IFN-γ enhances protective efficacy against Nocardia seriolae infection in largemouth bass (Micropterus salmoides).

Introduction: Nocardia seriolae adversely impacts a diverse range of fish species, exhibiting significant pathogenic characteristics that substantially impede the progress of aquaculture. N. seriolae infects in fish has a long incubation period, and clinical symptoms are not obvious in the early stages. There is presently no viable and eco-friendly approach to combat the spread of the disease. According to reports, N. seriolae primarily targets macrophages in tissues after infecting fish and can proliferate massively, leading to the death of fish. Interferon-gamma (IFN-γ) is a crucial molecule that regulates macrophage activation, but little is known about its role in the N. seriolae prevention. Methods: IFN-γ was first defined as largemouth bass (Micropterus salmoides, MsIFN-γ), which has a highly conserved IFN-γ characteristic sequence through homology analysis. The recombinant proteins (rMsIFN-γ) were obtained in Escherichia coli (E. coli) strain BL21 (DE3). The inflammatory response-inducing ability of rMsIFN-γ was assessed in vitro using monocytes/macrophages. Meanwhile, the protective effect of MsIFN-γ in vivo was evaluated by N. seriolae infection largemouth bass model. Results: In the inflammatory response of the monocytes/macrophages activated by rMsIFN-γ, various cytokines were significantly increased. Interestingly, interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-a) increased by 183- and 12-fold, respectively, after rMsIFN-γ stimulation. rMsIFN-γ improved survival by 42.1% compared with the control. The bacterial load in the liver, spleen and head kidney significantly decreased. rMsIFN-γ was also shown to better induce increased expression of IL-1ß, TNF-α, hepcidin-1(Hep-1), major histocompatibility complex I (MHCI), and MHC II in head kidney, spleen and liver. The histopathological examination demonstrated the transformation of granuloma status from an early necrotic foci to fibrosis in the infection period. Unexpectedly, the development of granulomas was successfully slowed in the rMsIFN-γ group. Discussion: This work paves the way for further research into IFN-γ of largemouth bass and identifies a potential therapeutic target for the prevention of N. seriolae.

Clinical characteristics and drug resistance of Nocardia in Henan, China, 2017-2023.

BACKGROUND: The aim of this study was to investigate the clinical features of Nocardia infections, antibiotic resistance profile, choice of antibiotics and treatment outcome, among others. In addition, the study compared the clinical and microbiological characteristics of nocardiosis in bronchiectasis patients and non-bronchiectasis patients. METHODS: Detailed clinical data were collected from the medical records of 71 non-duplicate nocardiosis patients from 2017 to 2023 at a tertiary hospital in Zhengzhou, China. Nocardia isolates were identified to the species level using MALDI-TOF MS and 16S rRNA PCR sequencing. Clinical data were collected from medical records, and drug susceptibility was determined using the broth microdilution method. RESULTS: Of the 71 cases of nocardiosis, 70 (98.6%) were diagnosed as pulmonary infections with common underlying diseases including bronchiectasis, tuberculosis, diabetes mellitus and chronic obstructive pulmonary disease (COPD). Thirteen different strains were found in 71 isolates, the most common of which were N. farcinica (26.8%) and N. cyriacigeorgica (18.3%). All Nocardia strains were 100% susceptible to both TMP-SMX and linezolid, and different Nocardia species showed different patterns of drug susceptibility in vitro. Pulmonary nocardiosis is prone to comorbidities such as bronchiectasis, diabetes mellitus, COPD, etc., and Nocardia is also frequently accompanied by co-infection of the body with pathogens such as Mycobacterium and Aspergillus spp. Sixty-one patients underwent a detailed treatment regimen, of whom 32 (52.5%) received single or multi-drug therapy based on TMP-SMX. Bronchiectasis was associated with a higher frequency of Nocardia infections, and there were significant differences between the bronchiectasis and non-bronchiectasis groups in terms of age distribution, clinical characteristics, identification of Nocardia species, and antibiotic susceptibility (P < 0.05). CONCLUSIONS: Our study contributes to the understanding of the species diversity of Nocardia isolates in Henan, China, and the clinical characteristics of patients with pulmonary nocardiosis infections. Clinical and microbiologic differences between patients with and without bronchiectasis. These findings will contribute to the early diagnosis and treatment of patients.

