Mycobacterium Marinum Infection Research Articles

Mycobacterium marinum infection in a patient with Crohn's disease on anti-tumor necrosis factor treatment.

Mycobacterium marinum infection in a patient with Crohn's disease on anti-tumor necrosis factor treatment.

Syringaldehyde Exhibits Antibacterial and Antioxidant Activities against Mycobacterium marinum Infection.

Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis (Mtb), which has a unique resistance to many antimicrobial agents. TB has emerged as a significant worldwide health issue because of the rise of multidrug-resistant strains causing drug-resistant TB (DR-TB). As a result, the development of new drugs or effective strategies is crucial for patients with TB. Mycobacterium marinum (Mm) and Mtb are both species of mycobacteria. In zebrafish, Mm proliferates and forms chronic granulomatous infections, which are similar to Mtb infections in lung tissue. Syringaldehyde (SA) is a member of the phenolic aldehyde family found in various plants. Here, we investigated its antioxidative and antibacterial properties in Mm-infected cells and zebrafish. Our results demonstrated that SA inhibits Mm-infected pulmonary epithelial cells and inhibits the proliferation of Mm in Mm-infected zebrafish, suggesting that SA provides an antibacterial effect during Mm infection. Further study demonstrated that supplementation with SA inhibits the production of malondialdehyde (MDA) and reactive oxygen species (ROS) and increases the levels of reduced glutathione (GSH) in Mm-infection-induced macrophages. SA inhibits the levels of MDA in Mm-infected zebrafish, suggesting that SA exerts antioxidative effects in vivo. Additionally, we found that SA promotes the expression of NRF2/HO-1/NQO-1 and the activation of the AMPK-α1/AKT/GSK-3β signaling pathway. In summary, our data demonstrated that SA exerts antioxidative and antibacterial effects during Mm infection both in vivo and in vitro and that the antioxidative effects of SA may be due to the regulation of NRF2/HO-1/NQO-1 and the AMPK-α1/AKT/GSK-3β signaling pathway.

ATYPICAL MYCOBACTERIAL INFECTION

We describe a 47-year-old healthy man who, after an injury to the third finger of the right hand, developed a reddened papule that did not disappear. Over a period of three months, edema developed on the finger and dorsum of the right hand, followed by several variegated nodules along the 3rd finger, dorsum of the right hand, and right forearm. There are no subjective complaints. The patient has an aquarium at home, and the complaints coincide with a period of growth of the fish in it. The diagnosis of Mycobacterium marinum infection is made on the basis of history, clinical picture, histology and molecular genetic testing for mycobacteria. Treatment with numerous antibacterial agents was carried out, and the long-term (9 months) therapy with clarithromycin, rifampicin and ethambutol, appointed after the diagnostic clarification, led to the cure of the infection. A brief review of the literature on the issue is made.

The tunicamycin derivative TunR2 exhibits potent antibiotic properties with low toxicity in an in vivo Mycobacterium marinum-zebrafish TB infection model.

Tunicamycins (TUN) are well-defined, Streptomyces-derived natural products that inhibit protein N-glycosylation in eukaryotes, and by a conserved mechanism also block bacterial cell wall biosynthesis. TUN inhibits the polyprenylphosphate-N-acetyl-hexosamine-1-phospho-transferases (PNPT), an essential family of enzymes found in both bacteria and eukaryotes. We have previously published the development of chemically modified TUN, called TunR1 and TunR2, that have considerably reduced activity on eukaryotes but that retain the potent antibacterial properties. A mechanism for this reduced toxicity has also been reported. TunR1 and TunR2 have been tested against mammalian cell lines in culture and against live insect cells but, until now, no in vivo evaluation has been undertaken for vertebrates. In the current work, TUN, TunR1, and TunR2 are investigated for their relative toxicity and antimycobacterial activity in zebrafish using a well-established Mycobacterium marinum (M. marinum) infection system, a model for studying human Mycobacterium tuberculosis infections. We also report the relative ability to activate the unfolded protein response (UPR), the known mechanism for the eukaryotic toxicity observed with TUN treatment. Importantly, TunR1 and TunR2 retained their antimicrobial properties, as evidenced by a reduction in M. marinum bacterial burden, compared to DMSO-treated zebrafish. In summary, findings from this study highlight the characteristics of recently developed TUN derivatives, mainly TunR2, and its potential for use as a novel anti-bacterial agent for veterinary and potential medical purposes.

