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The Journal of Dermatology May 2024
PubMed: 38801177
DOI: 10.1111/1346-8138.17273 -
Journal of the American Veterinary... Dec 2023
Topics: Animals; Oryzias; Fish Diseases
PubMed: 37699544
DOI: 10.2460/javma.23.07.0409 -
MBio Nov 2015Mycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals....
UNLABELLED
Mycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals. M. haemophilum exhibits a unique requirement for iron supplementation to support its growth in culture, but the basis for this property and how it may shape pathogenesis is unclear. Using a combination of Illumina, PacBio, and Sanger sequencing, the complete genome sequence of M. haemophilum was determined. Guided by this sequence, experiments were performed to define the basis for the unique growth requirements of M. haemophilum. We found that M. haemophilum, unlike many other mycobacteria, is unable to synthesize iron-binding siderophores known as mycobactins or to utilize ferri-mycobactins to support growth. These differences correlate with the absence of genes associated with mycobactin synthesis, secretion, and uptake. In agreement with the ability of heme to promote growth, we identified genes encoding heme uptake machinery. Consistent with its propensity to infect the skin, we show at the whole-genome level the genetic closeness of M. haemophilum with Mycobacterium leprae, an organism which cannot be cultivated in vitro, and we identify genes uniquely shared by these organisms. Finally, we identify means to express foreign genes in M. haemophilum. These data explain the unique culture requirements for this important pathogen, provide a foundation upon which the genome sequence can be exploited to improve diagnostics and therapeutics, and suggest use of M. haemophilum as a tool to elucidate functions of genes shared with M. leprae.
IMPORTANCE
Mycobacterium haemophilum is an emerging pathogen with an unknown natural reservoir that exhibits unique requirements for iron supplementation to grow in vitro. Understanding the basis for this iron requirement is important because it is fundamental to isolation of the organism from clinical samples and environmental sources. Defining the molecular basis for M. haemophilium's growth requirements will also shed new light on mycobacterial strategies to acquire iron and can be exploited to define how differences in such strategies influence pathogenesis. Here, through a combination of sequencing and experimental approaches, we explain the basis for the iron requirement. We further demonstrate the genetic closeness of M. haemophilum and Mycobacterium leprae, the causative agent of leprosy which cannot be cultured in vitro, and we demonstrate methods to genetically manipulate M. haemophilum. These findings pave the way for the use of M. haemophilum as a model to elucidate functions of genes shared with M. leprae.
Topics: Base Sequence; Culture Media; Genome, Bacterial; Heme; Hemoglobins; Humans; Iron; Mycobacterium haemophilum; Mycobacterium leprae; Oxazoles; Phenotype; Sequence Analysis, DNA
PubMed: 26578674
DOI: 10.1128/mBio.01313-15 -
International Journal of STD & AIDS Nov 2015We report a case of disseminated Mycobacterium haemophilum osteomyelitis in a patient with advanced HIV infection, who later developed recurrent immune reconstitution... (Review)
Review
We report a case of disseminated Mycobacterium haemophilum osteomyelitis in a patient with advanced HIV infection, who later developed recurrent immune reconstitution inflammatory syndrome after commencement of antiretroviral therapy. We review previous reports of M. haemophilum bone and joint infection associated with HIV infection and describe the management of M. haemophilum-associated immune reconstitution inflammatory syndrome, including the role of surgery as an adjunctive treatment modality and the potential drug interactions between antiretroviral and antimycobacterial agents.
Topics: AIDS-Related Opportunistic Infections; Adult; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Debridement; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Magnetic Resonance Imaging; Male; Middle Aged; Mycobacterium Infections; Mycobacterium haemophilum; Osteomyelitis; Polymerase Chain Reaction; Tenosynovitis
PubMed: 25577597
DOI: 10.1177/0956462414565403 -
International Journal of Dermatology Feb 2024Mycobacterium haemophilum has been increasingly found in severely immunocompromised patients but is scarcely reported in immunocompetent adults. (Review)
Review
BACKGROUND
Mycobacterium haemophilum has been increasingly found in severely immunocompromised patients but is scarcely reported in immunocompetent adults.
