Infectious Agents Research Articles

Detection and differentiation of fowl adenovirus serotype 4 and duck adenovirus 3 using high resolution melting curve assay

Fowl adenovirus type 4 (FAdV-4) and duck adenovirus type 3 (DAdV-3) are the causative agents of clinical diseases in poultry and have caused considerable economic losses to the waterfowl industry in China. Both FAdV-4 and DAdV-3 are classified into the genus Aviadenovirus under the family Adenoviridae. The high-resolution melting (HRM) assay has become a useful method for virus genotyping, which offers the possibility of rapidly developing a differentiation technique in which the melting profile depends on the GC content of the product in the qPCR platform. The aim of this study was to develop a qPCR-HRM assay for sensitive FAdV-4 and DAdV-3 detection and differentiation. Here, specific primers were designed on the basis of the 100 K genes of FAdV-4 and DAdV-3, and a qPCR-HRM assay was established through optimization of the reaction conditions. A specificity test revealed that this method could detect only FAdV-4 and DAdV-3, with no cross-reaction with other common duck-derived viruses. A sensitivity test revealed that the lowest detection limits of FAdV-4 and DAdV-3 were 2.84 copies/µL and 2.85 copies/µL, respectively. A repeatability test demonstrated that the coefficient of variation was less than 2.5 % in both the intragroup and the intergroup analyses. Field sample distributions of FAdV-4 and DAdV-3 were investigated, and the percentages of DAdV-3-positive, FAdV-4-positive and coinfection-positive in Muscovy ducks were 27.78 %, 16.67 % and 11.11 %, respectively. Further studies are needed to provide more insight into the pathogenesis of FAdV-4 and DAdV-3 coinfection in ducks. In conclusion, the qPCR-HRM assay provides an accurate, sensitive, reliable and cost-effective alternative method for detecting and distinguishing FAdV-4 and DAdV-3.

Role of Rab35 in modulating lipid metabolism and viral entry during pseudorabies virus infection

Pseudorabies virus (PRV), the causative agent of Aujeszky's disease in swine, is a significant pathogen in veterinary medicine. Rab35 is a key regulatory GTPase involved in diverse cellular functions, including endocytic recycling, cytokinesis, and the regulation of the actin cytoskeleton. Although Rab35's roles in these processes are well-documented, its contribution to PRV replication dynamics had not been previously elucidated. Our study demonstrated that PRV infection led to an increase in Rab35 expression at both the mRNA and protein levels in both in vitro cell culture and in vivo models. Elevated Rab35 expression was associated with an acceleration of PRV replication, whereas knocking down Rab35 expression significantly impeded viral proliferation. Further investigation revealed that while Rab35 depletion did not impact the initial attachment of PRV to host cells, it critically suppressed subsequent viral entry and effectively obstructed the transcription of early PRV genes. The downregulation of Rab35 disrupted the expression of enzymes critical to lipid synthesis, which are upregulated during PRV infection. Moreover, Rab35 knockdown disrupted lipid dynamics necessary for the virus to integrate into clathrin-coated pits, a pivotal mechanism for PRV cellular entry. These findings collectively suggest that Rab35 plays a facilitatory role in PRV infection by modulating lipid metabolism and the viral entry process, thereby offering new insights into the complex intracellular mechanisms underlying PRV replication.

The Predominant Role of IgM in Grouper (Epinephelus coioides) Mucosal Defense Against Ectoparasitic Protozoan Infection.

The skin mucosa of fish is exposed to significant challenges from infectious disease agents due to continuous exposure to the aqueous environment. Interestingly, bony fish have evolved to express a unique IgT, which is absent in terrestrials, that appears to play a predominant role in the mucosal-associated lymphoid tissue of the rainbow trout. Nevertheless, in other IgT-producing fish, it is unclear whether IgM or IgT is primarily responsible for protection against infections of cutaneous tissue. Here, we show that grouper IgM appears quickly within the skin following challenge by the marine parasite, Crytopcaryon irritans. These IgM-class antibodies may arise from local proliferating antibody secreting cells or may infiltrate tissue from the serum in dimer polymer form. Based on details of IgM functional responses, we conclude that grouper IgM plays a predominant role in defense against C. irritans.

