Agents Of Infections Research Articles

Presence and Role of the Type 3 Fimbria in the Adherence Capacity of Enterobacter hormaechei subsp. hoffmannii.

Enterobacter hormaechei, one of the species within the Enterobacter cloacae complex, is a relevant agent of healthcare-associated infections. In addition, it has gained relevance because isolates have shown the capacity to resist several antibiotics, particularly carbapenems. However, knowledge regarding colonization and virulence mechanisms of E. hormaechei has not progressed to the same extent as other Enterobacteriaceae species as Escherichia coli or Klebsiella pneumoniae. Here, we describe the presence and role of the type 3 fimbria, a chaperone-usher assembled fimbria, which was first described in Klebsiella spp., and which has been detected in other representatives of the Enterobacteriaceae family. Eight Chilean E. cloacae isolates were examined, and among them, four E. hormaechei isolates were found to produce the type 3 fimbria. These isolates were identified as E. hormaechei subsp. hoffmannii, one of the five subspecies known. A mutant E. hormaechei subsp. hoffmannii strain lacking the mrkA gene, encoding the major structural subunit, displayed a significantly reduced adherence capacity to a plastic surface and to Caco-2 cells, compared to the wild-type strain. This phenotype of reduced adherence capacity was not observed in the mutant strains complemented with the mrkA gene under the control of an inducible promoter. Therefore, these data suggest a role of the type 3 fimbria in the adherence capacity of E. hormaechei subsp. hoffmannii. A screening in E. hormaechei genomes contained in the NCBI RefSeq Assembly database indicated that the overall presence of the type 3 fimbria is uncommon (5.94-7.37%), although genes encoding the structure were detected in representatives of the five E. hormaechei subspecies. Exploration of complete genomes indicates that, in most of the cases, the mrkABCDF locus, encoding the type 3 fimbria, is located in plasmids. Furthermore, sequence types currently found in healthcare-associated infections were found to harbor genes encoding the type 3 fimbria, mainly ST145, ST78, ST118, ST168, ST66, ST93, and ST171. Thus, although the type 3 fimbria is not widespread among the species, it might be a determinant of fitness for a subset of E. hormaechei representatives.

An energy coupling factor transporter of Streptococcus sanguinis impacts antibiotic susceptibility as well as metal and membrane homeostasis.

Streptococcus sanguinis is a prevalent member of human microbiome capable of acting as a causative agent of oral and respiratory infections. S. sanguinis competitive success within the infection niche is dependent on acquisition of metal ions and vitamins. Among the systems that bacteria use for micronutrient uptake is the energy coupling factor (ECF) transporter system EcfAAT. Here we describe physiological changes arising from EcfAAT transporter disruption. We found that EcfAAT contributes to S. sanguinis antibiotic sensitivity as well as metal and membrane homeostasis. Specifically, our work found that disruption of EcfAAT results in increased polymyxin susceptibility. We performed assessment of cell-associated metal content and found depletion of iron, magnesium, and manganese. Furthermore, membrane composition analysis revealed significant enrichment in unsaturated fatty acid species resulting in increased membrane fluidity. Our results demonstrate how disruption of a single EcfAAT transporter can have broad consequences on bacterial cell homeostasis. ECF transporters are of interest within the context of infection biology in bacterial species other than streptococci, hence work described here will further the understanding of how micronutrient uptake systems contribute to bacterial pathogenesis.

Inhibition of porcine reproductive and respiratory syndrome virus replication by rifampicin in vitro.

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause significant economic losses to the global swine industry, yet effective prevention and control measures remain elusive. The development of novel antivirals is thus urgently needed. Rifampicin (RFP), a semisynthetic derivative of rifamycin, has been previously reported to inhibit the replication of certain mammalian DNA viruses as well as RNA viruses. In this study, we unveil RFP as a potent inhibitor of PRRSV both in Marc-145 cells (half-maximal inhibitory concentration 61.26 μM) and porcine alveolar macrophages (half-maximal inhibitory concentration 53.09 μM). The inhibitory effect of RFP occurred during viral replication rather than binding, internalization and release. We also demonstrated that RFP inhibits PRRSV proteins production in the early stage of infection, without inhibiting host protein synthesis. Moreover, RFP effectively restricted porcine epidemic diarrhea virus (PEDV) and porcine enteric alphacoronavirus (PEAV) infection in Vero cells. In summary, these findings indicate the promising potential of RFP as a therapeutic agent for PRRSV, PEDV and PEAV infection in pig farms.

