Search Results (713)

Biofilms are a spontaneously formed slimy matrix of extracellular polymeric substances (EPS) enveloping miniature bacterial colonies, which aid in pathogen colonization, shielding the bacteria from antibiotics, as well as imparting them resistance towards the same. Biofilms employ a robust communication mechanism called quorum sensing that serves to keep their population density constant. What is most significant about biofilms is that they contribute to the development of bacterial virulence by providing protection to pathogenic species, allowing them to colonize the host, and also inhibiting the activities of antimicrobials on them. They grow on animate surfaces (such as on teeth and intestinal mucosa, etc.) and inanimate objects (like catheters, contact lenses, pacemakers, endotracheal devices, intrauterine devices, and stents, etc.) alike. It has been reported that as much as 80% of human infections involve biofilms. Serious implications of biofilms include the necessity of greater concentrations of antibiotics to treat common human infections, even contributing to antimicrobial resistance (AMR), since bacteria embedded within biofilms are protected from the action of potential antibiotics. This review explores various contemporary strategies for controlling biofilms, focusing on their modes of action, mechanisms of drug resistance, and innovative approaches to find a solution in this regard. This review interestingly targets the extracellular polymeric matrix as a highly effective strategy to counteract the potential harm of biofilms since it plays a critical role in biofilm formation and significantly contributes to antimicrobial resistance. 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

Listeria monocytogenes poses health threats due to its resilience and potential to cause severe infections, especially in vulnerable populations. Plant extracts and/or phytocomplexes have demonstrated the capability of natural compounds in mitigating L. monocytogenes virulence. Here we explored the suitability of a computational pipeline envisioned to identify the molecular determinants for the recognition between the bacterial protein internalin A (InlA) and the human E-cadherin (Ecad), which is the first step leading to internalization. This pipeline consists of molecular docking and extended atomistic molecular dynamics simulations to identify key interaction clusters between InlA and Ecad. It exploits this information in the screening of chemical libraries of natural compounds that might competitively interact with InIA and hence impede the formation of the InIA–Ecad complex. This strategy was effective in providing a molecular model for the anti-adhesive activity of punicalagin and disclosed two natural phenolic compounds with a similar interaction pattern. Besides elucidating key aspects of the mutual recognition between InIA and Ecad, this study provides a molecular basis about the mechanistic underpinnings of the anti-adhesive action of punicalagin that enable application against L. monocytogenes. Full article

In this paper, we present a mathematical model, $M_{siqr}$, to analyze the dynamics of mobile malware propagation in smartphone networks. The model segments the mobile device population into susceptible, exposed, infected, quarantined, and recovered compartments, integrating critical control parameters such as infection and quarantine rates. The analytical results include the derivation of the basic reproduction number, $R_0$, along with equilibrium and stability analyses that provide insights into long-term system behavior. A focused scenario analysis compares the baseline dynamics with a more aggressive malware variant and a more effective quarantine response. The results show that increased infectivity sharply escalates the peak of infection, while enhanced quarantine measures effectively suppress it. This highlights the importance of prompt containment strategies even under more virulent conditions. The sensitivity analysis identifies the infection rate as the most influential parameter driving peak infection, while the quarantine rate exerts the most significant dampening effect. Monte Carlo simulations of parameter uncertainty reveal a consistently high epidemic potential across varied conditions. A parameter sweep across the infection–quarantine space further maps out the conditions under which malware outbreaks can be mitigated or prevented. Overall, the model demonstrates that mobile malware poses sustained epidemic risk under uncertainty, but effective control parameters—particularly quarantine—can drastically alter outbreak trajectories. 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

Small ruminant lentiviruses (SRLVs) are widespread and have a long co-evolutionary history with their hosts, namely sheep and goats. These viruses induce insidious pathologies, causing significant financial losses and animal welfare issues for the affected flocks. In Switzerland, in the 1980s, an eradication campaign was launched targeting these viruses, exclusively in goats, eliminating the virulent SRLV-B strains from the goat population, in which SRLV-B-induced arthritis was prevalent. Nevertheless, although they do not seem to induce clinical diseases, SRLV-A strains continue to circulate in Swiss goats. For this study, we contacted farmers who had animals testing positive for these strains during the census from 2011 to 2012 and visited six of these flocks, conducting serological, virological, and clinical analyses of the animals. We confirmed the absence of SRLV-B; however, we have detected SRLV-A in these flocks. Positive and negative animals lived in close contact for ten years and, except for a small flock of 13 animals, 7 of which tested positive, the transmission of these viruses proved inefficient. None of the positive animals showed any pathology attributable to SRLV infection. These encouraging results allowed us to formulate recommendations for the continued surveillance of these viruses in the Swiss goat population. Full article