Disseminated Nocardia nova in a child with relapsed acute lymphoblastic leukemia: a case report.

BACKGROUND: Nocardiosis is a rare infection that typically results from inhalation of or inoculation with Nocardia organisms. It may cause invasive disease in immunocompromised patients. This case describes nocardiosis with bacteremia and pulmonary involvement in a child with a hematologic malignancy. CASE PRESENTATION: A boy with testicular relapsed acute lymphoblastic leukemia with marrow involvement presented with sudden onset of fever, body aches, headaches, chills, and moderate respiratory distress during continuation 2 chemotherapy. Radiographic imaging demonstrated consolidation and ground glass opacities in bilateral lower lungs. Central line blood cultures grew Nocardia nova complex, prompting removal of the central line and initiation of triple therapy with imipenem-cilastatin, linezolid, and trimethoprim-sulfamethoxazole with rapid improvement of symptoms. Antibiotic susceptibilities showed a multidrug-susceptible isolate. The patient is anticipated to remain on trimethoprim-sulfamethoxazole for at least 12 months. CONCLUSIONS: In an immunocompromised child, blood cultures, chest imaging, and head imaging can aid in the diagnosis of disseminated nocardiosis. Long-term antibiotic therapy is necessary, guided by the organism and simplified with the results of antimicrobial susceptibility testing.

Identifying the in vivo-induced antigenic genes is a strategy to develop DNA vaccine against Nocardia seriolae in hybrid snakehead (Channa maculata ♀ × Channa argus ♂).

Nocardia seriolae has been identified as the causative agent of fish nocardiosis, resulting in serious economic losses in aquaculture. With an aim to screen potential candidates for vaccine development against N. seriolae, the in vivo-induced genes of N. seriolae in hybrid snakehead (Channa maculate ♀ × Channa argus ♂) model were profiled via in vivo-induced antigen technology (IVIAT) in the present study, and 6 in vivo-induced genes were identified as follows: IS701 family transposase (is701), membrane protein insertase YidC (yidC), ergothioneine biosynthesis glutamate-cysteine ligase (egtA), molybdopterin respectively-dependent oxidoreductase (mol), phosphoketolase family protein (Ppl), hypothetical protein 6747 (hp6747). Additionally, the yidC was inserted into eukaryotic expression vector pcDNA3.1-myc-his-A to construct a DNA vaccine named as pcDNA-YidC to evaluate immunoprotection in hybrid snakehead after artificial challenge with N. serioale. Results showed that the transcription of yidC was detected in spleen, trunk kidney, muscle and liver in vaccinated fish, suggesting that this antigenic gene can be recombinantly expressed in fish. Meanwhile, indexes of humoral immunity were evaluated in the vaccinated fish through assessing specific-antibody IgM and serum enzyme activities, including lysozyme (LZM), superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Quantitative real-time PCR analysis indicated that pcDNA-YidC DNA vaccine could notably enhance the expression of immune-related genes (CD4、CD8α、MHCIIα、TNFα、IL-1ß and MHCIα) in 4 tissues (spleen, trunk kidney, muscle and liver) of the vaccinated fish. Finally, an immuno-protection with a relative survival rate of 65.71 % was displayed in vaccinated fish in comparison to the control groups. Taken together, these results indicate that pcDNA-YidC DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, indicating that IVIAT is a helpful strategy to screen the highly immunogenic antigens for vaccine development against fish nocardiosis.

Severe disseminated Nocardia brasiliensis pneumonia with normal immune function: A case report.

RATIONALE: Members of the genus Nocardia brasiliensis are Gram-positive, aerobic bacteria and exist ubiquitously in most environments. In recent years, the incidence of Nocardia brasiliensis has increased significantly and become a global concern. It may be predominantly caused pulmonary infections in immunocompromised hosts. Interestingly, however, we found that it can be present not only on immunocompromised hosts, but also to infect patients with a normal immune system. PATIENT CONCERNS: We report a very rare case of a 49-year-old immunocompetent man with disseminated Nocardia brasensis pneumonia. He had a fever for 14 days (maximum temperature about 38°C) and a history of mass rupture. DIAGNOSES: Severe Disseminated Nocardia brasiliensis pneumonia with normal immune function. INTERVENTIONS: No. OUTCOMES: The patient was finally diagnosed with Severe Disseminated Nocardia brasiliensis pneumonia and received compound sulfamethoxazole treatment for 4 months. LESSONS SUBSECTIONS: Our report highlights when cold pus appears in soft tissues such as the lower limbs, neck, nose, scalp, etc, should prompt timely evaluation and biopsy for definitive diagnosis. Be alert to a normally immunocompetent, disseminated Nocardia brasiliensis infection. Early recognition and effective treatment are necessary conditions for successful results. This would allow for better disease prognostication while enabling physicians to develop more effective treatment strategies.

Gastrointestinal dysbiosis induced by Nocardia sp. infection in tilapia.

Nocardiosis has caused high mortalities among fish cultures; however, the effects of Nocardia infections in the fish gastrointestinal microbiota are unknown. In this research, tilapia was infected with Nocardia sp., to analyze the effect of infection on the gastrointestinal microbiota. Tilapia infected with Nocardia sp. reported a 46 % survival (100 % in non-infected). Moreover, the infection caused severe damage to the stomach microbiota, with a loss of diversity and a significant increase of Proteobacteria (94.8 %), resulting in a negative correlation network between Proteobacteria and other important phyla. Nocardia sp. is an emerging pathogen capable of inducing dysbiosis and causing significant mortalities.

Bioprospecting the potential of metabolites from a Saharan saline soil strain Nocardiopsis dassonvillei GSBS4.

Saharan soil samples collected in El-Oued province have been investigated for actinobacteria as a valuable source for the production of bioactive metabolites. A total of 273 isolates were obtained and subjected to antagonistic activity tests against human pathogenic germs. A strain with a broad-spectrum antimicrobial activity was selected and identified as Nocardiopsis dassonvillei GSBS4, with high sequence similarities to N. dassonvillei subsp. dassonvilleiT X97886.1 (99%) based on polyphasic taxonomy approach and 16S ribosomal ribonucleic acid gene sequence analysis. The GSBS4 ethyl acetate crude extract showed strong antibacterial activity towards pathogenic bacteria and Candida albicans. It inhibited biofilm formation by Staphylococcus aureus and methicillin-resistant S. aureus with minimum inhibitory concentrations estimated at 0.144 and 1.15 mg·mL-1 , respectively. A 44% biofilm reduction was obtained for S. aureus and 61% for Pseudomonas aeruginosa. Furthermore, phenols composition of the crude extract showed a significant dose-dependent antioxidant activity by α-diphenyl-ß-picrylhydrazyl (57.21%) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (64.29%) radicals scavenging assays. Although no inhibition was obtained on human coronavirus human coronavirus (HCoV) 229E and on model enterovirus (poliovirus 1) infection, a dose-dependent increase in cell viability of HCoV 229E-infected cells was noticed as the viability increased from 21% to 37%. Bioassay-guided fractionation of the crude extract gave a fraction showing antibacterial activity, which was analyzed by liquid chromatography-electrospray mass spectrometric technique, providing structural features on a major purple metabolite.

Fifteen years of phenotypic and genotypic surveillance and antibiotic susceptibility pattern of Actinomycetes (Mycobacterium, Nocardia, Rhodococcus, etc.) in clinical and environmental samples of Iran.

Actinomycetes, ubiquitous in the natural world, have been known to inflict infections upon both immunocompromised and healthy individuals. Interestingly enough, these species are oftentimes found residing within the microbiota of humans and animals alike. Unfortunately, these infections are frequently misdiagnosed as more sinister ailments such as malignancy or tuberculosis. Due to this issue, this review deals with 15 years of study on clinical and environmental samples to determine Actinomycetes' prevalence, isolation, identification, and antibiotic susceptibility pattern in Iran by Davood Azadi et al. According to the Davood Azadi framework, we searched the following databases: PubMed/MEDLINE, Embase, Scopus, Web of Science, SID, and Google Scholar in the period from 2007 to 2023. This review aimed to provide an overview of the most recent techniques for collecting environmental samples, cultivating them, and identifying the Actinomycetes group's members. The isolation of Actinomycetes from clinical and ecological sources is becoming more prevalent and should be a concern for health authorities in developing countries. Health centers should take action to increase awareness of diagnostic criteria and management guidelines for actinomycete diseases. Improvements in national and regional reference laboratories may also aid in accurately diagnosing these diseases.

[A case of disseminated nocardiosis in a non-immunosuppressed host].

Nocardia is an opportunistic pathogen that most commonly affects immunosuppressed hosts, while disseminated infections in healthy hosts are rare. In this paper, we described a case of disseminated Nocardia infection in a non-immunosuppressed host whose initial imaging was strikingly similar to systemic metastasis from a tumor. Since no tumor cells were found in any of the numerous biopsies taken, we considered infection by specific pathogens before metagenomic next-generation sequencing of a lumbar spine tissue biopsy finally confirmed the diagnosis of Nocardia infection. To help doctors better understand this condition and avoid misdiagnosis a, this article provided a summary of the clinical characteristics, diagnostic techniques, and therapeutic options for disseminated nocardiosis.

Rare occurrence of pulmonary coinfection involving Aspergillus fumigatus and Nocardia cyriacigeorgica in immunocompetent patients based on NGS: A case report and literature review.

RATIONALE: In our search on PubMed, we found that reports of co-infections involving Aspergillus fumigatus and Nocardia cyriacigeorgica in the literature are notably scarce. Most cases have been documented in patients with compromised immune systems or underlying pulmonary conditions. In contrast, our patient did not present with any of these risk factors. Furthermore, there have been no recent incidents such as near-drowning or other accidents in the patient history. To the best of our knowledge, this case represents a hitherto unreported clinical scenario. To enhance comprehension, we conducted a comprehensive literature review by compiling a total of 20 case reports (spanning from 1984 to 2023) on co-infections involving Aspergillus and Nocardia species, retrieved from PubMed. PATIENT CONCERNS AND DIAGNOSIS: Chest CT revealed the presence of multiple nodules and clustered high-density shadows in both lungs. Bronchoscopy revealed mucosal congestion and edema in the apical segment of the right upper lobe of the lung, along with the presence of 2 spherical polypoid new organisms. The pathological analysis reported severe chronic inflammation with evidence of Aspergillus within the tissue. Next-Generation Sequencing of bronchoalveolar lavage fluid revealed the presence of reads corresponding to A fumigatus and N cyriacigeorgica. Positive cultures for A fumigatus and the Nocardia genus were yielded by prolonging the incubation of samples in the microbiology laboratory. INTERVENTIONS: Treatment with voriconazole for A fumigatus and sulfamethoxazole-trimethoprim for N cyriacigeorgica infection was given. OUTCOMES: The patient improved and was discharged. After 6 months of telephone follow-up, the patient reported no clinical symptoms, discontinued the medication on his own. LESSONS: A fumigatus and N cyriacigeorgica can manifest as a co-infection in immunocompetent patients. Clinicians should prioritize the significant advantages and value of NGS in detecting rare and mixed pathogens associated with pulmonary infections.

Pulmonary nocardiosis following nodular bronchiectatic Mycobacterium avium complex pulmonary disease in an immunocompetent patient.

A woman in her 70s with a history of nodular bronchiectatic Mycobacterium avium complex pulmonary disease (MAC-PD) presented with an exacerbated productive cough and worsening findings on chest imaging. Although repeated sputum culture tests were negative for acid-fast bacilli and only revealed normal respiratory flora, a bronchoscopy identified Nocardia sp. Consequently, she was diagnosed with pulmonary nocardiosis and was successfully treated with levofloxacin. It is known that pulmonary nocardiosis can manifest in immunocompetent individuals with bronchiectasis. For cases of refractory nodular bronchiectatic MAC-PD, it is vital to consider bronchoscopy to identify potential co-infections, such as Nocardia.

Lung cancer patient with Tropheryma whipplei and Nocardia co-infection.

A 34-year-old male presented with lung shadow and was asymptomatic during medical examination. The patient had a prior history of thyroid tumors. Imaging manifestation showed a nodule in the medial segment of the right middle lobe, with partial obstruction of the distal bronchus within the lesion. Ground-glass and inflammatory nodules were observed in the anterior segment of the right upper lobe, as well as chronic inflammatory changes in the lower lobe of the right lung. Lung histopathological examination suggested invasive adenocarcinoma. A morphological examination of the bronchoalveolar lavage fluid revealed the presence of Tropheryma whipplei (TW) and Nocardia. Although TW infection has been reported in cancer patients, co-infection with Nocardia is a unique occurrence in this case. Opportunistic pathogens are common in immunocompromised patients but in this case, the patient was a young adult with normal immunity and an early-stage tumor with TW and Nocardia co-infection. We demonstrated the presence of rare microorganisms through imaging findings, combined with different staining methods of bronchoalveolar lavage fluid and lung tissue sections and evaluation of morphological characteristics. The aim of the present study was to provide early diagnosis and treatment of patients by improving microbial morphological detection.

Subretinal abscess due to nocardia in an immunosuppressed patient: a case report.

Systemic nocardiosis is a rarely occurring pathology, but its hematogenous spread across the eye is even less likely to occur, with only a few recorded cases. Therefore, it is not usually taken into account when a subretinal abscess is being considered for a diagnosis. However, when confronting a case with a history of immunosupression and pulmonary disease, the examination of the ocular fundus may be a very successful approach. With such aim we introduce the case of a 45-year-old immunosupressed male, without a history of pulmonary disease, whose subretinal mass evolution is accordant with an abscess. In the end, being etiologically diagnosed by means of a vitrectomy, it was concluded that the abscess was due to an infection of nocardia cyriacigeorgica, an emergent pathogen. Thus the aforementioned case is to be considered in the present study, along others, in order to shed more light on a disease which may not be readily diagnosed on account of its infrequency.

Skin lesions by Scedosporium apiospermum and Nocardia pulmonary infection in an oncologic patient: a case report.

BACKGROUND: Fungal infections, other than candidiasis and aspergillosis, are an uncommon entity. Despite this, emerging pathogens are a growing threat. In the following case report, we present the case of an immunocompromised patient suffering from two serious opportunistic infections in the same episode: the first of these, Nocardia multilobar pneumonia; and the second, skin infection by Scedosporium apiospermum. These required prolonged antibacterial and antifungal treatment. CASE PRESENTATION: This case is a 71-year-old oncological patient admitted for recurrent pneumonias that was diagnosed for Nocardia pulmonary infection. Nervous system involvement was discarded and cotrimoxazole was started. Haemorrhagic skin ulcers in the lower limbs appeared after two weeks of hospital admission. We collected samples which were positive for Scedosporium apiospermum and we added voriconazole to the treatment. As a local complication, the patient presented a deep bruise that needed debridement. We completed 4 weeks of intravenous treatment with slow improvement and continued with oral treatment until the disappearance of the lesions occurs. CONCLUSIONS: Opportunistic infections are a rising entity as the number of immunocompromised patients is growing due to more use of immunosuppressive therapies and transplants. Clinicians must have a high suspicion to diagnose and treat them. A fluid collaboration with Microbiology is necessary as antimicrobial resistance is frequent.

Discovery and Biosynthesis of the Cytotoxic Polyene Terpenomycin in Human Pathogenic Nocardia.

Nocardia are opportunistic human pathogens that can cause a range of debilitating and difficult to treat infections of the lungs, brain, skin, and soft tissues. Despite their close relationship to the well-known secondary metabolite-producing genus, Streptomyces, comparatively few natural products are known from the Nocardia, and even less is known about their involvement in the pathogenesis. Here, we combine chemistry, genomics, and molecular microbiology to reveal the production of terpenomycin, a new cytotoxic and antifungal polyene from a human pathogenic Nocardia terpenica isolate. We unveil the polyketide synthase (PKS) responsible for terpenomycin biosynthesis and show that it combines several unusual features, including "split", skipped, and iteratively used modules, and the use of the unusual extender unit methoxymalonate as a starter unit. To link genes to molecules, we constructed a transposon mutant library in N. terpenica, identifying a terpenomycin-null mutant with an inactivated terpenomycin PKS. Our findings show that the neglected actinomycetes have an unappreciated capacity for the production of bioactive molecules with unique biosynthetic pathways waiting to be uncovered and highlights these organisms as producers of diverse natural products.

Periocular Infection With Nocardia nova Following Dacryocystorhinostomy With Silicone Stent Intubation.

Nocardia species are aerobic, rod-shaped, Gram-positive bacteria that are ubiquitous throughout the environment. Nocardia nova has been reported as the second most prevalent Nocardia species. However, reports of ocular and periocular infection caused by this organism are rare. The authors present a case of a 58-year-old woman with a medical history of acquired nasolacrimal duct obstruction of the left eye who underwent a revision dacryocystorhinostomy with silicone stent intubation and developed a surgical site infection that was culture-positive for N. nova . Treatment consisted of removal of the silicone stent and a prolonged course of oral antibiotics, resulting in the patient's full recovery. This is the second reported case of postoperative periocular N. nova infection after dacryocystorhinostomy and silicone stent intubation.

Occipital Nocardia Abscess Presenting With Positive Visual Phenomenon and Quadrantanopsia.

ABSTRACT: A 74-year-old man with chronic obstructive pulmonary disease, glaucoma, and Stage IIIB squamous cell lung cancer experienced several minutes of flashing lights in his right visual hemifield, followed by onset of a right visual field defect. On examination, the patient had a right homonymous hemianopsia that was most dense inferiorly by confrontation testing. Emergent CT scan of the head revealed a 2.5 × 3 cm hypodensity in the left occipital lobe, which was interpreted as an acute stroke. Continuous EEG monitoring captured left posterior quadrant seizures that were temporally correlated to the positive visual phenomena. Subsequent MRI of the brain with and without contrast revealed a conglomerate of centrally necrotic and peripherally enhancing mass lesions. On biopsy, a thick purulent material was drained and Gram stain of the sample revealed gram-positive beaded rods, which speciated to Nocardia farcinica . The patient was treated with a six-week course of intravenous meropenem and a one-year course of oral trimethroprim-sulfamethoxazole. On follow-up, the patient experienced resolution of the right visual field deficit.

Nocardia sputorum sp. nov., an actinobacterium isolated from clinical specimens in Japan.

Two novel actinobacteria, designated IFM 12276T and IFM 12275, were isolated from clinical specimens in Japan, and their taxonomic positions were investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strains IFM 12276 T and IFM 12275 have completely identical 16S rRNA gene sequences and were closely related to members of the genus Nocardia. The highest 16S rRNA gene sequence similarity was observed to Nocardia beijingensis (99.6 %) and Nocarida sputi (99.6 %), followed by Nocardia niwae (99.3 %) and Nocardia araoensis (99.3 %). The whole-cell hydrolysates of strains IFM 12276T and IFM 12275 contained meso-diaminopimelic acid, arabinose and galactose. The acyl type of muramic acid was N-glycolyl. The predominant isoprenoid quinone was MK-8(H4, ω-cycl.) and the principal polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides. Strains IFM 12276T and IFM 12275 contained mycolic acids that co-migrated with those from the type strain of N. niwae. These chemotaxonomic features corresponded to those of the genus Nocardia. Meanwhile, the differences in some phenotypic characteristics, along with the results of average nucleotide identity and digital DNA-DNA hybridization analyses, indicated that strains IFM 12276 T and IFM 12275 should be distinguished from the recognized species of the genus Nocardia. Therefore, these strains represent a novel species of the genus Nocardia, for which the name Nocardia sputorum sp. nov. is proposed. The type strain is IFM 12276T (=NBRC 115477T=TBRC 17096T).