Feasibility of Narrow-Spectrum Antimicrobial Agents for Post-Operative Intra-Abdominal Infections After Gastrectomy.

Introduction: Recently, antimicrobial resistance has received considerable attention. Broad-spectrum antimicrobial agents are recommended as the initial therapy for post-operative intra-abdominal infections. However, at our institution, we have adopted a tactic of initially treating post-operative intra-abdominal complications with relatively narrow-spectrum antimicrobial agents, such as second-generation cephalosporins. In the present study, we aimed to retrospectively analyze the use of antimicrobial agents and the resulting treatment outcomes in patients with intra-abdominal complications after gastrectomy at our facility. Methods: We conducted a retrospective observational study of patients treated with antibiotic agents for intra-abdominal infectious complications after gastrectomy between 2011 and 2021. We determined the proportion of "initial treatment failures" associated with the initial administration of antibiotic agents for post-operative intra-abdominal complications. Results: Post-operative intra-abdominal infections were observed in 29 patients. Broad-spectrum antimicrobial agents were not administered. We successfully treated 19 patients. Initial treatment failure was observed in 10 patients, of whom five experienced failure due to bacterial resistance to the initial antimicrobial agent. All 10 patients who experienced initial treatment failure were discharged after drainage procedures or other treatments. There were no deaths due to post-operative complications. Cefmetazole was used as the initial antimicrobial agent in 27 of the 29 patients. Conclusions: Considering that all patients with post-gastrectomy intra-abdominal infections were successfully treated using relatively narrow-spectrum antimicrobial agents, and initial treatment failure due to antimicrobial-resistant pathogens was 17.2%, the use of narrow-range antimicrobial agents for intra-abdominal infections after gastrectomy can be deemed appropriate.

Prevalence of ESKAPE pathogens and Antibiotic Susceptibility Status in Skin and Soft Tissue Infections from a tertiary care teaching hospital in South India

Background: ESKAPE “(Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter sp.)” pathogens are commonly found in infections affecting the skin and underlying tissues. ESKAPE pathogens often exhibit widespread multidrug resistance in hospitals, contributing significantly to Hospital-acquired infections. ESKAPE pathogen prevalence can combat the vast challenge of Antibiotic Resistance (ABR). Materials and Methods: “The microbiological statistics of ESKAPE infections and sensitivity between January 2020 and October 2022 were extracted from the laboratory records and analysed for the bacterial profile and antibiotic sensitivity pattern”. Results: Out of the 2037 pathogens isolated from Skin and soft tissue infection, 1308 were ESKAPE pathogens accounting for a prevalence of 64.2%. Staphylococcus aureus (n=340/1308; 25.99%) was the predominant pathogen followed by Pseudomonas aeruginosa (n=332/1308; 25.38%). Among Gram-negative isolates, 29.43% exhibited multidrug resistance (MDR). Carbapenemase was found to be a frequent mechanism of resistance, highest among Acinetobacter species (n=99; 64.7%), followed by Klebsiella pneumoniae (n=109; 37.07%). Amp C production was seen most commonly in Enterobacter species (n=93; 61.2%), followed by Klebsiella pneumoniae (n=172; 58.5%) whereas ESBL production was seen in Enterobacter species (n=46; 30.03%). Conclusion: ESKAPE pathogens are critical etiologic agents of Skin and soft infections. Regular studies are vital for evaluating bacterial susceptibility and highlighting the importance of policies to reduce hospital infections and enhance antibiotic prescription oversight. Understanding virulence and resistance markers is critical for tailoring treatment strategies based on local antibiograms and managing related infections.