“Nano knife” for efficient piezocatalytic inactivation of amoeba spores and their intracellular bacteria: Synergetic effect between physical damage and chemical oxidation

Microbial interactions between infectious agents severely interfere with the disinfection process, and current disinfection methods are unable to effectively inactivate intracellular pathogens, posing a new threat to drinking water safety. In this study, we first reported the high efficiency of piezocatalysis in inactivating amoebae and their intracellular bacteria. Results showed that the inactivation rates of the MoS2/rGO piezocatalytic system for amoebic spores and their intracellular bacteria were 4.18 and 5.02-log, respectively, within 180min. Based on scavenger studies and ESR tests, the efficient inactivation of pathogens can be attributed to the generation of reactive oxygen species (ROS), and different pathogens exhibit varying tolerances to distinct ROS. Moreover, TEM analysis revealed that the sharp edge of MoS2/rGO was conducive to the physical cutting of amoeba's cell wall and membrane, promoting the attack of ROS and ensuring a more thorough deactivation. Additionally, the intracellular ROS produced by amoebae is not only conducive to the inactivation of amoebae but also the main reason for the inactivation of bacteria in spores. This study provides a new solution for the inactivation of amoeba spores and their intracellular bacteria and emphasizes the high efficiency of the synergistic effect of physical damage and chemical oxidation.

Prevalence of Helicobacter pylori infection in China from 2014-2023: A systematic review and meta-analysis

BACKGROUND Helicobacter pylori (H. pylori) stands as the predominant infectious agent linked to the onset of gastritis, peptic ulcer diseases, and gastric cancer (GC). Identified as the exclusive bacterial factor associated with the onset of GC, it is classified as a group 1 carcinogen by the World Health Organization. The elimination of H. pylori plays a crucial role in the primary prevention of GC. While the prevalence has declined in recent decades, H. pylori infection is still highly prevalent in China, accounting for a significant part of the disease burden of GC. Therefore, updated prevalence information for H. pylori infection, especially regional and demographic variations in China, is an important basis for the design of targeted strategies that will be effective for the prevention of GC and application of policies for H. pylori control. AIM To methodically evaluate the occurrence of H. pylori infection throughout China and establish a reference point for subsequent investigations. METHODS A systematic review and meta-analysis was conducted following established guidelines, as detailed in our methodology section. RESULTS Our review synthesized data from 152 studies, covering a sample of 763827 individuals, 314423 of whom were infected with H. pylori . We evaluated infection rates in mainland China and the combined prevalence of H. pylori was 42.8% (95%CI: 40.7-44.9). Subgroup analysis indicated the highest prevalence in Northwest China at 51.3% (95%CI: 45.6-56.9), and in Qinghai Province, the prevalence reached 60.2% (95%CI: 46.5-73.9). The urea breath test, which recorded the highest infection rate, showed a prevalence of 43.7% (95%CI: 41.4-46.0). No notable differences in infection rates were observed between genders. Notably, the prevalence among the elderly was significantly higher at 44.5% (95%CI: 41.9-47.1), compared to children, who showed a prevalence of 27.5% (95%CI: 19.58-34.7). CONCLUSION Between 2014 and 2023, the prevalence of H. pylori infection in China decreased to 42.8%, down from the previous decade. However, the infection rates vary considerably across different geographical areas, among various populations, and by detection methods employed.

A rare case of granulomatous mastitis by Brucella species.

Granulomatous mastitis (GM) is a rare, chronic, benign inflammatory disease of the breast. Here, we present a rare case of GM caused by brucellosis and present the first review to compile the cases in the literature. The diagnosis was confirmed by the patient's serological and histopathological results. The patient was successfully treated with doxycycline+rifampicin combination therapy for six weeks. In conclusion, infectious agents, especially brucellosis, should be considered in the differential diagnosis of GM in endemic regions. Diagnostic methods, such as tissue culture and serological tests, should be used to detect possible infectious agents if necessary.