METHODS
We systematically reviewed previous literature to identify studies on infection in immunocompetent adults. Articles reporting at least one case of M. haemophilum infection were included. We excluded articles involving patients who had immunosuppression-related diseases and routinely used glucocorticoids or immunosuppressants. We also reported a case of a young immunocompetent woman infected by M. haemophilum along the eyebrows, which was probably due to the use of an eyebrow pencil retrieved from a sink drain.
RESULTS
Twelve qualifying articles reporting M. haemophilum infection in immunocompetent adults were identified. Among them, most cases report skin lesions along the eyebrows, and the remaining had cervicofacial lymphadenitis, lesions on the arm or fingers, inflammation in the eyeballs, or ulceration in the perineal region. Most cases were caused by tattoos, make-up, injury, or surgical operation. For diagnosis, specialized tissue culture sensitivity was roughly 75%, and polymerase chain reaction (PCR) test sensitivity was approximately 89%. Triple antibiotic therapy for 3 to 24 months, or surgical excision was effective in controlling infection.
CONCLUSION
M. haemophilum infection should be considered if routine antibacterial and glucocorticoid treatments are ineffective against the disease, even in healthy adults. To definitively diagnose this infection, conditioned tissue culture or PCR testing is required. Treatment usually involves a combination of multiple antibiotics and, if necessary, surgical removal of infected tissue.
Topics: Adult; Female; Humans; Mycobacterium haemophilum; Anti-Bacterial Agents; Lymphadenitis; Mycobacterium Infections; Inflammation
PubMed: 38058233
DOI: 10.1111/ijd.16874 -
BMC Infectious Diseases Jan 2021Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive... (Review)
Review
BACKGROUND
Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib.
CASE PRESENTATION
A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired.
CONCLUSIONS
This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.
Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Cellulitis; Coinfection; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Fungemia; Humans; Male; Mycobacterium Infections; Mycobacterium haemophilum; Nitriles; Opportunistic Infections; Primary Myelofibrosis; Pyrazoles; Pyrimidines
PubMed: 33413168
DOI: 10.1186/s12879-020-05703-2 -
Veterinary Clinical Pathology Jun 2023A 4-year-old female spayed Australian cattle dog was presented to the Emergency Service at the University of Missouri Veterinary Health Center Small Animal Hospital for...
A 4-year-old female spayed Australian cattle dog was presented to the Emergency Service at the University of Missouri Veterinary Health Center Small Animal Hospital for generalized pain and lethargy. At presentation, the dog showed severe cervical spinal pain and thoracic limb deficits consistent with a multifocal neuroanatomic localization. Magnetic resonance imaging of the cervical spine revealed T2 and T1 postcontrast intense signal extending from the level of the medulla through C5 most marked in the caudal brainstem and cranial cervical spinal cord. The suspected diagnosis was severe meningoencephalomyelitis and secondary edema. Analysis of cerebrospinal fluid (CSF) collected from the cerebellomedullary cistern revealed a marked mixed pleocytosis with intralesional structures morphologically consistent with Mycobacterium sp. Standard DNA PCR assay performed on the CSF yielded the presence of Mycobacterium haemophilum. To the authors' knowledge, this is the first reported case of CNS mycobacteriosis diagnosed on CSF analysis in a dog.
Topics: Female; Cattle; Dogs; Animals; Mycobacterium haemophilum; Australia; Spinal Cord; Magnetic Resonance Imaging; Leukocytosis; Dog Diseases; Cerebrospinal Fluid; Cattle Diseases
PubMed: 36931892
DOI: 10.1111/vcp.13206 -
Infectious Diseases (London, England) Jul 2023is a nontuberculous mycobacterium with fastidious growth requirements and an increasingly reported cause of extrapulmonary disease. Timely diagnosis and management of...