Peste des petits ruminants is a highly contagious transboundary viral disease that poses a serious threat to small ruminant populations worldwide. In 2024, seven outbreaks of PPR were recorded in sheep flocks from Timiș County, marking the second confirmed incursions of peste des petits ruminants virus (PPRV) in Romania. This study aimed to document the clinical presentation, pathological findings, and diagnostic confirmation with these field outbreaks. Comprehensive field investigations were carried out between July and September 2024, including clinical examinations, post mortem analysis, serological screening, and molecular detection using reverse transcription polymerase chain reaction (RT-PCR). A total of 13,203 sheep were evaluated, with an overall mortality rate of 12.77%. Characteristic clinical signs included mucopurulent nasal discharge, oral erosions, respiratory distress, and diarrhea. Gross lesions observed during necropsy included hemorrhagic bronchopneumonia, bile-stained liver, catarrhal enteritis, and mucosal hemorrhages. Serological testing revealed flock-level seroprevalence rates ranging from 46.7% to 80.0%, with higher rates observed in older animals. RT-PCR confirmed PPRV infection in all affected flocks. Our findings provide strong evidence of virulent PPRV circulation in an area where the virus had not been reported before. The results highlight an urgent need to strengthen surveillance systems, enhance diagnostic capacity, and foster cross-border collaboration. These field-based insights can contribute to both national and international efforts aimed at controlling and ultimately eradicating the disease. Full article

Sternal bursitis is an underexplored lesion in poultry, often overlooked in microbiological diagnostics. In this study, we characterized 36 Escherichia coli isolates recovered from sternal bursitis in broiler chickens, combining phenotypic antimicrobial susceptibility testing, PCR-based screening, and whole genome sequencing (WGS). The genetic analysis revealed a diverse population spanning 15 sequence types, including ST155, ST201, and ST58. Resistance to tetracycline and ciprofloxacin was common, and several isolates carried genes encoding β-lactamases, including blaTEM-1B. Chromosomal mutations associated with quinolone and fosfomycin resistance (e.g., gyrA p.S83L, glpT_E448K) were also identified. WGS revealed a high number of virulence-associated genes per isolate (58–96), notably those linked to adhesion (fim, ecp clusters), secretion systems (T6SS), and iron acquisition (ent, fep, fes), suggesting strong pathogenic potential. Many isolates harbored virulence markers typical of ExPEC/APEC, such as iss, ompT, and traT, even in the absence of multidrug resistance. Our findings suggest that E. coli from sternal bursitis may act as reservoirs of resistance and virulence traits relevant to animal and public health. This highlights the need for including such lesions in genomic surveillance programs and reinforces the importance of integrated One Health approaches. Full article

Avian pathogenic Escherichia coli (APEC) poses a global threat to poultry health and public safety due to its high lethality, limited treatment options, and potential for zoonotic transmission via the food chain. However, long-term genomic surveillance remains limited, especially in countries like China where poultry farming is highly intensive. This study aimed to characterize the population structure, virulence traits, and antimicrobial resistance of 81 APEC isolates from diseased chickens collected over 16 years from Shandong and neighboring provinces in eastern China. The isolates were grouped into seven Clermont phylogroups, with A and B1 being dominant. MLST revealed 27 STs, and serotyping identified 29 O and 16 H antigens, showing high genetic diversity. The minor phylogroups (B2, C, D, E, G) encoded more virulence genes and had higher virulence-plasmid ColV carriage, with enrichment for iron-uptake, protectins, and extraintestinal toxins. In contrast, the dominant phylogroups A and B1 primarily carried adhesin and enterotoxin genes. Antimicrobial resistance was widespread: 76.5% of isolates were multidrug-resistant. The minor phylogroups exhibited higher tetracycline resistance (mediated by tet(A)), whereas the major phylogroups showed increased resistance to third- and fourth-generation cephalosporins (due to bla_CTX-M-type ESBL genes). These findings offer crucial data for APEC prevention and control, safeguarding the poultry industry and public health. Full article