Revisiting tuberculosis diagnosis: the prospect of urine lipoarabinomannan assay as a diagnostic tool in people living with human immunodeficiency virus

Abstract Background Tuberculosis, since its discovery has become a global health burden, continuously spreading across the nations of the earth with increased mortality. Its effect on human immunodeficiency virus (HIV) progression and immune cell deterioration cannot be overlooked. The widespread use of traditional and molecular TB diagnostic methods has been hindered by several factors. Nonetheless, the development of a rapid, sensitive, timely, non-invasive diagnostic protocol could revolutionise the diagnostic era and halt the spread of this infectious agent. It could also help in the early diagnosis of the infection in poorly developed areas. The detection efficacy of urine lipoarabinomannan assay as a prospect in tuberculosis diagnosis in HIV-positive patients was assessed in this study. Urine samples were collected into a wide-mouthed universal container from HIV-positive patients with signs and symptom of tuberculosis and HIV advanced disease. Alere determine urine lateral flow—LAM test was used for the detection of LAM antigen in urine samples of HIV-positive patients. The CD4 count of the HIV-positive patients was also documented. Results A total of 85 HIV-positive subjects were included in the analysis based on the inclusion criteria. Urinary LAM was reactive in 29 (34.1%) of 85 HIV-positive patients and non-reactive in 56 (69.1%). The majority of the participants had a CD4+ count < 200 cells/µL 60 (70.6%), while others had CD4+ count ≥ to 200 cells/µL 25 (29.4%). There was no statistically significant difference between CD4 count and LAM positivity. Most of the affected age groups in the study were 31–45 years, and females had preponderance in comparison to male subjects. Conclusions The use of urinary LAM in HIV-positive patients is a helpful tool for TB screening. It also has a promising ability for early TB diagnosis in the study group and other TB-associated disease conditions in resource-deprived settings. For the general populace, further research is required to certify its sensitivity and specificity.

Plant derived bioactive compounds for the treatment of neurodegeneration and neuroimmune disorders associated with the complement system

The complement system is a key component of the innate immune system that mediates the clearance of pathogens, apoptotic cells, and cellular debris. However, the complement system also has diverse roles in the central nervous system (CNS), where it regulates synaptic pruning, neural plasticity, and neuroinflammation. Dysregulation of the complement system has been implicated in various neurodegenerative disorders such as Alzheimer’s disease, multiple sclerosis, epilepsy, stroke, and traumatic brain injury. In these conditions, excessive or chronic activation of the complement system may lead to synaptic loss, neuronal damage, immune dysregulation, and inflammation, which leads to exacerbating the disease’s progression and severity. Moreover, the complement system may interact with infectious agents that invade the CNS, such as bacteria, viruses, fungi, and parasites, and modulate their pathogenicity and host response. Therefore, understanding the complex interplay between the complement system and the CNS is crucial for developing novel therapeutic strategies to prevent or treat neurodegenerative and neuroimmune disorders. Natural compounds, such as plant extracts, phytochemicals, and nutraceuticals, have emerged as promising candidates for modulating the complement system and its effects on the CNS. These compounds may exert anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory effects by regulating the expression of various complement components and pathways. In this review, we summarized the current knowledge on the roles of the complement system in human neurodegenerative disorders and the benefits of natural compounds for complement-targeted therapy.

Enriching the future of public health microbiology with hybridization bait capture.

SUMMARYPublic health microbiology focuses on microorganisms and infectious agents that impact human health. For years, this field has relied on culture or molecular methods to investigate complex samples of public health importance. However, with the increase in accuracy and decrease in sequencing cost over the last decade, there has been a transition to the use of next-generation sequencing in public health microbiology. Nevertheless, many available sequencing methods (e.g., shotgun metagenomics and amplicon sequencing) do not work well in complex sample types, require deep sequencing, or have inherent biases associated with them. Hybridization bait capture, also known as target enrichment, brings in solutions for such limitations. It is an increasingly popular technique to simultaneously characterize many thousands of genetic elements while reducing the amount of sequencing needed (thereby reducing the sequencing costs). Here, we summarize the concept of hybridization bait capture for public health, reviewing a total of 35 bait sets designed in six key topic areas for public health microbiology [i.e., antimicrobial resistance (AMR), bacteria, fungi, parasites, vectors, and viruses], and compare hybridization bait capture to previously relied upon methods. Furthermore, we provide an in-depth comparison of the three most popular bait sets designed for AMR by evaluating each of them against three major AMR databases: Comprehensive Antibiotic Resistance Database, Microbial Ecology Group Antimicrobial Resistance Database, and Pathogenicity Island Database. Thus, this article provides a review of hybridization bait capture for public health microbiologists.

