Comparative pathogenicity of Nocardia seriolae in Nile tilapia (Oreochromis niloticus), milkfish (Chanos chanos) and Asian seabass (Lates calcarifer).

Nocardiosis, caused by Nocardia seriolae, has been a prominent disease in Southeast Asian aquaculture in the last three decades. This granulomatous disease reported in various fish species is responsible for significant economic losses. This study investigated the pathogenicity of N. seriolae in three cultured species in Taiwan: Nile tilapia (omnivore), milkfish (herbivore) and Asian seabass (carnivore). Administration of an infective dose of 1 × 106 CFU/ fish in tilapia, seabass and milkfish demonstrated mortalities of 100%, 90% and 75%, respectively. Additionally, clinical signs namely, granuloma and lesions displayed varying intensities between the groups and pathological scores. Polymerase chain reaction (PCR) amplification specific for N. seriolae was confirmed to be positive (432 bp) using NS1/NG1 primers. Post-mortem lesions revealed the absence of granulomas in tilapia and milkfish and their presence in the seabass. Interestingly, the gut in tilapia showed an influx of eosinophils suggesting its role during the acute stages of infection. However, post-challenge, surviving milkfish exhibited granulomatous formations, while surviving seabass progressed toward healing and tissue repair within sampled tissues. Overall, in conclusion, these results demonstrate the versatility in the immunological ability of individual Perciformes to contain this pathogen as a crucial factor that influences its degree of susceptibility.

Brain Abscess Caused by Nocardia: Case Report and Literature Review

Nocardia brain abscess is a rare clinical entity, accounting for 2% of all brain abscesses, associated with high morbidity and amortality rate 3 times higher than brain abscesses caused by other bacteria. Proper investigation and treatment, characterized by a longterm antibiotic therapy, play an important role on the outcome of the patient. The authors describe a case of a patient without neurological comorbidities who developed clinical signs of right occipital lobe impairment and seizures, whose investigation demonstrated brain abscess caused by Nocardia spp. The patient was treated surgically followed by antibiotic therapy with a great outcome after 1 year of follow-up.

Case report: pulmonary nocardiosis caused by Nocardia exalbida in an immunocompetent patient.

BACKGROUND: Nocardiosis is known as an opportunistic infection in immunocompromised hosts, but it occasionally has been reported in immunocompetent patient. The Nocardia exalbida is first-reported in 2006 from Japan, and a few cases of have been reported in only immunocompromised host, and the characteristic is still unclear. We herein describe the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient. CASE PRESENTATION: A77 -year-old Japanese man was admitted to our hospital on November 2, 2018. He was a lifelong non-smoker with no childhood history of respiratory disease. He had a medical history of dyslipidemia. One month before this admission fevers, sputum, mild cough were developed and he was evaluated in a clinic near our hospital. His diagnosis was community acquired pneumonia within his right middle lobe. He was treated with ceftriaxone 1 g/day intravenously for a week, however his symptoms relapsed a few days later. So, the physician retried ceftriaxone for another 3 days, but his symptoms did not improve. He was referred to our hospital. He was treated with sitafloxacin as an outpatient for a week, however his symptoms got worse. The chest CT showed consolidation and atelectasis in his right middle lobe. Low density area was scattered in consolidation, and right pleural effusion was observed. The patient was diagnosed with pulmonary abscess and he was admitted. Administration of piperacillin/tazobactam improved his condition. We switched antibiotics to amoxicillin/clavulanate, and he was discharged. After 2 weeks, he relapsed and was admitted again. After administration of piperacillin/tazobactam for 3 weeks, we perform bronchoscopy and Nocardia species were cultured from samples of the bronchial wash. The isolates were identified as N. exalbida using 16S rRNA gene sequencing. We prescribed Trimethoprim / Sulfamethoxazole (TMP/SMX) for 4 months. Then we switched to minocycline for renal dysfunction caused from TMP-SMX for 1 more month. After 5 months therapy, Consolidation on CT disappeared, and Nocardiosis was cured. CONCLUSION: we reported the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient. N. exalbida infection might be associated with a good response to treatment.