P. aeruginosa strain NL201 was cultured from an urban water drain in a populated subway underpass as an environmental isolate for the ST111 global high-risk P. aeruginosa clone. In addition to carrying generally present intrinsic P. aeruginosa antibiotic resistance genes, this serotype O4 isolate also carries a set of additional acquired resistance determinants, including aadA2, bla_OXA-10, sul1, and an aac(6′)-Ib family gene. The NL201 isolate features the bla_PDC-3 allele, which was found to confer significantly higher catalytic efficiency against cefepime and imipenem compared to bla_PDC-1, as well as the potent P. aeruginosa virulence factors exoS, exoT, and algD. Serotype O4 isolates of the ST111 global high-risk P. aeruginosa clone have been reported from clinical samples in Canada and the USA, human stool samples in France, and environmental samples (such as cosmetic, hospital drains, and urban water drain) from various European countries. These observations underscore the effective dissemination of the ST111 global high-risk P. aeruginosa clone between different hosts, environments, and habitats, and they warrant targeted investigations from a One Health perspective on the possible routes of its spread and molecular evolution. Full article

Antibiotic resistance has emerged as a critical global public health challenge. In this study, we employed metagenomic sequencing to analyze fecal samples from giant pandas (Ailuropoda melanoleuca) across three distinct stages—semi-wild, released, and wild populations—to investigate shifts in antibiotic resistance genes (ARGs) and virulence factors (VFs) during the reintroduction process. Our findings revealed significant variations in the composition of ARG and VF across different stages, with released and wild giant pandas exhibiting similar ARG and VF profiles. Further analyses identified that the increased abundance of ARGs and VFs in both released and wild individuals compared to semi-wild individuals was mainly from Pseudomonas. We hypothesized that the same geographic environment in which ARGs and VFs are transmitted between a host and the environment via mobile genetic elements (MGEs) may be responsible for the similar structure of ARGs and VFs in released and wild giant pandas. Additionally, diet may modulate the gut microbial community, thereby influencing the distributions of ARG and VF. This study elucidated the impact of geographic and dietary factors on ARGs and VFs dynamics in giant pandas, offering valuable insights for mitigating antibiotic resistance and virulence gene dissemination. Full article

Feline calicivirus (FCV) is a highly contagious pathogen widely circulating in cat populations. FCV has been shown to be able to evade the host immune response through different mechanisms. As a result, following the acute phase of infection, some cats remain persistently infected or experience reinfection cycles with variants of the same strain or with distinct field FCVs. These animals may become asymptomatic carriers, assuming a critical role in virus transmission and posing a significant risk to susceptible cats, particularly in high-density settings. Typical clinical signs of FCV infection include upper respiratory tract disease, oral ulcerations, salivation, and gingivostomatitis. In some cases, FCV infection has also been linked to a range of other clinical manifestations, including severe virulent systemic disease with high mortality rates. Indeed, FCV diversity and evolution have led to the emergence of new genetic, antigenic, and phenotypic variants, challenging disease control. This review provides a comprehensive synthesis of FCV, including its molecular biology, epidemiology, pathogenesis and clinical manifestations. Additionally, the role of vaccination and direct prophylaxis is critically evaluated. An integrated approach is essential to mitigate FCV transmission and disease burden in feline populations. Full article