Swine Industry in Canada: Biosecurity in Live Animal, Semen Transportation, and Embryo Transfer

The pork industry, a key player in the Canadian economy, significantly contributes to livestock production, international trade markets, and employment. The multi-faceted swine industry is comprised of nucleus, multiplier, and commercial herds. The recognition and application of exemplary internal and external biosecurity measures are paramount for maintaining sustainable swine production. Historically, live animal transport has been an important means of disseminating superior genetics between production herds and poses a considerable risk for disease transmission and biosecurity breach points. The industry has evolved over time to employ other methods, through the shipping of boar semen and the adoption of artificial insemination practices to acquire genetic resources with a lower risk of disease transmission. These effective changes have led to an improvement in herd health, production performance, and efficiency. In particular, the industry’s dedication to enhanced biosecurity is evident in the effort to streamline embryo collection and transfer procedures. Such advances reduce the potential need to transport live animals, thereby lowering the risk of introducing infectious agents. This review article explores the different forms of disseminating swine genetics, namely, live animal, semen transportation, and embryo transfer, examining potential breaches in biosecurity, and discussing mitigation strategies that reduce disease transmission to protect the health of animal stock.

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases

Metagenomic next-generation sequencing (mNGS) is a transformative approach in the diagnosis of infectious diseases, utilizing unbiased high-throughput sequencing to directly detect and characterize microbial genomes from clinical samples. This review comprehensively outlines the fundamental principles, sequencing workflow, and platforms utilized in mNGS technology. The methodological backbone involves shotgun sequencing of total nucleic acids extracted from diverse sample types, enabling simultaneous detection of bacteria, viruses, fungi, and parasites without prior knowledge of the infectious agent. Key advantages of mNGS include its capability to identify rare, novel, or unculturable pathogens, providing a more comprehensive view of microbial communities compared to traditional culture-based methods. Despite these strengths, challenges such as data analysis complexity, high cost, and the need for optimized sample preparation protocols remain significant hurdles. The application of mNGS across various systemic infections highlights its clinical utility. Case studies discussed in this review illustrate its efficacy in diagnosing respiratory tract infections, bloodstream infections, central nervous system infections, gastrointestinal infections, and others. By rapidly identifying pathogens and their genomic characteristics, mNGS facilitates timely and targeted therapeutic interventions, thereby improving patient outcomes and infection control measures. Looking ahead, the future of mNGS in infectious disease diagnostics appears promising. Advances in bioinformatics tools and sequencing technologies are anticipated to streamline data analysis, enhance sensitivity and specificity, and reduce turnaround times. Integration with clinical decision support systems promises to further optimize mNGS utilization in routine clinical practice. In conclusion, mNGS represents a paradigm shift in the field of infectious disease diagnostics, offering unparalleled insights into microbial diversity and pathogenesis. While challenges persist, ongoing technological advancements hold immense potential to consolidate mNGS as a pivotal tool in the armamentarium of modern medicine, empowering clinicians with precise, rapid, and comprehensive pathogen detection capabilities.

SHEA practice update: infection prevention and control (IPC) in residential facilities for pediatric patients and their families.

In 2011, the Society for Healthcare Epidemiology of America (SHEA) and Ronald McDonald House Charities® (RMHC®) established a formal collaboration to develop the first IPC guideline. Both organizations agreed that RMH programs staff and other organizations operating similar programs would benefit from a standardized approach. In 2023, the collaboration was re-established to revise and update the original IPC guideline. This SHEA Practice Update on "Infection Prevention and Control (IPC) in Residential Facilities for Pediatric Patients and Their Families" addresses preventing transmission of infectious agents in "home away from home" residential settings, of which the Ronald McDonald Houses (RMHs) serve as a prototype.

Development of an operational trap for collection, killing, and preservation of triatomines (Hemiptera: Reduviidae): the kissing bug kill trap.