Molecular characterization and functional analysis of IL-18 in snakehead (Channa argus) during Aeromonas schubertii and Nocardia seriolae infections.

As a proinflammatory cytokine of the interleukin-1 (IL-1) family, IL-18 plays important roles in host protection against bacterial, viral, and fungal infection. We cloned the open reading frame of snakehead (Channa argus) IL-18 (shIL-18) and found that it contained 609 base pairs and encoded 202 amino acid residues. The shIL-18 included a conserved IL-1-like family signature and two potential IL-1ß-converting enzyme cutting sites; one was conserved in all analyzed IL-18s, but the other was unique to shIL-18. Unlike other IL-18s, shIL-18 also contained a predicted signal peptide. In this study, shIL-18 was constitutively expressed in all tested tissues, and its expression was induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo and by lipoteichoic acid, lipopolysaccharides, and polyinosinic-polycytidylic acid in head kidney leukocytes in vitro. Moreover, recombinant shIL-18 upregulated the expression of interferon-γ, IL-1ß, and tumor necrosis factor-α1 and -α2 and promoted the proliferation of leukocytes. Taken together, these results showed that IL-18 played crucial roles in host defense against bacterial infection in fish, as it does in mammals.

Genotypic and phenotypic prevalence of Nocardia species in Iran: First systematic review and meta-analysis of data accumulated over years 1992-2021.

BACKGROUND: Nocardia species belong to the aerobic actinomycetes group of bacteria which are gram-positive and partially acid-fast Bacilli. These bacteria may sometimes be associated with nosocomial infections. Nocardia diseases are not required to be reported to public health authorities in Iran. Hence, the present study was designed to determine the prevalence of human Nocardia spp. in Iran by using a systematic review and meta-analysis according to the preferred reporting items for systematic reviews and meta-Analyses statement. METHODS: The data of the prevalence of Nocardia species were collected from databases such as Embase, PubMed/MEDLINE via Ovid, Web of Science, Scopus and Google Scholar as well as national Iranian databases, including SID, Magiran. Analyses were conducted by STATA 14.0. RESULTS: The meta-analyses showed that the proportion of Nocardia spp. in Iranian studies varied from 1.71(1.17, 2.24) to 0.46(0.09, 0.83). N. asteroides (21% [95% CI 1.17, 2.24]), N. cyriacigeorgica (17% [95% CI 0.99, 1.77]), N. facanica (10% [95% CI 0.75, 1.00]) were considered to be common causative agents. CONCLUSIONS: Our study presents that despite the fact that Nocardia spp. are normally are saprophytic organisms, are currently accounts as emerging pathogens due to an increase in immunocompromised patients among Iranian populations. Considering our results, the establishment of advanced diagnostic facilities for the rapid detection of Nocardia infections are required for optimal therapeutic strategies of Nocardia spp. in Iran. Our findings could help the programmatic management of the disease within the context of Nocardia control programs.

Evaluation of pathogenicity and therapeutic effectiveness of antibiotics using silkworm Nocardia infection model.

Nocardia is a ubiquitous environmental microbe that causes nocardiosis against immunosuppressed and immunocompromised hosts. The assay system for the quantitative evaluation of virulence of Nocardia sp. or therapeutic effectiveness of antimicrobials for treatment of nocardiosis is not established so far. In this study, we established an infection model of Nocardia sp. using silkworm as an alternative animal model. We found that all tested Nocardia sp. such as Nocardia asiatica, Nocardia elegans, Nocardia exalbida, Nocardia farcinica, and Nocardia nova killed silkworm and their killing ability were different by species. N. farcinica showed higher pathogenicity among tested strain, similar to the mouse model as previously reported. In addition, we found that antimicrobials such as amikacin and minocycline showed therapeutic effectiveness in silkworms infected with N. farcinica, and we could determine effective doses 50 (ED50) values. These results suggest that silkworm is a useful alternative animal to evaluate the pathogenicity of Nocardia pathogen and the therapeutic effects of antimicrobials against Nocardia sp. in a quantitative manner.