BACKGROUND
is a nontuberculous mycobacterium with fastidious growth requirements and an increasingly reported cause of extrapulmonary disease. Timely diagnosis and management of infections and the immune reconstitution inflammatory syndromes (IRIS) observed in a subset of patients during treatment remain challenging.
METHODS
We conducted a retrospective chart review between January 1, 2010, and January 1, 2022 and identified 26 patients diagnosed with infection at our institution. We describe their clinical presentation, diagnostic results, management, and outcomes.
RESULTS
The majority of patients in our cohort had upper and/or lower extremity skin involvement, were immunosuppressed, and had generally favourable treatment outcomes. All tested isolates were susceptible to clarithromycin and trimethoprim-sulfamethoxazole. Moreover, high rates of susceptibility were noted for ciprofloxacin (95%), linezolid (90%), and rifampin (85%). IRIS was identified in 31% of cases and should be considered in patients who develop worsening skin lesions or systemic symptoms following the initiation of effective antimicrobial therapy. Visualisation of acid-fast bacilli on initial tissue stains, a positive mycobacterial blood culture, and rapid de-escalation of tumour necrosis factor-α inhibitors and/or corticosteroids were more frequently encountered among patients in our cohort who developed IRIS.
CONCLUSION
infection should be considered among patients receiving immunomodulatory therapy who develop discoloured or nodular skin lesions involving the extremities, worsening focal arthritis, tenosynovitis, or isolated adenopathy. A heightened awareness of this pathogen's clinical and laboratory characteristics can lead to a timely diagnosis and favourable outcome.
Topics: Humans; Immune Reconstitution Inflammatory Syndrome; Mycobacterium haemophilum; Mycobacterium Infections; Retrospective Studies; Treatment Outcome
PubMed: 37151046
DOI: 10.1080/23744235.2023.2208210 -
Journal of Fish Diseases Jun 2020The use of zebrafish (Danio rerio) in biomedical research has expanded at a tremendous rate over the last two decades. Along with increases in laboratories using this... (Review)
Review
The use of zebrafish (Danio rerio) in biomedical research has expanded at a tremendous rate over the last two decades. Along with increases in laboratories using this model, we are discovering new and important diseases. We review here the important pathogens and diseases based on some 20 years of research and findings from our diagnostic service at the NIH-funded Zebrafish International Resource Center. Descriptions of the present status of biosecurity programmes and diagnostic and treatment approaches are included. The most common and important diseases and pathogens are two parasites, Pseudoloma neurophilia and Pseudocapillaria tomentosa, and mycobacteriosis caused by Mycobacterium chelonae, M. marinum and M. haemophilum. Less common but deadly diseases are caused by Edwardsiella ictaluri and infectious spleen and kidney necrosis virus (ISKNV). Hepatic megalocytosis and egg-associated inflammation and fibroplasia are common, apparently non-infectious, in zebrafish laboratories. Water quality diseases include supersaturation and nephrocalcinosis. Common neoplasms are spindle cell sarcomas, ultimobranchial tumours, spermatocytic seminomas and a small-cell carcinoma that is caused by a transmissible agent. Despite the clear biosecurity risk, researchers continue to use fish from pet stores, and here, we document two novel coccidia associated with significant lesions in zebrafish from one of these stores.
Topics: Animals; Animals, Laboratory; Communicable Disease Control; Fish Diseases; Oregon; Research; Zebrafish
PubMed: 32291793
DOI: 10.1111/jfd.13165 -
Journal Der Deutschen Dermatologischen... Nov 2023
Review
[Hautbeteiligung bei Infektionen mit Mycobacterium haemophilum: Zwei Fallberichte und eine aktualisierte Literaturübersicht: Mycobacterium haemophilum infection with cutaneous involvement: Two case reports and an updated literature review].
PubMed: 37946643
DOI: 10.1111/ddg.15163_g