Surveillance of triatomines or kissing bugs (Hemiptera: Reduviidae: Triatominae), the insect vectors of Trypanosoma cruzi, a Chagas disease agent, is hindered by the lack of an effective trap. To develop a kissing bug trap, we made iterative improvements over 3 years on a basic design resulting in 7 trap prototypes deployed across field sites in Texas, United States and Northern Mexico, yielding the capture of 325 triatomines of 4 species (Triatoma gerstaeckeri [Stål], T. sanguisuga [LeConte], T. neotomae [Neiva], and T. rubida [Uhler]). We began in 2019 with vertical transparent tarpaulin panel traps illuminated with artificial light powered by AC current, which were successful in autonomous trapping of flying triatomines, but were expensive, labor-intensive, and fragile. In 2020, we switched to white LED lights powered by a solar cell. We tested a scaled-down version of the vertical panel traps, a commercial cross-vane trap, and a multiple-funnel trap. The multiple-funnel traps captured 2.6× more kissing bugs per trap-day than cross-vane traps and approached the performance of the vertical panel traps in number of triatomines captured, number of triatomines per trap-day and triatomines per arthropod bycatch. Multiple-funnel traps required the least labor, were more durable, and had the highest triatomines per day per cost. Propylene glycol in the collection cups effectively preserved captured triatomines allowing for molecular detection of T. cruzi. The trapping experiments established dispersal patterns for the captured species. We conclude that multiple-funnel traps with solar-powered LED lights should be considered for adoption as surveillance and potentially mass-trapping management tools for triatomines.

Current vaccines, experimental immunization trials, and new perspectives to control selected vector borne blood parasites of veterinary importance

Parasite infections transmitted by vectors such as ticks and blood-sucking arthropods pose a significant threat to both human and animal health worldwide and have a substantial economic impact, particularly in the context of worsening environmental conditions. These infections can manifest in a variety of symptoms, including fever, anemia, jaundice, enlarged spleen, neurological disorders, and lymphatic issues, and can have varying mortality rates. In this review, we will focus on the current state of available vaccines, vaccine research approaches, and trials for diseases caused by vector-borne blood parasites, such as Babesia, Theileria, Anaplasma, and Trypanosoma, in farm animals. Control measures for these infections primarily rely on vector control, parasiticidal drug treatments, and vaccinations for disease prevention. However, many of these approaches have limitations, such as environmental concerns associated with the use of parasiticides, acaricides, and insecticides. Additionally, while some vaccines for blood parasites are already available, they still have several drawbacks, including practicality issues, unsuitability in non-endemic areas, and concerns about spreading other infectious agents, particularly in the case of live vaccines. This article highlights recent efforts to develop vaccines for controlling blood parasites in animals. The focus is on vaccine development approaches that show promise, including those based on recombinant antigens, vectored vaccines, and live attenuated or genetically modified parasites. Despite intensive research, developing effective subunit vaccines against blood stage parasites remains a challenge. By learning from previous vaccine development efforts and using emerging technologies to define immune mechanisms of protection, appropriate adjuvants, and protective antigens, we can expand our toolkit for controlling these burdensome diseases.

Investigating the Antagonistic Effects of Novel Combination Fungicides against Fusarium oxysporum f. sp. ricini under In-vitro Conditions

Aim: The study aimed to assess the efficacy of nine novel fungicide combinations against Fusarium oxysporum f. sp. ricini, the causal agent of wilt disease in castor. Methodology: The efficacy of fungicides was evaluated using the poisoned food technique under in-vitro conditions. Radial mycelial growth of the pathogen was measured across various concentrations (100 to 1000 ppm) of the fungicide combinations to determine their impact on mycelial inhibition. Results: Results indicated a substantial reduction in radial mycelial growth with increased fungicide concentration. Among the tested fungicides, Tebuconazole + Trifloxystrobin and Prochloraz + Tebuconazole recorded complete mycelial inhibition (100 %) at all the tested concentrations, demonstrating significant fungicidal activity followed by Hexaconazole + Captan with a mean mycelial inhibition of 85.2 %, indicating strong potential for disease management. In contrast, the least mean mycelial inhibition (24.7 %) was observed with Thiophanate methyl + Pyraclostrobin. Conclusion: These findings underscored the importance of selecting effective fungicide combinations to manage F. oxysporum f. sp. ricini, thereby enhancing crop protection and agricultural sustainability.

HCV infection activates the proteasome via PA28γ acetylation and heptamerization to facilitate the degradation of RNF2, a catalytic component of polycomb repressive complex 1.