Case Report: Spontaneous Carinal Perforation and Bronchonodal Fistula due to Pulmonary Nocardiosis in an HIV-Infected Patient.

In clinical practice, nocardial infection is a rare opportunistic infection coexisting with potentially life-threatening condition, particularly in patients with HIV infection. Although the incidence remains low, it is still associated with high morbidity and mortality. The lung is a typical site involved in this organism, and complicating conditions can be resulted from local disruption and or destruction of adjacent structures. To our knowledge, this is the first case of pulmonary nocardiosis in an HIV-infected patient who is complicated with spontaneous carinal perforation, leading to develop bronchonodal fistula.

Isolation of nocobactin NAs as Notch signal inhibitors from Nocardia farcinica, a possibility of invasive evolution.

Notch signaling inhibitors with the potential of immune suppressor production by pathogenic bacteria for easy host infection were searched from extracts of Nocardia sp. Nocobactin NA-a (compound 1) and nocobactin NA-b (compound 2), which have been suggested as pathogenesis factors, were isolated from N. farcinica IFM 11523 isolated from the sputum of a Japanese patient with chronic bronchitis. Compounds 1 and 2 showed Notch inhibitory activities with IC50 values of 12.4 and 17.6 µM, respectively. Compound 1 and 2 decreased of Notch1 protein, Notch intracellular domain, and hairy and enhancer of split 1, which is a Notch signaling target protein. In addition, compounds 1 and 2 showed cytotoxicity against mouse macrophage-like cell line RAW264.7 with IC50 values of 18.9 and 21.1 µM, respectively. These results suggested that the Notch inhibitors production by pathogenic bacteria may increase pathogen infectivity.

A rare case of isolated cauda equina Nocardia farcinica infection.

Nocardia is a Gram-positive, partially acid-fast, catalase-positive, and urease-positive bacterium that grows aerobically. We present an extremely rare case of cauda equina syndrome due to isolated intramedullary Nocardia farcinica infection. A 44-year-old male presented with low backache and gradually progressive weakness in bilateral lower limbs followed by paraplegia. He was found to have a well-defined, sharply demarcated ring-enhancing lesion located from T11-T12 to L3 vertebral body. He underwent laminectomy and decompression. The histopathological examination revealed a Gram-positive filamentous organism that looks like Nocardia. The culture report was suggestive of Nocardia farcinica. He was then treated with antibiotics and had a remarkable clinical and radiological improvement.

A clinical case report of brain abscess caused by Nocardia brasiliensis in a non-immunocompromised patient and a relevant literature review.

BACKGROUND: Brain abscess due to the Nocardia genus is rare and usually found in immunocompromised patients. The most common subtype implicated is Nocardia farcinica while brain abscess due to Nocardia brasiliensis is comparatively rare. Diagnosis of brain abscess is based mainly on bacteriological culture from pus collected at the site of infection, and brain imaging. Stereotaxic aspiration or surgical resection combined with adequate duration of treatment with antibiotics to which the bacteria are sensitive represent effective treatment strategies. CASE PRESENTATION: We report a rare case of brain abscess caused by Nocardia brasiliensis in a non-immunocompromised patient. He admitted to our hospital twice with a headache. Stereotaxic aspiration was performed at the patient's first appointment at the hospital, and a craniotomy was used to excise the lesion during subsequent abscess recurrence. CONCLUSION: Early diagnosis, reasonable surgical intervention, and adequate duration of treatment with effective antibiotics are critical for treating brain abscess.

Nocardia colonization in contrast to nocardiosis: a comparison of patients' clinical characteristics.

