Etiologic Agent Research Articles

Overview of viral meningitis in the state of Pernambuco: An epidemiological analysis

Meningitis is an infectious disease, characterized by an inflammatory process of the meninges, which are membranes that surround the brain and spinal cord, acting to protect the central nervous system. The objective of the present study was to analyze and recognize the panorama of viral hospitalizations in the state of Pernambuco, as well as diagnosis, treatment and prevention. The study is an epidemiological, cross-sectional, descriptive and quantitative study. The data presented are notifications of viral meningitis in the state of Pernambuco, from January 2013 to December 2022. The state of Pernambuco recorded 4,670 cases of viral meningitis from 2013 to 2022. Of these, 59.6% were from male, with the most affected cities being: Recife (99.2%) and Limoeiro (0.25%). The most affected age group was 01 to 04 years old (25.9%) with 1,210 cases, followed by the 05 to 09 years old group with 1,187 cases and 40-59 years old with 640 cases. Regarding clinical evolution, a higher percentage cure rate was noted (94.66%). In the literature, there is a Brazilian prevalence of meningitis in males, corroborating the study, and in boys up to 9 years of age, viral meningitis was more common. The data presented here is relevant. Even with the existence of immunization offered free of charge by the Unified Health System for the most common etiological agents of meningitis, cases in Pernambuco continue to occur.

Mucosal bivalent live attenuated vaccine protects against human metapneumovirus and respiratory syncytial virus in mice

Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses. Altogether, our results showed the versatility of the Metavac® platform and suggested that Metavac®-RSV is a promising mucosal bivalent LAV candidate to prevent pneumovirus-induced diseases.

Virus-Induced MicroRNA Modulation and Systemic Sclerosis Disease.

MicroRNAs (miRNAs) are short noncoding RNA sequences that regulate gene expression at the post-transcriptional level. They are involved in the regulation of multiple pathways, related to both physiological and pathological conditions, including autoimmune diseases, such as Systemic Sclerosis (SSc). Specifically, SSc is recognized as a complex and multifactorial disease, characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis, affecting skin and internal organs. Among predisposing environmental triggers, evidence supports the roles of oxidative stress, chemical agents, and viral infections, mostly related to those sustained by beta-herpesviruses such as HCMV and HHV-6. Dysregulated levels of miRNA expression have been found in SSc patients compared to healthy controls, at both the intra- and extracellular levels, providing a sort of miRNA signature of the SSc disease. Notably, HCMV/HHV-6 viral infections were shown to modulate the miRNA profile, often superposing that observed in SSc, potentially promoting pathological pathways associated with SSc development. This review summarizes the main data regarding miRNA alterations in SSc disease, highlighting their potential as prognostic or diagnostic markers for SSc disease, and the impact of the putative SSc etiological agents on miRNA modulation.

Association between KSHV-Specific Humoral and T Cell Responses with Recurrence of HIV-Associated Kaposi Sarcoma.

Kaposi sarcoma (KS) is an AIDS-defining angio-proliferative malignancy, with the Kaposi sarcoma-associated herpes virus (KSHV) as its etiologic agent. Upon treatment with chemotherapy, a proportion of HIV-associated KS patients experience disease recurrence within a few months of completing treatment. We aimed at determining whether KSHV-specific adaptive immune responses were associated with KS recurrence upon complete remission. We conducted a prospective cohort study. The primary outcome was the recurrence of HIV-associated KS. An immunofluorescence assay was used to determine anti-KSHV antibodies, an enzyme-linked immunospot was conducted for T cell responses, PCR was carried out to determine KSHV status, and flow cytometry was used for CD4 counting and immunophenotyping. KSHV detection in PBMCs was high and not associated with KS recurrence-free survival (p = 0.29). Anti-KSHV antibody titers were high and not associated with recurrence-free survival (p = 0.63). KSHV-specific T cell responses dropped from baseline levels among individuals with recurrence, but the drop was not statistically significant. Individuals experiencing KS recurrence had a significantly higher proportion of T cell subsets expressing PD1, while those with sustained remission had a significant increase in CD4 T cell counts from baseline levels during the follow-up period (p = 0.02). Anti-KSHV antibodies are not a good correlate of protection from KS recurrence. T cells in individuals experiencing KS recurrence hadhigh PD1 expression, while an increase in CD4 counts was associated with sustained KS remission.

A retrospective investigation of the population structure and geospatial distribution of Salmonella Paratyphi A in Kathmandu, Nepal.