We previously reported that hepatitis C virus (HCV) infection or HCV core protein expression induces HOX gene expression by impairing histone H2A monoubiquitination via a proteasome-dependent reduction in the level of RNF2, a key catalytic component of polycomb repressive complex 1 (H. Kasai, K. Mochizuki, T. Tanaka, A. Yamashita, et al., J Virol 95:e01784-20, 2021, https://doi.org/10.1128/jvi.01784-20). In this study, we aimed to investigate the mechanism by which HCV infection accelerates RNF2 degradation. Yeast two-hybrid screening and an immunoprecipitation assay revealed that RNF2 is a PA28γ-binding protein. The proteasome activator PA28γ destabilized the RNF2 protein in a proteasome-dependent manner, since RNF2 degradation was impaired by PA28γ knockout or MG132 treatment. HCV infection or core protein expression reduced the levels of RNF2 and histone H2A K119 monoubiquitination and induced the expression of HOX genes in the presence of PA28γ, while PA28γ knockout reversed these changes. Treatment with a lysine acetyltransferase inhibitor inhibited the acetylation of PA28γ at K195 and the degradation of the RNF2 protein, while treatment with a lysine deacetylase inhibitor accelerated these events in a PA28γ-dependent manner. RNF2 protein degradation was increased by expression of the acetylation mimetic PA28γ mutant but not by expression of the acetylation-defective mutant or the proteasome activation-defective mutant. Furthermore, HCV infection or core protein expression facilitated the interaction between PA28γ and the lysine acetyltransferase CBP/p300 and then accelerated PA28γ acetylation and heptazmerization to promote RNF2 degradation. These data suggest that HCV infection accelerates the acetylation-dependent heptamerization of PA28γ to increase the proteasomal targeting of RNF2.IMPORTANCEHCV is a causative agent of HCV-related liver diseases, including hepatic steatosis, cirrhosis, and hepatocellular carcinoma. PA28γ, which, in heptameric form, activates the 20S core proteasome for the degradation of PA28γ-binding proteins, is responsible for HCV-related liver diseases. HCV core protein expression or HCV infection accelerates RNF2 degradation, leading to the induction of HOX gene expression via a decrease in the level of H2Aub on HOX gene promoters. However, the mechanism of RNF2 degradation in HCV-infected cells has not been clarified. The data presented in this study suggest that PA28γ acetylation and heptamerization are promoted by HCV infection or by core protein expression to activate the proteasome for the degradation of RNF2 and are responsible for HCV propagation. This study provides novel insights valuable for the development of therapies targeting both HCV propagation and HCV-related diseases.

Microbial Profile and Antimicrobial Resistance in Enteric Pathogens of Farmed Catfish (Pangasianodon hypophthalmus) in Tropical Freshwater Farms

Background: Recently, Pangasianodon hypophthalmus has emerged as an important fish species farmed in India, contributing to food security in the region. Understanding the bacterial flora associated with this fish is essential to ensure food safety, particularly in the Indian context where such studies have been limited. Objective: This study aims to determine the aerobic bacterial flora and antimicrobial resistance in enteric pathogens associated with farmed Pangasianodon hypophthalmus cultured in freshwater ponds in Kerala, India. Methods: The study included enumeration of aerobic plate counts, Pseudomonads, Aeromonas, Enterobacteriaceae and Staphylococcus aureus using standard methods. Bacterial identification was performed using analytical profile index 20E (APE20E) and 16s rDNA sequencing. Antimicrobial resistance was assessed in E. coli, S. aureus and Aeromonas species using disc diffusion assays. Results: The aerobic bacterial flora in catfish muscle tissue included H2S-producing bacteria, Enterobacteriaceae, Pseudomonas, Aeromonas, and B. thermosphacta. Dominant genera identified were Pseudomonas, Burkholderia, Stenotrophomonas, Aeromonas, Klebsiella, and Psychrobacter. Multidrug-resistant strains of enterotoxigenic E. coli and A. hydrophila were recovered, raising concerns about the prevalence of multidrug resistance in A. hydrophila, an etiological agent of red disease in farmed catfish. Conclusion: This study highlights the microbiological risks posed by Aeromonas spp. and enterotoxigenic E. coli in farmed catfish, emphasising their potential as vectors for pathogenic and antibiotic-resistant determinants in the food chain. Recommendations for future research should focus on the development of effective biopreservatives to control these pathogens in processed Pangasius products.

Do white-footed mice, the main reservoir of the Lyme disease pathogen in the United States, clinically respond to the borrelial tenancy?