Information on Nocardia colonization of the lower respiratory tract is scarce. The current study is aimed at comparing clinical characteristics between individuals with Nocardia colonization and those with nocardiosis. All patients with Nocardia isolation between 2007 and 2018 at a tertiary hospital in Israel were included. Nocardia isolation was based on biochemical tests together with phenotypic susceptibility and resistance patterns until 2011 and on matrix-assisted laser desorption/ionization time-of-flight mass spectrometer from 2012. We defined nocardiosis as a clinically evident infection related to the isolation of the bacteria, which required antibiotic therapy. We defined colonization as Nocardia isolation with no clinical evidence of disease. The medical charts of all included individuals were independently reviewed by an infectious disease specialist to ensure adequate classification. Logistic regression models were fitted to compare clinical characteristics between the groups. Fifteen (20%) of the 75 Nocardia isolations met the criteria for colonization. Of those, 13 (87%) had background illnesses. Having a chronic pulmonary disease was associated with increased likelihood of Nocardia colonization, in contrast to nocardiosis (adjusted odds ratio [OR] 4.06, 95% confidence interval [CI] 1.06-15.48, p = 0.040), while an inverse association was found with corticosteroid therapy (adjusted OR 0.21, 95% CI 0.06-0.74, p = 0.015). Nocardia colonization of the lower respiratory tract accounts for a substantial proportion of all Nocardia isolations. Individuals colonized with Nocardia typically have chronic pulmonary disease and are less frequently treated with corticosteroid than patients with nocardiosis.

A novel experimental immunomodulatory therapy against Nocardia brasiliensis in a BALB/c murine model.

BACKGROUND: Mycetoma is recognized as a neglected tropical disease and there are still therapeutic challenges, especially in cases recalcitrant to standard therapy or with high risk of dissemination. Subcultures have been used previously to decrease the virulence of human pathogens. Previous reports have demonstrated that after carrying out 200 subcultures of Nocardia brasiliensis, a decrease in virulence was observed. AIM: To evaluate the effect of attenuated N. brasiliensis strains on the development of lesions in an established mycetoma infection. METHODS: Female 8-12-week-old BALB/c mice were injected with N. brasiliensis suspension to establish a mycetoma. Sixty mice were selected and divided into three groups: two of these groups were inoculated in the dorsum with N. brasiliensis subcultured 200 and 400 times, respectively, while the third group served as control. The thickness of each lesion was measured with calipers every week for 12 weeks. RESULTS: After 12 weeks, we observed that inoculation of 1 × 105 colony-forming units of attenuated N. brasiliensis strains was able to modify the natural history of the infection, with a decrease in the size of the lesions, particularly with P400, compared with the control group (P < 0.01). CONCLUSION: In this experimental evaluation of an immunomodulatory therapy with attenuated N. brasiliensis strains in a murine model, there was a greater stability in the size of the lesion over time in BALB/c mice inoculated with the P400 strain. This treatment could open the possibility of using the attenuated strain as immunomodulatory therapy in patients recalcitrant to standard therapy, with high risk of dissemination or who develop drug-related adverse effects.

Nocardia amikacinitolerans and cytomegalovirus: distinctive clinical and radiological characterization of the rare etiologies of brain abscesses: report of 2 cases.

Central nervous system infections in immunosuppressed patients are rare but potentially lethal complications that require swift diagnoses and intervention. While the differential diagnosis for new lesions on neuroradiological imaging of immunosuppressed patients typically includes infections and neoplasms, image-based heuristics to differentiate the two has been shown to have variable reliability.The authors describe 2 rare CNS infections in immunocompromised patients with atypical physical and radiological presentations. In the first case, a 59-year-old man, who had recently undergone a renal transplantation, was found to have multifocal Nocardia amikacinitolerans abscesses masquerading as neoplasms on diffusion-weighted imaging (DWI); in the second case, a 33-year-old man with suspected recurrent Hodgkin's lymphoma was found to have a nonpyogenic abscess with cytomegalovirus (CMV) encephalitis.As per review of the literature, this appears to be the first case of brain abscess caused by N. amikacinitolerans, a recently isolated superbug. Despite confirmation through brain biopsy later on in case 1, the initial radiological appearance was atypical, showing subtle diffusion restriction on DWI. Similarly, the authors present a case of CMV encephalitis that presented as a ring-enhancing lesion, which is extremely rare. Both cases draw attention to the reliability of neuroimaging in differentiating an abscess from a neoplasm.