Investigating the anti-inflammatory potential of Elaeagnus an-gustifolia L. through enzyme inhibition assays

Elaeagnaceae family, which is common in the steppe regions of Asia, Europe, and North America, contains about 45 species, including three genus: Hippophae, Shepherdia, and Elaeagnus. There are two species in the genus Hippophae rhamnoides and Elaeagnus angustifolia. The species of the Elaeagnaceae family is widely used in public and traditional medicine due to its widespread prevalence in the world and in Turkey. Ethnobotanical field studies have revealed that the fruits of E. angustifolia L. are used in Anatolia as an anti-inflammatory, antipyretic, urolithiatic, antidiarrheal, and anti-inflammatory agent in eye infections. Furthermore, the fruit of this plant is consumed as an appetizer and a source of nutrition. The study aims to evaluate the in vitro anti-inflammatory activity of extracts in different polarities from the leaves, branches, and fruits of E. angustifolia and to establish the content of polyphenolic compounds (flavones and polyphenolic carboxylic acids) in the ethyl acetate extract branches using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). In this context, the anti-inflammatory effects of n-hexane, ethyl acetate, and methanol extracts prepared from the plant have been evaluated through in vitro cyclooxygenase (COX-1 and COX-2) enzyme inhibition, inhibition of protein denaturation and proteinase enzyme, and anti-lipoxygenase activity tests. The results showed the highest activity of the ethyl acetate extract from branches. The HPLC-MS analysis revealed that the ethyl acetate extract prepared from the branches at a concentration of 100 mg/g contains p-coumaric acid (123.91 mg%), ferulic acid (62.07 mg%), kaempferol (43.11 mg%), sinapic acid (9.82 mg%), and quercetol (12.46 mg%). It was concluded that the data obtained in this context supported the use of the plant in folk medicine.

Zinc oxide nanoparticles loaded with linalool as a potential control agent of malaria infection

This research aimed to produce and analyze zinc oxide nanoparticles (ZNPs) loaded with linalool (LZNPs), and to evaluate their in vitro and in vivo efficacy through targeting the inflammation and oxidative stress. LZNPs were synthesized using an ethanolic solution of polyvinyl alcohol. The Malstat technique was used to evaluate the effectiveness of LZNPs against both sensitive and resistant strains of Plasmosium falciparum. In vivo effects of ZNPs and LZNPs on parasite growth suppression, survival rate, oxidative stress markers, antioxidant genes, and gene and protein levels of inflammatory cytokines were evaluated by Real-time PCR and Western blot techniques. The results indicated that LZNPs demonstrated noteworthy (P < 0.001) antiplasmodial activity against both susceptible and resistant strains of P. falciparum. P. berghei NK65 strain-infected mice treated with the ZNPs and LZNPs at doses of 5–15 mg/kg notably (p < 0.001) increased the survival rates and parasite growth suppression. LZNPs at 5–15 mg/kg demonstrated a significant (p < 0.001) decrease in oxidative stress markers, increased the expression level of antioxidant genes, and reduced the gene and protein expression level of inflammatory cytokines. The current experimental study demonstrated the potent in vitro antiplasmodial activity of LZNPs against chloroquine-resistant and sensitive strains of P. falciparum compared to ZNPs alone. Additionally, the study identified the potential benefits of this nanocomposite in suppressing the parasite and extending the survival rate in mice infected with P. berghei by targeting inflammation and oxidative stress. It also showed minimal toxicity in liver and kidney function in healthy mice. Nevertheless, further research is essential to elucidate the comprehensive mechanisms and practical effectiveness of LZNPs.

Antimicrobial Effect of Cinnamomum verum Leaf Extract on Fungus and MDR Bacteria

Multi-drug resistance is a major concern to medical science across the globe. The inability of most drugs to destroy different pathogenic bacteria and fungi demands the use of natural products like phytochemicals to treat various infections. At this juncture, Cinnamomum verum is an active agent against various bacteria and fungi. C. verum or true cinnamon is widely used as a spice. It has several medicinal values and is widely accepted as traditional medicine. Cinnamaldehyde is the most active compound of C. verum that is responsible for its antimicrobial activity. In this study, the minimum inhibitory concentration (MIC) of C. verum leaf ethanolic extract was determined against different bacteria and fungi along with ethanol as a control. The extract showed remarkable antifungal action on Candida albicans and antibacterial action against Pseudomonas aeruginosa with a MIC value of only 0.039 mg/ml. The MIC value against other microorganisms ranges from 0.78 mg/ml to 25mg/ml. C. verum leaf extract can be used as an effective antimicrobial agent in fungal and bacterial infections.