Biofilm-associated infections caused by Gram-negative bacteria, especially multidrug-resistant strains, frequently occur in intensive care units and represent a major therapeutic challenge. The economic burden of biofilm-associated infections is considerable, making the search for new treatment approaches a focal point for policymakers and scientific funding bodies. Biofilm formation is regulated by quorum sensing (QS), a population density-dependent communication mechanism between cells mediated by small diffusible signaling molecules. QS modulates various intracellular processes, and some features of QS are common to all Gram-negative bacteria. While there are differences in the QS regulatory networks of different Gram-negative bacterial species, a common feature of most Gram-negative bacteria is the ability of N-acylhomoserine lactones (AHL) as inducers to diffuse across the bacterial membrane and interact with receptors located either in the cytoplasm or on the inner membrane. Targeting QS by inhibiting the synthesis, transport, or perception of signaling molecules using small molecules, quorum quenching enzymes, antibodies, combinatorial therapies, or nanoparticles is a promising strategy to combat virulence. In-depth knowledge of biofilm biology, antibiotic susceptibility, and penetration mechanisms, as well as a deep understanding of anti-QS agents, will contribute to the development of antimicrobial therapies to combat biofilm infections. Advancing antimicrobial therapies against biofilm infections requires a deep understanding of biofilm biology, antibiotic susceptibility, penetration mechanisms, and anti-QS strategies. This can be achieved through in vivo and clinical studies, supported by state-of-the-art tools such as machine learning and artificial intelligence. Full article

Klebsiella pneumoniae, a zoonotic pathogen of global concern, poses significant threats to both veterinary and public health. Here, a comparative study characterized 14 clinical isolates (7 avian-derived, 7 human-derived) from Jiangsu, China, through integrated genomic and phenotypic analyses. Firstly, multilocus sequence typing (MLST) revealed distinct epidemiological patterns: the same ST type in avian isolates was circulating between different species and different regions, whereas it was not found in human isolates. In addition, hypervirulent Klebsiella pneumoniae (hvKP) phenotypes confirmed by string test were exclusive to two human isolates (KP15, KP20). Secondly, biofilm detection demonstrated 78.6% (11/14) of isolates possessed biofilm-forming capacity, with cellulose but not curli as the predominant matrix component. Human-derived KP15 and KP20 had the strongest biofilm formation ability in all isolates. Antimicrobial susceptibility profiling identified serious multidrug resistance in both avian and human isolates. Virulence gene analysis revealed striking disparities, with human isolates harboring 10–20 virulence factors (median 15) versus 6–7 (median 6.5) in avian counterparts. Finally, functional pathogenesis assessments demonstrated human-derived strains exhibited stronger epithelial cell adhesion (2-fold higher) and invasion (1.97-fold higher) in Calu-3 cell models and paradoxically showed reduced macrophage phagocytosis (2.85-fold lower at 2 h) for immune escape. In vivo models confirmed dose-dependent mortality, with human isolates demonstrating higher lethality in both Galleria mellonella and mice. Virulence gene burden positively correlated with mortality outcomes. These findings delineate critical host adaptation differences in Klebsiella pneumoniae populations and provide empirical evidence for pathogen transmission dynamics at the human-animal interface. Full article

Drinking water biofilm ecosystems harbor complex and dynamic prokaryotic and eukaryotic microbial communities. However, little is known about the impact of copper corrosion on microbial community functions in metabolisms and resistance. This study was conducted to evaluate the impact of upstream Cu pipe materials on downstream viable community structures, pathogen populations, and metatranscriptomic responses of the microbial communities in drinking water biofilms. Randomly transcribed cDNA was generated and sequenced from downstream biofilm samples of either unplasticized polyvinylchloride (PVC) or Cu coupons. Diverse viable microbial organisms with enriched pathogen-like organisms and opportunistic pathogens were active in those biofilm samples. Cu-influenced tubing biofilms had a greater upregulation of genes associated with potassium (K) metabolic pathways (i.e., K-homeostasis, K-transporting ATPase, and transcriptional attenuator), and a major component of the cell wall of mycobacteria (mycolic acids) compared to tubing biofilms downstream of PVC. Other upregulated genes on Cu influenced biofilms included those associated with stress responses (various oxidative resistance genes), biofilm formation, and resistance to toxic compounds. Downregulated genes included those associated with membrane proteins responsible for ion interactions with potassium; respiration–electron-donating reactions; RNA metabolism in eukaryotes; nitrogen metabolism; virulence, disease, and defense; and antibiotic resistance genes. When combined with our previous identification of biofilm community differences, our studies reveal how microbial biofilms adapt to Cu plumbing conditions by fine-tuning gene expression, altering metabolic pathways, and optimizing their structural organization. This study offers new insights into how copper pipe materials affect the development and composition of biofilms in premise plumbing. Specifically, it highlights copper’s role in inhibiting the growth of many microbes while also contributing to the resistance of some microbes within the drinking water biofilm community. Full article