[Hemophagocytic lymphohistiocytosis with granulomatosis and diffuse T-cell infiltration associated with disseminated Nocardiosis and pulmonary infection due to Streptomyces spp]. / Syndrome d'activation macrophagique associé à une granulomatose et une infiltration lymphocytaire T CD4 diffuse révélant une nocardiose disséminée et une infection pulmonaire à Streptomyces spp.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome frequently secondary to infectious disease, especially in immuno-compromised patients. We report a HLH secondary to disseminated nocardiosis and Streptomyces spp pulmonary infection. CASE REPORT: A 69-years-old women had recent subcutaneous nodules of the forearms and loins associated with peripheral neuropathy and pulmonary nodule of the right upper lobe. Cutaneous biopsy revealed granuloma. Cutaneous lesions worsened and the patient developed a HLH with probable cardiac and neurological involvement, associated with cutaneous granulomatosis and diffuse polyclonal lymphocyte proliferation. Nocardia PCR was positive in cutaneous biopsy. Pulmonary samples revealed Streptomyces in culture and Nocardia in PCR. The evolution under antibiotic treatment was favorable. CONCLUSION: Recent diagnosis of HLH without obvious etiology should lead to etiological investigation, including the search for infections with slow-growing bacteria such as Nocardia or Streptomyces spp.

Disseminated Nocardia farcinica infection presenting as a paravertebral abscess in a patient with systemic lupus erythematosus.

Disseminated Nocardia infections occur particularly in immunosuppressed hosts and are most often due to Nocardia farcinica, Nocardia nova, and Nocardia cyriacigeorgica. Here, we report an unusual case of disseminated N. farcinica infection presenting as a paravertebral abscess in a patient with systemic lupus erythematosus.

Immunocompetent patient with a brain abscess caused by Nocardia beijingensis in Latin America: A case report.

RATIONALE: Nocardia species are not commonly referred as primary infectious entities but rather as opportunistic pathogens. Infectious cases of Nocardia spp. in immunocompetent individuals are rare. PATIENT CONCERNS: An immunocompetent 58-year-old patient presented with recurrent headaches. DIAGNOSIS: A brain abscess was found and surgically drained. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and heat shock protein 65/16S-23S rRNA gene intergenic spacer genotyping from the sample revealed the etiological agent as Nocardia beijingensis. INTERVENTIONS: Meropenem/amikacin/Trimethoprim-sulfamethoxazole were administered. OUTCOMES: The infection persisted leading to the patient's death. LESSONS: Here we present the first case of N. beijingensis infection of the central nervous system in an immunocompetent patient from Latin America. Further inquiry is needed to establish whether this species is more virulent than other Nocardia isolates.

Isolation and characterization of bacteriophage NTR1 infectious for Nocardia transvalensis and other Nocardia species.

We describe here the isolation and characterization of the bacteriophage, NTR1 from activated sludge. This phage is lytic for Nocardia transvalensis, Nocardia brasiliensis and Nocardia farcinica. NTR1 phage has a genome sequence of 65,275 bp in length, and its closest match is to the Skermania piniformis phage SPI1 sharing over 36% of its genome. The phage belongs to the Siphoviridae family, possessing a long non-contractile tail and icosahedral head. Annotation of the genome reveals 97 putative open reading frames arranged in the characteristic modular organization of Siphoviridae phages and contains a single tRNA-Met gene.

High Intraspecific Genetic Diversity of Nocardia brasiliensis, a Pathogen Responsible for Cutaneous Nocardiosis Found in France: Phylogenetic Relationships by Using sod and hsp65 Genes.