Hydropneumothorax as a rare manifestation of primary pulmonary hydatid disease

Echinococcosis, alternatively referred to as hydatid disease, is caused by the larvae of the tapeworm Echinococcus. The primary agents of human infections are Echinococcus granulosus and Echinococcus multilocularis. The present case report pertains to an individual who relocated from an endemic region to the United Arab Emirates and subsequently manifested symptoms of hydropneumothorax. The 44-year-old male patient presented with a 4-day fever and right-sided chest pain, accompanied by cough and breathlessness for 2 weeks. Computed tomography (CT) of the chest revealed right hydropneumothorax and a ruptured hydatid cyst with consolidation. The patient was diagnosed with a ruptured pulmonary hydatid cyst based on a strongly positive hydatid serology and the presence of hydatid tissue on histopathological examination. The patient underwent surgical decortication with cyst removal and received medical treatment with ceftriaxone and albendazole. He was discharged in good condition after a 10-day hospitalisation period. Echinococcosis is a parasitic disease that most often affects the liver and lungs. Although more than half of the patients do not show any symptoms, the main symptoms observed during presentation include dry cough, haemoptysis, and chest pain. Plain radiographs or chest CT scans are used for diagnosis. Surgery is considered the primary treatment for pulmonary hydatid cysts and medical treatment with benzimidazoles (albendazole and mebendazole) is recommended. Complicated pulmonary hydatid disease can manifest in various ways, including hydropneumothorax, as observed in the present case. Early diagnosis, surgical intervention combined with medical treatment, and multidisciplinary teamwork can significantly improve patient outcomes.

Computational prediction of crucial genes involved in gonorrhea infection and neoplastic cell transformation: A multiomics approach

Neisseria gonorrheae, the causative agent of genitourinary infections, has been associated with asymptomatic or recurrent infections and has the potential to form biofilms and induce inflammation and cell transformation. Herein, we aimed to use computational analysis to predict novel associations between chronic inflammation caused by gonorrhea infection and neoplastic transformation. Prioritization and gene enrichment strategies based on virulence and resistance genes utilizing essential genes from the DEG and PANTHER databases, respectively, were performed. Using the STRING database, protein‒protein interaction networks were constructed with 55 nodes of bacterial proteins and 72 nodes of proteins involved in the host immune response. MCODE and cytoHubba were used to identify 12 bacterial hub proteins (murA, murB, murC, murD, murE, purN, purL, thyA, uvrB, kdsB, lpxC, and ftsH) and 19 human hub proteins, of which TNF, STAT3 and AKT1 had high significance. The PPI networks are based on the connectivity degree (K), betweenness centrality (BC), and closeness centrality (CC) values. Hub genes are vital for cell survival and growth, and their significance as potential drug targets is discussed. This computational study provides a comprehensive understanding of inflammation and carcinogenesis pathways that are activated during gonorrhea infection.

Prevalence of Gastrointestinal Parasites among Student of Nasarawa State University, Keffi Nasarawa State, Nigeria

Gastrointestinal parasites are significant agents of intestinal infection with public health implications worldwide. This study aimed to ascertain intestinal parasites among students of Nasarawa State University, Keffi, Nasarawa State. A total of 138 Stool samples were collected from students in hostels and off campus and examined using the direct wet preparation and formol-ether concentration techniques. The overall prevalence of 18.84% was recorded with a higher prevalence of gastrointestinal parasites in samples collected from male subjects (23.61%) compared to the female individuals (13.63%) however, there was no statically significant difference (P&gt;0.05) in prevalence between males and females subjects. The intestinal parasites species identified and their respective prevalence were: two species of nematodes; hookworm (26.92%) and Ascaris lumbricoides (46.15), a species of cestode- Taenia saginata (15.38%) and trematode- Schistosoma mansoni (11.58%). Gastrointestinal parasitic infection was higher in male hostel (50.00%) followed by female hostel (13.46%) and the least was recorded from the student village that is those students who live off campus (11.58%) although statistically, there is no significant difference between the location (P&gt;0.05). The study showed that there is a high prevalence of gastrointestinal parasites in the study area (especially male hostel) therefore, there is a need to encourage adequate personal hygiene and sanitation. Also, further study should be carried out on the impact of parasitic infection on academic performance of the students.