Salmonella Paratyphi A, one of the major etiologic agents of enteric fever, has increased in prevalence in recent decades in certain endemic regions in comparison to S. Typhi, the most prevalent cause of enteric fever. Despite this increase, data on the prevalence and molecular epidemiology of S. Paratyphi A remain generally scarce. Here, we analysed the whole genome sequences of 216 S. Paratyphi A isolates originating from Kathmandu, Nepal between 2005 and 2014, of which 200 were from patients with acute enteric fever and 16 from the gallbladder of people with suspected chronic carriage. By exploiting the recently developed genotyping framework for S. Paratyphi A (Paratype), we identified several genotypes circulating in Kathmandu. Notably, we observed an unusual clonal expansion of genotype 2.4.3 over a four-year period that spread geographically and systematically replaced other genotypes. This rapid genotype replacement is hypothesised to have been driven by both reduced susceptibility to fluoroquinolones and genetic changes to virulence factors, such as functional and structural genes encoding the type 3 secretion systems. Finally, we show that person-to-person is likely the most common mode of transmission and chronic carriers seem to play a limited role in maintaining disease circulation.

Fibropapillomatosis: A Review of the Disease with Attention to the Situation Northern Coast of Brazil.

Fibropapillomatosis in sea turtles is a potentially debilitating and fatal disease for which there is still a lack of knowledge, especially for specific regions of Brazil. The diagnosis is made through the observation of clinical manifestations, and despite its association with Chelonid Alphaherpesvirus 5 (ChHV5) as the etiological agent, the expression of the disease may also be related to immunological and environmental factors caused by anthropic degradation of the environment. Thus, this review aims to elucidate what is known about this disease globally, and especially in various regions of Brazil, promoting a better understanding of its evolution, spatiotemporal prevalence, and relationship with human activities. Furthermore, the review explores the molecular biology of ChHV5, including its genomic structure, replication cycle, and mechanisms of pathogenesis. The role of environmental factors, such as temperature and pollution, in modulating ChHV5 infection and FP development is also discussed. Additionally, the review summarizes current diagnostic methods for detecting ChHV5 infection in sea turtles, highlighting the importance of early detection and monitoring for effective disease management and conservation efforts. Finally, the review outlines future research directions aimed at improving our understanding of ChHV5 and developing strategies for FP control and prevention in sea turtle populations.

Maternal consumption of fish oil protected breast-fed piglets against Escherichia coli lipopolysaccharide-induced damage through reshaping of intestinal fatty acids profile.

It has been well documented that n-3 polyunsaturated fatty acids (n-3 PUFA) can alleviate inflammation caused by Escherichia coli (E. coli) lipopolysaccharides (LPS), the etiologic agents that causing yellow or white dysentery in young pigs. However, it remains unclear whether the increase in n-3 PUFA availability could enhance the ability of nursery pigs to resist invasion by E. coli. LPS. Twenty-four 21-day-old female piglets, each two of them from the same sow fed the beef tallow (BT) or fish oil (FO) diets, were allocated into four treatment groups: BT-CON, piglets from the BT-fed sows and intraperitoneally injected with saline (9 g/L); BT-LPS, piglets from the BT-fed sows and injected with LPS (100 μg/kg body weight); FO-CON, piglets from the FO-fed sows and injected with saline; FO-LPS, piglets from the FO-fed sows and injected with LPS. Following 2 h of LPS challenge, the magnitudes of increase in body temperature approached to a marked (p < 0.01) difference between the BT-CON and BT-LPS piglets, whereas the dramatic (p < 0.01) difference between the FO-CON and FO-LPS piglets was only observed at 4 h post LPS challenge. The body temperature averaged across the time points evaluated was about 0.2°C lower (p < 0.05) in the FO group than in the BT group. The FO group had lower (p < 0.05) mean corpuscular hemoglobin concentration, lower increase in serum interleukin (IL)-1β (p < 0.10) and IL-8 (p < 0.05) levels, higher (p < 0.01) serum albumin concentration, and higher (p = 0.10) ratios of jejunum villus height to crypt depth than the BT group. The FO group had much higher (p < 0.0001) ileal content of C20:5n3, C24:0, and C22:6n3, which were 2-4 times the content of the BT group. LPS challenge resulted in decreased (p < 0.05) intestinal C20:1 and C20:5n3 content, and the decrease (p < 0.05) in intestinal C20:3n6 and C24:1 content was observed in the BT-LPS piglets rather than in the FO-LPS piglets. Taken together, this study indicated that maternal consumption of fish oil protected breast-fed piglets against E. coli LPS-induced damage through reshaping of intestinal fatty acids profile, which sheds new light on the development of nutritional strategies to enhance the ability of young pigs to resist E. coli invasion.