This study aims at genetic characterization and phylogenetic relationships of Nocardia brasiliensis focusing by using housekeeping rrs, hsp65, and sodA genes. N. brasiliensis is the species responsible for 80% of cases of actinomycetoma, one form of cutaneous nocardiosis which occurs mainly in tropical regions reaching immunocompetent patients in which the disease can lead to amputation. We analyze 36 indigenous cases of N. brasiliensis that happened in France. Phylogenetic analysis targeting rrs gene showed no robustness at phylogenetic nodes level. However, the use of a concatenation of hsp65 and sodA genes showed that the tested strains surprisingly ranked in 3 well-defined genotypes. Genotypes 2 and 3 were phylogenetically closer to each other and both diverged from genotype 1 sustained by a high bootstrap of 81%. This last genotype hosts all the cases of pulmonary forms (3), the sole cerebral form, and almost all the cases of immunocompromised patients (3 out of 4). Moreover, excepting one of them, all the strains belonging to this group present a susceptibility to imipenem which is not the case in the other genotypes that rarely count among them strains being susceptible to this drug. The haplotype diversity (Hd) of hsp65 (0.927) and sodA (0.885) genes was higher than that of rrs (0.824). For this gene, we obtained 16 polymorphic sites whereas, for hsp65 and sodA genes, up to 27 and 29 were identified, respectively. This study reveals that these two genes have an important genetic discriminatory power for the evaluation of the intraspecies genetic variability of N. brasiliensis and they may be useful for identification purposes at species level. This study also reveals the possible existence of a new species harbored by genotype 1.

Absceso cerebral por Nocardia spp. en pacientes inmunocompetentes: presentación de 2 casos / Cerebral abscess by Nocardia spp. in immunocompetent patients: report of 2 cases

Nocardia corresponde a un género de bacterias gram positivo que puede producir compromiso pulmonar, sistémico y abscesos cerebrales, especialmente en pacientes inmunocomprometidos. La infección cerebral por Nocardia spp es extremadamente infrecuente en pacientes inmunocompetentes, por lo cual se reportan dos casos: caso 1: mujer de 61 años, sana, consulta por cefalea y paresia en hemicuerpo izquierdo. Estudio con TAC y RM de encéfalo demuestran absceso cerebral. Se inició tratamiento con ceftriaxona mas cloxacilina y fue drenado quirúrgicamente. En el cultivo del LCR se aisló Nocardia spp. cambiándose esquema a cotrimoxazol con meropenem por 6 semanas. Caso 2: varón de 72 años, hipertenso y tabáquico crónico. Consultó por cefalea, paresia de extremidad inferior derecha y pérdida de visión de ojo derecho. Estudio con TAC y RM de encéfalo objetiva absceso cerebral parietal izquierdo. Se inició tratamiento con ceftriaxona, metronidazol y vancomicina. Se realizó drenaje quirúrgico. El cultivo de absceso resultó positivo para Nocardia spp, ajustándose esquema a cotrimoxazol y meropenem por 6 semanas. Requirió tratamiento prolongado por presentar lenta regresión clínica e imagenoló- gica.

Nocardia is a gram positive bacterial genus. Is involved in pulmonary, systemic and brain abscess usually in immunocompromised patients. Nocardia spp. brain infection is extremely rare in immunocompetent patients, hereby we report 2 cases: case 1: 61 years old woman, without morbid conditions, consulted for headache and left hemiparesis. Study with CT and MRI of encephalon shows brain abscess. Treatment with ceftriaxone plus cloxacilin and surgical drainage were started. In CSF culture, Nocardia spp. was obtained. Scheme was changed to cotrimoxazole with meropenem to complete 6 weeks. Case 2: male of 72 years old, history of smoking and hypertension. Consulted for headache, paresis of right leg and loss of vision of the right eye. CT and MRI showed left parietal brain abscess. Treatment with ceftriaxone, metronidazole and vancomycin were started. Surgical drainage was performed. Abscess culture was positive for Nocardia spp., adjusting scheme to cotrimoxazole and meropenem for 6 weeks. It required prolonged treatment due to slow imaging and clinical regression.