Study of microbiological activity of topical antibacterial agents for treatment of combat injuries

The problems of combat injuries are determined by the issue of treatment of purulent complications, because wounds received during combat operations are usually infected, and the most serious complication of such wounds is the development of purulent infection. Objective — to study the features of the aerobic component of combat wounds, the sensitivity of causative agents of wound infection to antibacterial drugs, and the antimicrobial activity of individual drugs in relation to extensively resistant and polyresistant microbial agents in order to develop external therapy algorithms as part of the complex treatment of these injuries. Materials and methods. The data of microbiological studies of patients with combat wounds were used in the work. Results and discussion. Based on the results of monitoring causative agents of purulent­inflammatory complications of wound injuries, a range of leading types of microorganisms was revealed. The isolation of flora resistant to most antibiotics from wounds dictates the need to change the strategy of infection control with strengthening measures to prevent nosocomial transmission, which should be considered when prescribing antibiotic therapy. Conclusions. Based on the results of monitoring the causative agents of purulent-inflammatory complications of wound injuries, a range of leading types of microorganisms was revealed: K. pneumoniae, E. faecalis, S. haemolyticus, P. aeruginosa, E. coli. The dominant microorganisms (by isolation frequency) in the wound contents were: staphylococci (3.0—5.69 lg CFU/ml), enterobacteria (4.69—7.0 lg CFU/ml), enterococci (3.0—4.69 lg CFU/ml). In addition, aerobic bacilli (3.0—3.69 lg CFU/g) and pseudomonads (5.69—7.0 lg CFU/g) were determined in the wound contents, which did not have a dominant character.The use of a topical agent containing dioxidin can contribute to the improvement of the effectiveness of the local treatment of purulent wounds infected with strains of gram-negative bacteria, in particular E. coli, K. pneumoniae and P. aeruginosa, with poly and extensive resistance to antibiotics both in monocultures and in microbial associations, in particular with strains of S. aureus, including MRSA.

Anti-Biofilm Perspectives of Propolis against Staphylococcus epidermidis Infections.

Staphylococcus epidermis has emerged as the main causative agent of medical device-related infections. Their major pathogenicity factor lies in its ability to adhere to surfaces and proliferate into biofilms, which increase their resistance to antibiotics. The main objective of this study was to evaluate the use and the mechanism of action of an ethanolic extract of Spanish propolis (EESP) as a potential alternative for preventing biofilm-related infections caused by S. epidermidis. The chemical composition of propolis is reported and its antibacterial activity against several strains of S. epidermidis with different biofilm-forming capacities evaluated. The influence of sub-inhibitory concentrations (sub-MICs) of EESP on their growth, physicochemical surface properties, adherence, and biofilm formation were studied. EESP interferes with planktonic cells, homogenizing their physicochemical surface properties and introducing a significant delay in their growth. The adherence and biofilms at the EESP concentrations investigated were decreased up to 90.5% among the strains. Microscopic analysis indicated that the planktonic cells that survived the treatment were the ones that adhere and proliferate on the surfaces. The results obtained suggest that the EESP has a high potential to be used as an inhibitor of both the adhesion and biofilm formation of S. epidermidis.

Rehmmannia glutinosa polysaccharide exerts antiviral activity against pseudorabies virus and antioxidant activity

Pseudorabies virus (PRV) is an important pathogen harming the global pig industry. Vaccines available for swine cannot protect against PRV completely. Furthermore, no antiviral drugs are available to treat PRV infections. Rehmmannia glutinosa polysaccharide (RGP) possesses several medicinal properties. However, its antiviral activity is not reported. In the present study, we found that RGP can inhibit PRV/XJ5 infection by western blotting, immunofluorescent assay (IFA), and TCID50 assay quantitative polymerase chain reaction (qPCR). We revealed RGP can inhibit virus adsorption and invasion into PK-15 cells in a dose-dependent manner via western blotting, IFA, TCID50 assay, and quantitative polymerase chain reaction (qPCR), and suppressed PRV/XJ5 replication through western blotting, and qPCR. Additionally, it also reduced PRV/XJ5-induced ROS, lipid oxidation, and improved SOD levels in PK-15 cells, which was observed by using corresponding test kits. To conclude, our findings suggest that RGP might be a novel therapeutic agent for preventing and controlling PRV infection and antioxidant agent.

Investigating the Effectiveness of Ceragenins against Acinetobacter baumannii to Develop New Antimicrobial and Anti-Adhesive Strategies.