The results of epidemiological analysis of salmonellosis incidence in the Rostov region under current conditions

Objective: to study the features of the epidemic process of salmonella infection under current conditions. To establish a causal relationship between the incidence of salmonellosis and the functioning of public catering enterprises, which can form the epidemiological risks.Materials and methods: to assess the intensity, dynamics and structure of the epidemic process of salmonella infection, methods of operative and retrospective epidemiological analysis used, to identify and characterize etiological agents — laboratory methods: bacteriological, serological, molecular genetic analysis.Results: in the course of the study, the epidemiological features of the spread of salmonellosis in the Rostov region were established, the main risks which can form multiple foci were determined on the example of a specific epidemic situation: the possible source of infection, pathways and transmission factors, the etiological agent — Salmonella enteritidis gr. O:9 (D1). Gross violations of sanitary legislation in organizing the work of a public catering enterprise caused a wide contamination of finished culinary goods by pathogens of salmonella infection.Conclusion: based on the identified features of the epidemic process, a complex of measures developed; the focus of infection localized and eliminated. Recommendations for the prevention of salmonellosis for workers in objects of a similar profile and the population are given.

Deferral of blood donors who have ever stayed in a Trypanosoma cruzi endemic area: An international survey.

Trypanosoma cruzi is the etiologic agent of Chagas disease (CD), an anthropozoonosis from the American continent that progresses from an acute phase to an indeterminate phase, followed by a chronic symptomatic phase in around 30% of patients. In countries where T. cruzi is not endemic, many blood transfusion services test blood donors who have stayed in an endemic country ('at-risk stay')-even if they do not present with other risk factors. However, the efficiency of this approach has been questioned. On 18 September 2023, a worldwide survey was distributed among employees of blood transfusion services. The questions mainly pertained to CD's endemicity in the blood services' region, the current testing policy for T. cruzi and the number of confirmed positive results among donors with a prior at-risk stay alone (i.e., without other risk factors for T. cruzi infection). Twenty-six recipients completed the survey. Of the 22 (84.6%) blood services that operated in a non-endemic region, 9 (42.9%) tested donors for T. cruzi, including 8 (88.9%) that considered the travel history or the duration of the stay (alone) in their testing algorithm ('study blood services'). Over 93 years of observation among all study blood services, 2 donations from donors with an at-risk stay alone and 299 from those with other risk factors were confirmed positive for T. cruzi. The study findings question the utility of testing blood donors who have stayed in an endemic country without other risk factors.

Epidemiology of Tinea Capitis Among School-Children in Dschang, Western Cameroon.

Data on the epidemiology of tinea capitis (TC), an infection of the scalp by dermatophytes, are scarce in Cameroon. This study aimed to determine the prevalence of TC among school-children in the Dschang Subdivision, Western Cameroon. A cross-sectional study was carried out in June 2021 in Dschang including pupils aged 5-13. First, a standardized questionnaire was administered to participant for the collection of sociodemographic data. Then, samples were collected and cultured onto Sabouraud-Chloramphenicol-Gentamicin Agar. The etiological agents were identified based on their morphological features and with MALDI-TOF mass spectrometry. A total of 1070 children were clinically examined and 108 (10.1%) children presented with TC lesions. The mean age of the 1070 participants was 8.3 ± 2.6years (range: 5-13years); 772 (72.2%) were males. The use of borehole water (OR = 0.01, 95%CI[0.001-0.03]), spring water (OR = 0.2, 95%CI[0.08-0.50]), rainwater (OR = 0.004, 95%CI[0.001-0.016]), and hairdressing salons visits (OR = 0.413, 95%CI[0.196-0.872]) were associated with a decreased TC risk in the multivariate logistic regression analysis. In contrast, sharing bed with siblings (OR = 4.48, 95%CI[2.095-9.60]) was associated with an increased TC risk in children. Among the 32 dermatophytes isolated in culture, Microsporum audouinii was the most frequent (43.8%), followed by Trichophyton rubrum (25.0%) and T. soudanense (25.0%). Microsporum canis and T. violaceum were both rarely isolated. Further studies are warranted to assess the association of TC with domestic water usage that has been highlighted in this study.