As white-footed mice, Peromyscus leucopus, are considered the primary animal reservoir of Borreliella burgdorferi sensu stricto (Bb), the main agent of Lyme disease (LD) in the United States, these animals represent the most relevant model to study borrelial spirochetes in the context of their natural life cycle. Previous studies have consistently demonstrated that although white-footed mice respond immunologically to the invasion of the Lyme pathogen, P. leucopus adults do not develop a clinically detectable disease. This tolerance, which is common for mammalian reservoirs of different pathogens, contrasts with detrimental anti-borrelial responses of C3H mice, a widely used animal model of LD, which always result in a clinical manifestation (e.g., arthritis). The current investigation is a follow-up of our recent study that already showed a relative quiescence of the spleen transcriptome for Bb-infected white-footed mice compared to the infected C3H mice. In an effort to identify the mechanism behind this tolerance, in this study, we have evaluated an extensive list of hematological and biochemical parameters measured in white-footed mice after their 70-day-long borrelial infection. Despite missing reference intervals for Peromyscus mice, our sex- and age-matched uninfected controls allowed us to assess the blood and serum parameters. In addition, for our assessment, we also utilized behavioral, immunological, and histological analyses. Collectively, by using the metrics reported herein, the present results have demonstrated clinical unresponsiveness of P. leucopus mice to the borrelial infection, presenting no restriction to a long-term host-pathogen co-existence.

Overexpression of outer membrane protein A (OmpA) increases aminoglycoside sensitivity in mycobacteria.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex infection, is a leading cause of death worldwide from a single infectious agent. The emergence of drug resistance Mtb clinical strains makes the situation more serious. The role of Mtb outer membrane protein A (OmpA) in antimicrobial resistance remains unclear. This study aimed to evaluate the effect of OmpA expression on mycobacterial drug resistance. In this study, a Mycobacterium smegmatis (Ms) strain overexpressing OmpA (Ms-OmpA) and a Mycobacterium bovis (Mb) strain overexpressing OmpA (Mb-OmpA) were constructed, and their susceptibility to anti-TB drugs was determined by performing the minimal inhibitory concentrations (MICs), the plate assay and the macrophage infection assays. The streptomycin MIC of the overexpressing strain was 2-fold lower than those of the wide-type (Ms) and empty plasmid strains (pMV-261) as well as amikacin and gentamicin. Moreover, both the plate and the macrophage infection assays indicate that overexpression of OmpA increases streptomycin sensitivity in Mycobacteria. The other aminoglycosides like amikacin and gentamicin have the same phenotypes as streptomycin on the plates for the virulent strain Mb-OmpA. The porin inhibitor spermidine can increase streptomycin tolerance in the overexpressing strain, and overexpressing OmpA can increase the intracellular accumulation of hydrophilic ethidium bromide, which indicates that porin protein OmpA contributes to aminoglycosides sensitivity in Mycobacteria. In this study, we have characterized the contribution of OmpA in the antimicrobial resistance phenotype of Mycobacteria, which may provide valuable insights for understanding antibiotic resistance and designing new strategies for TB treatment.

The hidden role of buffalo trade network in bovine epidemic spreading.

Animal movements are a key factor in the spread of pathogens. Consequently, network analysis of animal movements is a well-developed and well-studied field. The relationships between animals facilitate the diffusion of infectious agents and, in particular, shared environments and close interactions can facilitate cross-species transmission. Cattle are often the focus of these studies since they are among the most widely distributed and traded species globally. This remains true for Italy as well, but with an important additional consideration. Indeed, another important productive reality in the peninsula is buffalo farming. These farms have an interesting characteristic: approximately two-thirds of them also rear cattle. This coexistence between cattle and buffalo could have an impact on the diffusion of pathogens. Given that buffalo farms are often overlooked in the literature, the primary goal of this work is to investigate the potential consequences of omitting buffalo from cattle network analyses. To investigate this impact, we will focus on Q fever, a disease that can infect both species and is present on the Italian territory and for which the impact of the buffalo population has not been thoroughly studied, and simulate its spread to the farms of both species through compartmental models. Our analysis reveals that despite the significant difference in network sizes, the unique characteristic of Italian buffalo farms makes the buffalo network essential for a comprehensive understanding of bovine disease dynamics in Italy.