A growing body of experimental data indicates that ceragenins (CSAs), which mimic the physicochemical properties of the host's cationic antimicrobial peptide, hold promise for the development of a new group of broad-spectrum antimicrobials. Here, using a set of in vivo experiments, we assessed the potential of ceragenins in the eradication of an important etiological agent of nosocomial infections, Acinetobacter baumannii. Assessment of the bactericidal effect of ceragenins CSA-13, CSA-44, and CSA-131 on clinical isolates of A. baumannii (n = 65) and their effectiveness against bacterial cells embedded in the biofilm matrix after biofilm growth on abiotic surfaces showed a strong bactericidal effect of the tested molecules regardless of bacterial growth pattern. AFM assessment of bacterial cell topography, bacterial cell stiffness, and adhesion showed significant membrane breakdown and rheological changes, indicating the ability of ceragenins to target surface structures of A. baumannii cells. In the cell culture of A549 lung epithelial cells, ceragenin CSA-13 had the ability to inhibit bacterial adhesion to host cells, suggesting that it interferes with the mechanism of bacterial cell invasion. These findings highlight the potential of ceragenins as therapeutic agents in the development of antimicrobial strategies against bacterial infections caused by A. baumannii.

Discovery and Optimization of Novel SaFabI Inhibitors as Specific Therapeutic Agents for MRSA Infection.

As the rate-limiting enzyme in fatty acid biosynthesis, Staphylococcus aureus enoyl-acyl carrier protein reductase (SaFabI) emerges as a compelling target for combating methicillin-resistant S. aureus (MRSA) infections. Herein, compound 1, featuring a 4-(1H-benzo[d]imidazol-2-yl)pyrrolidin-2-one scaffold, was identified as a potent SaFabI inhibitor (IC50 = 976.8 nM) from an in-house library. Subsequent optimization yielded compound n31, with improved inhibitory efficacy on enzymatic activity (IC50 = 174.2 nM) and selective potency against S. aureus (MIC = 1-2 μg/mL). Mechanistically, n31 directly inhibited SaFabI in cellular contexts. Moreover, n31 exhibited favorable safety and pharmacokinetic profiles, and dose-dependently treated MRSA-induced skin infections, outperforming the approved drug, linezolid. The chiral separation of n31 resulted in (S)-n31, with superior activities (IC50 = 94.0 nM, MIC = 0.25-1 μg/mL) and in vivo therapeutic efficacy. In brief, our research proposes (S)-n31 as a promising candidate for SaFabI-targeted therapy, offering specific anti-S. aureus efficacy and potential for further development.

Обзор эффективности и безопасности препарата Канефрон® Н при лечении и профилактике инфекций мочевыводящих путей у различных групп пациентов.

Introduction. The growth of antibiotic-resistant strains of microorganisms that cause urological infections, especially uropathogenic Escherichia coli, the main causative agent of uncomplicated urinary tract infections, requires the search for alternative antimicrobial treatment methods. The discovery of the urine microbiome explains the concept of «asymptomatic bacteriuria», which in most cases does not require the use of antibiotics. The effectiveness of herbal preparations in the treatment and prevention of urinary tract infections has been proven by their traditional use over many years, as well as by scientific research in recent decades. Materials and methods. The presented review summarizes the results of the use of the drug Canephron® N over the past decade, published in the international databases PubMed, Embase, Cochrane Library, ClinicalTrials.gov, articles in Russian from the eLibrary.ru database and their bibliography. Data from randomized, observational clinical studies in adult patients and children are presented. The studies were conducted in patients with infectious and inflammatory diseases of the kidneys, bladder and urinary tract. Results. 32 publications in both Russian and English were analyzed. Publications are grouped together: the use of Canephron® N in the treatment and prevention of urinary tract infections (cystitis and pyelonephritis) in adults; in children; in pregnant women; after urological interventions. The quality of the studies and side effects after using Canephron® N were discussed. Conclusions. The effectiveness and safety of Canephron® N in the treatment and prevention of urological diseases has been proven.

Candida parapsilosis: Heterogeneous and strain-specific expression of secreted aspartic proteases (Sapp1 and Sapp2).