Mucositis y exantema, ¿qué hay de nuevo? Erupción mucocutánea infecciosa reactiva

Reactive infectious mucocutaneous eruption (RIME) is a recently emerged term that describes cases of post-infectious mucositis associated with different etiological agents (viral and bacterial). It is part of the spectrum of Stevens-Johnson syndrome (SSJ) / toxic epidermal necrolysis (NET), although it presents with milder symptoms, with predominantly mucosal involvement. Treatment consists of supportive measures, and may include targeted antibiotic therapy and systemic corticosteroid therapy in cases with extensive involvement.

Antifungal efficacy and immunomodulatory effect of PLGA nanoparticle-encapsulated itraconazole in histoplasmosis in vivo model

IntroductionHistoplasma capsulatum is the etiological agent of histoplasmosis, the most common endemic pulmonary mycosis. Itraconazole (ITZ) is the choice for mild disease and a step-down therapy in severe and disseminated clinical presentations. Drug encapsulation into nanoparticles (NPs) is an alternative to improve drug solubility and bioavailability, reducing undesirable interactions and drug degradation and reaching the specific therapeutic target with lower doses. Objectiveevaluate the antifungal and immunomodulatory effect of ITZ encapsulated into poly(lactic-co-glycolic acid) (PLGA) NPs, administrated orally and intraperitoneally in an in vivo histoplasmosis model. ResultsAfter intranasal infection and treatment of animals with encapsulated ITZ by intraperitoneal and oral route, fungal burden control, biodistribution, immune response, and histopathology were evaluated. The results showed that the intraperitoneal administered and encapsulated ITZ has an effective antifungal effect, significantly reducing the Colony-Forming-Units (CFU) after the first doses and controlling the infection dissemination, with a higher concentration in the liver, spleen, and lung compared to the oral treatment. In addition, it produced a substantial immunomodulatory effect on pro- and anti-inflammatory cytokines and immune cell infiltrates confirmed by histopathology. ConclusionsOverall, results suggest a synergistic effect of the encapsulated drug and the immunomodulatory effect contributing to infection control, preventing their dissemination.

Investigating the importance of selected surface-exposed loops in HpuB for hemoglobin binding and utilization by Neisseria gonorrhoeae.

Neisseria gonorrhoeae is the etiological agent of the sexually transmitted infection gonorrhea. The pathogen is a global health challenge since no protective immunity results from infection, and far fewer treatment options are available with increasing antimicrobial resistance. With no efficacious vaccines, researchers are exploring new targets for vaccine development and innovative therapeutics. The outer membrane TonB-dependent transporters (TdTs) produced by N. gonorrhoeae are considered promising vaccine antigens as they are highly conserved and play crucial roles in overcoming nutritional immunity. One of these TdTs is part of the hemoglobin transport system comprised of HpuA and HpuB. This system allows N. gonorrhoeae to acquire iron from hemoglobin (hHb). In the current study, mutations in the hpuB gene were generated to better understand the structure-function relationships in HpuB. This study is one of the first to demonstrate that N. gonorrhoeae can bind to and utilize hemoglobin produced by animals other than humans. This study also determined that when HpuA is absent, mutations targeting extracellular loop 7 of HpuB led to defective hHb binding and utilization. However, when the lipoprotein HpuA is present, these loop 7 mutants recovered their ability to bind hHb, although the growth phenotype remained significantly impaired. Interestingly, loop 7 contains putative heme-binding motifs and a hypothetical α-helical region, both of which may be important for the use of hHb. Taken together, these results highlight the importance of loop 7 in the functionality of HpuB in binding hHb and extracting and internalizing iron.

Investigation of the presence of Chlamydia spp., Mycoplasma spp. and Moraxella ovis in infectious keratoconjunctivitis cases in sheep and goats in Siirt province and evaluation of clinical findings

