulence factors in phage applications and provide insights into the potential use of phages for developing biosanitizers. Full article

Background: Antibiotics at sub-inhibitory concentrations can rewire bacterial regulatory networks, impacting virulence. Objective: The way that exposure to selected antibiotics (ciprofloxacin, amikacin, azithromycin, ceftazidime, and meropenem) below their minimum inhibitory concentration (sub-MIC) modulates the physiology of Pseudomonas aeruginosa is examined in this study using growth-phase-resolved analysis. Methods: Standard P. aeruginosa strain cultures were exposed to ¼ and ½ MIC to determine the growth kinetics under antibiotic stress. The study measured protease and pyocyanin production and the expression level of important quorum sensing and virulence genes (lasI/R, rhlI/R, pqsR/A, and phzA) at different growth phases. Results: Meropenem produced the most noticeable growth suppression at ½ MIC. Sub-MIC antibiotics did not completely stop growth, but caused distinct, dose-dependent changes. Azithromycin eliminated protease activity in all phases and had a biphasic effect on pyocyanin. Ciprofloxacin consistently inhibited both pyocyanin and protease in all phases. The effects of amikacin varied by phase and dose, while β-lactams markedly increased pyocyanin production during the log phase. In contrast to the plateau phase, when expression was often downregulated or unchanged, most quorum-sensing- and virulence-associated genes showed significant upregulation during the death phase under sub-MIC exposure. Conclusions: These findings indicate that sub-MIC antibiotics act as biochemical signal modulators, preserving stress-adapted sub-populations that, in late growth phases, activate quorum sensing and stress tolerance pathways. Full article