Heat-inactivated mycobacteria activate the toll-like receptor 2 and 4 pathways in the zebrafish model of tuberculosis

Based on previous evidence demonstrating the efficacy of inactivated mycobacteria for the control of fish mycobacteriosis, we explored the protective efficacy of two inactivated Mycobacterium bovis administered via parenteral and mucosal routes against Mycobacterium marinum infection mimicking natural conditions in the zebrafish model of tuberculosis. Although we did not observe a clear effect of any of the immunostimulants on mycobacterial burden, the results showed a significant increase in TLR2 and TLR4 gene expression levels in fishes parenterally immunized with inactivated Bacillus Calmette-Guérin (BCG). Our findings demonstrated that the TLR2 and the TLR4 signaling pathways are involved in the immune response elicited by inactivated mycobacteria in the zebrafish model of tuberculosis and support the use of inactivated mycobacteria in vaccine formulations for the control of mycobacteriosis.

ALA-PDT shortens the course of antibiotic therapy for skin infection caused by Mycobacterium marinum

BackgroundRecently, the number of cases of Mycobacterium marinum infection has increased. Due to the nonspecific clinical manifestations and lack of standardized treatment guidelines, these infections are often misdiagnosed and are challenging to treat. MethodsIn this study, four patients had M. marinum skin infections accompanied by a high-risk exposure history and were diagnosed by bacterial culture and gene chip. Two patients were treated with antibiotic therapy alone, and the other two patients were treated with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics. ResultsAll four patients enrolled in the study were cured with 100 % efficacy. Two patients were cured after receiving two active antibiotics for 4 months. The other two patients, having considered the drug resistance and intolerance described above, were cured after receiving two active antibiotics for 1–1.5 months along with combination therapy with ALA-PDT. ConclusionCombination therapy with ALA-PDT and antibiotics was chosen to shorten the duration of antibiotic treatment and reduce the occurrence of adverse reactions.

P11 A case of Mycobacterium marinum infection in a patient with rheumatoid arthritis recently initiated on adalimumab

P11 A case of <i>Mycobacterium marinum</i> infection in a patient with rheumatoid arthritis recently initiated on adalimumab

Rapid Diagnosis of Mycobacterium marinum Infection on Both Hands using a Combination of Skin Trephination and Metagenomic Next-generation Sequencing.

Abstract is missing (Short communication)

Granuloma features of Mycobacterium marinum infections: A series of 70 retrospective cases.

Granuloma features of Mycobacterium marinum infections: A series of 70 retrospective cases.

A Series of 35 Cutaneous Infections Caused by Mycobacterium marinum in Han Chinese Population

Cutaneous Mycobacterium marinum infection is an increasingly infectious disease presenting unique diagnostic and therapeutic challenges. The aim of this study was to evaluate the differences in time to treatment among patients with different types of skin lesions and who were treated with single or multidrug therapies. In addition, the clinical characteristics of M. marinum infection were explored and the mechanism of the host immune responses was investigated. The electronic medical records of 35 patients with M. marinum infection were reviewed. The clinical characteristics, histopathological and laboratory data, and treatment outcomes were analyzed. Immunohistochemical analysis was performed to clarify the immune mechanisms induced by M. marinum infection in 9 patients and 5 healthy controls. Of the 35 patients, 25 (71.4%) had lesions with sporotrichoid patterns. The duration of patients with sporotrichoid lesions or treatment with multiple drugs was longer, although differences were not significant, possibly due to the small cohort. However, this trend was also observed in previous studies, making it worthy of further attention. Expression levels of cytokines (IFN-γ, IL-4, IL-9, and FOXP3) were significantly upregulated in the patient specimens, whereas there were no significant differences in IL-17 and IL-22 expression levels between the patient and control groups.

Mycobacterium marinum: A Case-Based Narrative Review of Diagnosis and Management.

Skin and soft tissue infections caused by non-tuberculous mycobacteria are occurring more frequently in recent years. However, chronic skin and soft tissue lesions present a challenge for clinicians, as the diagnostic work-up and definitive diagnosis require knowledge and available laboratory resources. We present here the case of a 66-year-old male patient who presented with painful abscess-like nodules on his right hand and forearm, which worsened after treatment with an anti-TNF-a agent. The fluid specimen taken from the lesion was positive for mycobacteria according to the acid-fast stain. Mycobacterium marinum was identified, first by next-generation sequencing and finally grown on culture, after eight weeks. Acknowledging the complexity of diagnosing and managing infections by non-tuberculous mycobacteria, and especially Mycobacterium marinum, we provide a review of the current epidemiology, clinical characteristics, diagnosis and management of Mycobacterium marinum infection.

CRISPR/Cas9-induced asap1a and asap1b co-knockout mutant zebrafish displayed abnormal embryonic development and impaired neutrophil migration

ASAP1 (Arf-GAP with SH3 domain, the ankyrin repeat and the PH domain) is the GTPase activating protein of the small G protein Arf. To understand more about the physiological functions of ASAP1 in vivo, we chose to use the zebrafish as an animal model, and analyzed the characterization of asap1 using loss-of-function studies. Here, two isoforms in zebrafish, asap1a and asap1b, were found to be homologous to human ASAP1, and the gene knockout zebrafish lines for asap1a and asap1b were established using the CRISPR/Cas9 technique with different insertions and deletions of bases. Zebrafish with asap1a and asap1b co-knockout showed a significant reduction in survival and hatching rates, as well as an increase in malformation rates during the early stages of development, while the asap1a or asap1b single knockout mutants did not affect the growth and development of individual zebrafish. Exploring the gene expression compensation between asap1a and asap1b using qRT-PCR, we found that asap1b had increased expression when asap1a was knocked out, showing a clear compensatory effect against asap1a knockout; In turn, asap1a did not have detectable compensating expression after asap1b knockout. Furthermore, the co-knockout homozygous mutants displayed impaired neutrophil migration to Mycobacterium marinum infection, and showed an increased bacterial load. Together, these are the first inherited asap1a and/or asap1b mutant zebrafish lines by the CRISPR/Cas9 gene editing approach, and by serving as useful models, they can significantly contribute to better annotation and follow-up physiological studies of human ASAP1.

Induction of IL-32 in the immune response of keratinocytes to Mycobacterium marinum infection.

Keratinocytes are the predominant cell type in the skin epidermis, and they not only protect the skin from the influence of external physical factors but also function as an immune barrier against microbial invasion. However, little is known regarding the immune defence mechanisms of keratinocytes against mycobacteria. Here, we performed single-cell RNA sequencing (scRNA-seq) on skin biopsy samples from patients with Mycobacterium marinum infection and bulk RNA sequencing (bRNA-seq) on M. marinum-infected keratinocytes in vitro. The combined analysis of scRNA-seq and bRNA-seq data revealed that several genes were upregulated in M. marinum-infected keratinocytes. Further in vitro validation of these genes by quantitative polymerase chain reaction and western blotting assay confirmed the induction of IL-32 in the immune response of keratinocytes to M. marinum infection. Immunohistochemistry also showed the high expression of IL-32 in patients' lesions. These findings suggest that IL-32 induction is a possible mechanism through which keratinocytes defend against M. marinum infection; this could provide new targets for the immunotherapy of chronic cutaneous mycobacterial infections.

A stand-up paddle boarding granuloma.

To the best of our knowledge, this is the only case of a patient with cutaneous Mycobacterium marinum infection associated with stand-up paddle boarding in the Lake District in the UK.

The host-directed therapeutic imatinib mesylate accelerates immune responses to Mycobacterium marinum infection and limits pathology associated with granulomas.

Infections caused by members of the mycobacterium tuberculosis complex [MTC] and nontuberculous mycobacteria [NTM] can induce widespread morbidity and mortality in people. Mycobacterial infections cause both a delayed immune response, which limits rate of bacterial clearance, and formation of granulomas, which contain bacterial spread, but also contribute to lung damage, fibrosis, and morbidity. Granulomas also limit access of antibiotics to bacteria, which may facilitate development of resistance. Bacteria resistant to some or all antibiotics cause significant morbidity and mortality, and newly developed antibiotics readily engender resistance, highlighting the need for new therapeutic approaches. Imatinib mesylate, a cancer drug used to treat chronic myelogenous leukemia [CML] that targets Abl and related tyrosine kinases, is a possible host-directed therapeutic [HDT] for mycobacterial infections, including those causing TB. Here, we use the murine Mycobacterium marinum [Mm] infection model, which induces granulomatous tail lesions. Based on histological measurements, imatinib reduces both lesion size and inflammation of surrounding tissue. Transcriptomic analysis of tail lesions indicates that imatinib induces gene signatures indicative of immune activation and regulation at early time points post infection that resemble those seen at later ones, suggesting that imatinib accelerates but does not substantially alter anti-mycobacterial immune responses. Imatinib likewise induces signatures associated with cell death and promotes survival of bone marrow-derived macrophages [BMDMs] in culture following infection with Mm. Notably, the capacity of imatinib to limit formation and growth of granulomas in vivo and to promote survival of BMDMs in vitro depends upon caspase 8, a key regulator of cell survival and death. These data provide evidence for the utility of imatinib as an HDT for mycobacterial infections in accelerating and regulating immune responses, and limiting pathology associated with granulomas, which may mitigate post-treatment morbidity.

Mycobacterium marinum: A Challenging Cause of Protracted Tenosynovitis

Mycobacterium marinum infections are rare, and they can be difficult to diagnose and treat. This may lead to further spread of the infection and complications, such as tenosynovitis, pyomyositis, and osteomyelitis. A 40-year-old previously healthy man presented with tenosynovitis of the extensor tendons on the second phalanx of his right hand. He was initially treated with steroid injections without any effect. Followingly, ulceration and an abscess developed on the dorsal site of the hand. At this point, it came to the physician's knowledge that the patient had been cleaning an aquarium before onset of symptoms. After progression to massive tenosynovitis, the patient was admitted and underwent multiple surgical debridements. Briefly, after the first surgery, an interferon-γ release assay was positive, and treatment for M. marinum with rifampicin and azithromycin was initiated after eight months of symptoms. Later, a surgical biopsy showed acid-fast bacilli, and a polymerase chain reaction confirmed the diagnosis of M. marinum. In this case story, we highlight the difficulties of diagnosing and managing this complicated infection, describe the considerable morbidity associated with it, and suggest that local tissue concentrations could be useful to improve clinical outcomes, as these concentrations are potentially suboptimal.

Comparative Evaluation of LAMP and Nested PCR for the Rapid Diagnosis of Mycobacterium marinum Infection.

Culture of Mycobacterium marinum is very time-consuming, taking several weeks to produce positive results. Seeking rapid and sensitive diagnostic methods for diagnosis can greatly improve patient treatment. Our study aimed to compare the rapid diagnostic abilities of polymerase chain reaction (PCR), nested PCR and loop mediated isothermal amplification (LAMP) of detecting M. marinum in skin samples from patients with M. marinum infection. A total of 6 M. marinum strains and 6 skin samples with definite diagnosis of M. marinum infection were included in the study. We optimized LAMP performance for detection of M. marinum genomic DNA and confirmed the specificity of the primers. Then, the sensitivity of the LAMP and nested PCR assays were assessed by M. marinum strains and clinical samples. Nested PCR was 10-fold more sensitive than the LAMP assay by serial dilution of M. marinum DNA. PCR positive samples were all positive by LAMP detection of 6 clinical M. marinum strains. Out of 6 clinical skin specimens confirmed as M. marinum infection, 0 (0%), 3 (50%), 3 (50%), and 4 (66.6%) were positive by PCR, nested PCR, LAMP and culture. The LAMP shared the same sensitivity than nested PCR in M. marinum strains and clinical samples, but it was easy to perform and faster than nested PCR assay. Compared with conventional PCR, LAMP and nested PCR are more sensitive and have a higher detection rate of M. marinum in clinical skin specimens. The LAMP assay proved to be more suitable for rapid diagnosis of M. marinum infection in a shorter time, especially in resource-limited settings.

Subungual Hyperkeratosis as a Dermoscopic Clue of Primary Fingernail Mycobacterium Marinum Infections.

Subungual Hyperkeratosis as a Dermoscopic Clue of Primary Fingernail Mycobacterium Marinum Infections.

Abstract 1586: The role of lymphocyte cytosolic protein 1 in a Mycobacterium marinum infection in Danio rerio

Abstract 1586: The role of lymphocyte cytosolic protein 1 in a Mycobacterium marinum infection in Danio rerio

A Murine Mycobacterium marinum Infection Model for Longitudinal Analyses of Disease Development and the Inflammatory Response.

Mycobacterial infections, including tuberculosis, are a major health problem globally. Prevention and treatments of tuberculosis are challenging due to the poor efficacy of the current vaccine and the emergence of drug-resistant strains. Therefore, it is critical to increase our basic understanding of mycobacterial virulence strategies as well as the host immune response during infection in the complex in vivo setting. While existing infection models provide valuable tools for investigating mycobacterial pathogenesis, they also exhibit limitations that can be addressed by the development of complementary models. Here we describe recent advances to the murine Mycobacterium marinum infection model, in which the bacteria produce a local infection restricted to the tail tissue. The M. marinum model has the advantage of mimicking some of the key hallmarks of human tuberculosis not replicated in the conventional murine Mycobacterium tuberculosis model, such as the formation of granulomas with central caseating necrosis and the spontaneous development of a latency-like stage. Moreover, the model is non-lethal and enables longitudinal analysis of disease development in live animals. In this chapter, we report protocols to prepare infected tissue samples for detailed and quantitative analysis of the immune response by flow cytometry, immunofluorescence microscopy, RT-qPCR, ELISA, and Western blot, as well as for the analysis of bacterial load and localization.