Infectious keratoconjunctivitis is an infectious disease that negatively affects animal welfare causing systemic or local clinical signs in small ruminants and causes significant economic losses in herds. It is important to determine the etiologic agent causing the infection in the development of the protection and control strategies against the disease. The aim of this study was to determine the presence of infectious keratoconjunctivitis cases in small ruminants raised in Siirt province in Türkiye. Infectious keratoconjunctivitis was graded according to the symptoms determined by clinical examination. The presence of Chlamydia spp., Mycoplasma spp. and Moraxella ovis was investigated by PCR in swab samples obtained from the animals with keratoconjunctivitis. Infectious keratoconjunctivitis was detected in 263 (19.86%) of 1324 animals examined in the study. Of the animals with infectious keratoconjunctivitis, 163 (61.97%) were sheep and 100 (38.02%) were goats. The detection rate of infectious keratoconjunctivitis was higher in sheep than goats. In 56 (21.29%), 109 (41.44%), 67 (25.47%), and 31 (11.78%) of the cases, findings of stage 1, 2, 3, and 4 infectious keratoconjunctivitis were detected, respectively. Of the eye swab samples taken from 263 animals with infectious keratoconjunctivitis, 5 (1.90%) were positive for Mycoplasma spp. and 6 (2.28%) were positive for M. ovis. It was determined that the distribution of the bacterial agents varied according to the stage of infectious keratoconjunctivitis. No statistically significant correlation was found in the distribution of bacterial agents among identified samples according to species, sex, age, and infectious keratoconjunctivitis stage of the animals. It was thought that the data obtained in the study would contribute to the studies for protection and control by determining the incidence and aetiology of infectious keratoconjunctivitis cases observed in small ruminants.

Key aspects of papillomavirus infection influence the host cervicovaginal microbiome in a preclinical murine papillomavirus (MmuPV1) infection model.

Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female FVB/N mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.IMPORTANCEHuman papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.

Imiquimod Reverses Chronic Toxoplasmosis-Associated Behavioral and Neurocognitive Anomalies in a Rat Model.

Toxoplasma gondii is the etiologic agent of toxoplasmosis, a highly prevalent parasitosis. Toxoplasma gondii (T. gondii) transits in the brain from acute (AT) to chronic toxoplasmosis (CT), under host immune control. In immunocompromised patients, reactivation of CT is potentially life-threatening. Behavioral and neurological complications have been associated with CT. Furthermore, an effective treatment targeting CT is still lacking. We previously reported the efficacy of imiquimod against CT. Here, we demonstrate the molecular effects of imiquimod or imiquimod followed by the clinically used combination of sulfadiazine and pyrimethamine (SDZ + PYR) on CT-associated behavior in a rat model. Imiquimod decreased the number of cysts in the brains of chronically infected rats due to an induced reactivation of bradyzoites into tachyzoites. Importantly, this decrease was more pronounced in rats treated with imiquimod followed by SDZ + PYR. Rats chronically infected with T. gondii exhibited an anxiety-like behavior. Notably, treatment with imiquimod reversed this behavior aberrancy, with even a more pronounced effect with imiquimod followed by SDZ/PYR. Similarly, rats chronically infected with T. gondii exhibited learning deficits, and imiquimod alone or followed by SDZ/PYR reversed this behavior. Our results enhance our knowledge of the implications of CT on behavioral aberrancies and highlight the potency of imiquimod followed by SDZ + PYR on these CT-associated complications.

Spectrum of Lower Respiratory Bacterial Pathogens and their Antimicrobial Susceptibility in a Tertiary Care Hospital at Rawalpindi

Objective: To study the spectrum of bacterial etiological agents causing lower respiratory tract infections and their antimicrobial susceptibility pattern in a tertiary care hospital at Rawalpindi. Methodology: A descriptive, cross-sectional study was conducted in the department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from June to December 2021. Total 130 patients with lower respiratory tract infections (LRTIs) irrespective of age and gender were included in the study while patients of pulmonary tuberculosis, fungal diseases and patients having prior antibiotic therapy before sample collection were excluded. Non quantitative cultures were performed for sputum, non- directed bronchial lavage (NBL), pleural fluid and quantitative cultures for bronchoalveolar lavage (BAL) and endobronchial (EB) washings specimens. Antibiotic susceptibility was performed using Clinical and Laboratory Standards Institute (CLSI) 2021 guidelines. Results: Pseudomonas aeruginosa (26.9%) was found to be the most prevalent bacterial pathogen followed by Klebsiella pneumoniae (23%). Both Gram negative and Gram-positive bacteria showed highest antimicrobial resistance to flouroquinolones. Gram negative bacteria were more susceptible to aminoglycosides and carbapenems. Gram positive bacteria were most susceptible to linezolid and vancomycin. Staphylococcus aureus was isolated from 8 samples, of which 5(62.5%) were Methicillin-resistant Staphylococcus aureus (MRSA). Conclusion: This study concluded that the most frequent bacterial pathogen causing lower respiratory tract infections was Pseudomonas aeruginosa and both Gram negative and Gram-positive bacteria showed highest antimicrobial resistance to flouroquinolones.