The increasing prevalence of Candida parapsilosis as a causative agent of fungal infections underscores the need to comprehensively understand its virulence factors. Secreted aspartic proteases (Saps) play a significant role in adhesion events, promoting biofilm formation, causing tissue damage and evading the host's immune response. In C. parapsilosis, three Saps have been identified: Sapp1, Sapp2 and Sapp3. The present study investigates the production dynamics of Sapp1 and Sapp2 across 10 clinical isolates of C. parapsilosis using various approaches. Each fungal isolate demonstrated the capability to utilize bovine serum albumin (BSA) as the sole nitrogen source, as evidenced by its degradation in a cell-free culture medium, forming low molecular mass polypeptides. Interestingly, the degradation of different proteinaceous substrates, such as BSA, human serum albumin (HSA), gelatin and hemoglobin, was typically isolate-dependent. Notably, higher proteolysis of HSA compared to BSA, gelatin and hemoglobin was observed. A quantitative assay revealed that the cleavage of a peptide fluorogenic substrate (cathepsin D) was isolate-specific, ranging from 44.15 to 270.61 fluorescence arbitrary units (FAU), with a mean proteolysis of 150.7 FAU. The presence of both Sapp1 and Sapp2 antigens on the cell surface of these fungal isolates was confirmed through immunological detection employing specific anti-Sapp1 and anti-Sapp2 antibodies. The surface levels of Sapp1 were consistently higher, up to fourfold, compared to Sapp2. Similarly, higher levels of Sapp1 than Sapp2 were detected in fungal secretions. This study provides insights into the dynamic expression and regulation of Sapps in C. parapsilosis, highlighting a known virulence factor that is considered a potential target for drug development against this increasingly prominent pathogen.

Innovative Design Strategy and Research Progress of Anti Human Papilloma Virus Infection Agents

This review summarized the mechanism of a novel fusion protein (PHPV fusion protein) containing membrane penetrating peptide and oligopeptide-1 (EGF). The new PHPV fusion protein contains two kinds of polypeptides: membrane penetrating peptide and oligopeptide-1, so it has a good function of preventing and treating HPV virus. PHPV fusion protein not only has the multi effect function of membrane penetrating peptide and oligopeptide-1, but also the negative charge (anion) C-terminal of the cross-linked and fused new protein surface interacts with the positive charge (cation) N-terminal on HPV particles. Through the combination of the N-terminal of the positive charge on its surface with the negative charge of the hydrophobic region in the middle and the C-terminal of the recognition region site containing peptidase, the membrane translocation signal is coupled with the NLS of the nuclear localization signal, thus blocking the invasion of human papillomavirus into host cells. Through the interaction of cell membrane, it can penetrate the natural barrier of cell membrane and play a role in destroying the viral membrane shell to inactivate the virus, so as to prevent cervical precancerous lesions and treat HPV infection. PHPV fusion protein can repair damaged cells, enhance the elasticity of loose vaginal mucosa, tighten the inner wall of the vagina, improve the vaginal wetness, and reduce the vaginitis reaction.

Lameness in Cattle-Etiopathogenesis, Prevention and Treatment.

The aim of this review was to analyse the health problem of lameness in dairy cows by assessing the health and economic losses. This review also presents in detail the etiopathogenesis of lameness in dairy cattle and examples of its treatment and prevention. This work is based on a review of available publications. In selecting articles for the manuscript, the authors focused on issues observed in cattle herds during their clinical work. Lameness in dairy cattle is a serious health and economic problem around the world. Production losses result from reduced milk yield, reduced feed intake, reproductive disorders, treatment costs, and costs associated with early culling. A significant difficulty in the control and treatment of lameness is the multifactorial nature of the disease; causes may be individual or species-specific and may be associated with the environment, nutrition, or the presence of concomitant diseases. An important role is ascribed to infectious agents of both systemic and local infections, which can cause problems with movement in animals. It is also worth noting the long treatment process, which can last up to several months, thus significantly affecting yield and production. Given the high economic losses resulting from lameness in dairy cows, reaching even >40% (depending on the scale of production), there seems to be a need to implement extensive preventive measures to reduce the occurrence of limb infections in animals. The most important effective preventive measures to reduce the occurrence of limb diseases with symptoms of lameness are periodic hoof examinations and correction, nutritional control, and bathing with disinfectants. A clean and dry environment for cows should also be a priority.