Multi-Etiological Abortion due to Campylobacter spp. and Chlamydia abortus in a Sheep

In this case, multi-etiologic abortion due to Campylobacter spp. and Chlamydia abortus was determined in an aborted sheep fetus sent to Konya Veterinary Control Institute (KVKE) from a sheep farm operating in Aksaray province in 2020. The presence of Campylobacter spp. was determined by the bacterial isolation method. C.abortus was identified by qPCR and immunohistochemistry (IHC) methods. This study should be published in order to emphasize that in the fight against sheep abortions, multi-etiologic abortions involving multiple agents should be taken into consideration in addition to a single etiologic agent, and a multidisciplinary approach should be used in the diagnosis to identify the abortion agents.

Molecular characterization and virulence factor profiles of Staphylococcus aureus isolated from bovine mastitis in Brazilian herds

Staphylococcus aureus is the main etiological agent of bovine mastitis worldwide and knowledge about its diversity and virulence factors is vital in controlling infections caused by this pathogen. The present study aimed to perform molecular characterization of a population of S. aureus (n=153 strains isolated from 1994 to 2014 in seven Brazilian states) by pulsed-field gel electrophoresis (PFGE) and evaluate their virulence profiles via polymerase chain reaction (PCR). PFGE identified 93 pulsotypes, with the isolates organized into 26 clusters and 20 unique pulsotypes. Predominant pulsotypes were observed, with variations according to the years of isolation and geographic origin of the isolates. Based on the PCR results for the genes encoding agglutination factors (ClfA and ClfB), binding proteins (fibronectin binding protein - FnBPA, elastin binding protein - Ebps, collagen binding protein - Cna), and toxins (Hla, Hlb and Luk-ED), 40 virulence profiles were detected. The frequency of virulence genes ranged from 58 to 98% (clfA:84.3%; clfB and hlb both 81%; hla:71.2%; fnBA:82.3%; Can:94.7%; ebps:58%; and lukED:98%). The existence of prevalent genotypes in some of the Brazilian states and the time period studied suggests that these genotypes are better adapted, with favorable characteristics in host/pathogen relationships. Genes of proven importance for S. aureus pathogenesis in bovine mastitis were widely distributed in genetically divergent populations, suggesting that most of these genes may be interesting candidates in the development of vaccines to control bovine mastitis in Brazil.

Identification of a copper-responsive small molecule inhibitor of uropathogenic Escherichia coli.

Urinary tract infections (UTIs) are a major global health problem and are caused predominantly by uropathogenic Escherichia coli (UPEC). UTIs are a leading cause of prescription antimicrobial use. Incessant increase in antimicrobial resistance in UPEC and other uropathogens poses a serious threat to the current treatment practices. Copper is an effector of nutritional immunity that impedes the growth of pathogens during infection. We hypothesized that copper would augment the toxicity of select small molecules against bacterial pathogens. We conducted a small molecule screening campaign with a library of 51,098 molecules to detect hits that inhibit a UPEC ΔtolC mutant in a copper-dependent manner. A molecule, denoted as E. coli inhibitor or ECIN, was identified as a copper-responsive inhibitor of wild-type UPEC strains. Our gene expression and metal content analysis results demonstrate that ECIN works in concert with copper to exacerbate Cu toxicity in UPEC. ECIN has a broad spectrum of activity against pathogens of medical and veterinary significance including Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Subinhibitory levels of ECIN eliminate UPEC biofilm formation. Transcriptome analysis of UPEC treated with ECIN reveals induction of multiple stress response systems. Furthermore, we demonstrate that L-cysteine rescues the growth of UPEC exposed to ECIN. In summary, we report the identification and characterization of a novel copper-responsive small molecule inhibitor of UPEC.IMPORTANCEUrinary tract infection (UTI) is a ubiquitous infectious condition affecting millions of people annually. Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of UTI. However, UTIs are becoming increasingly difficult to resolve with antimicrobials due to increased antimicrobial resistance in UPEC and other uropathogens. Here, we report the identification and characterization of a novel copper-responsive small molecule inhibitor of UPEC. In addition to E. coli, this small molecule also inhibits pathogens of medical and veterinary significance including Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus.