Proposal of Sphingobacterium allocomposti nom. nov., Mycobacterium chelonae subsp. bovistauri nom. nov. and Lactobacillus delbrueckii subsp. allosunkii nom. nov. as new names with replacement specific or subspecific epithets, respectively, for three illegitimate prokaryotic names Sphingobacterium composti Yoo et al. 2007, Mycobacterium chelonae subsp. bovis Kim et al. 2017 and Lactobacillus delbrueckii subsp. sunkii Kudo et al. 2012; proposal of Christiangramia oceanisediminis comb. nov. and Christiangramia crocea comb. nov. as replacement names respectively for two illegitimate prokaryotic names Gramella oceanisediminis Yang et al. 2023 and Gramella crocea Zhang et al. 2023.

As required by Rule 54 of the International Code of Nomenclature of Prokaryotes, the authors propose the replacement specific epithet 'allocomposti' for the illegitimate prokaryotic name Sphingobacterium composti Yoo et al. 2007, the replacement subspecific epithet 'bovistauri' for Mycobacterium chelonae subsp. bovis Kim et al. 2017 and the replacement subspecific epithet 'allosunkii' for Lactobacillus delbrueckii subsp. sunkii Kudo et al. 2012. Meanwhile, new combinations Christiangramia oceanisediminis and Christiangramia crocea are also proposed as replacements for the illegitimate prokaryotic names Gramella oceanisediminis Yang et al. 2023 and Gramella crocea Zhang et al. 2023, respectively.

Common Features of Environmental Mycobacterium chelonae from Colorado Using Partial and Whole Genomic Sequence Analyses.

Nontuberculous mycobacteria (NTM) are environmentally acquired opportunistic pathogens that cause chronic lung disease in susceptible individuals. While presumed to be ubiquitous in built and natural environments, NTM environmental studies are limited. While environmental sampling campaigns have been performed in geographic areas of high NTM disease burden, NTM species diversity is less defined among areas of lower disease burden like Colorado. In Colorado, metals such as molybdenum have been correlated with increased risk for NTM infection, yet environmental NTM species diversity has not yet been widely studied. Based on prior regression modeling, three areas of predicted high, moderate, and low NTM risk were identified for environmental sampling in Colorado. Ice, plumbing biofilms, and sink tap water samples were collected from publicly accessible freshwater sources. All samples were microbiologically cultured and NTM were identified using partial rpoB gene sequencing. From these samples, areas of moderate risk were more likely to be NTM positive. NTM recovery from ice was more common than recovery from plumbing biofilms or tap water. Overall, nine different NTM species were identified, including clinically important Mycobacterium chelonae. MinION technology was used to whole genome sequence and compare mutational differences between six M. chelonae genomes, representing three environmental isolates from this study and three other M. chelonae isolates from other sources. Drug resistance genes and prophages were common findings among environmentally derived M. chelonae, promoting the need for expanded environmental sampling campaigns to improve our current understanding of NTM species abundance while opening new avenues for improved targeted drug therapies.

Emergence of Inducible Macrolide Resistance in Mycobacterium chelonae Due to Broad-Host-Range Plasmid and Chromosomal Variants of the Novel 23S rRNA Methylase Gene, erm(55).

Macrolides are a mainstay of therapy for infections due to nontuberculous mycobacteria (NTM). Among rapidly growing mycobacteria (RGM), inducible macrolide resistance is associated with four chromosomal 23S rRNA methylase (erm) genes. Beginning in 2018, we detected high-level inducible clarithromycin resistance (MICs of ≥16µg/mL) in clinical isolates of Mycobacterium chelonae, an RGM species not previously known to contain erm genes. Using whole-genome sequencing, we identified a novel plasmid-mediated erm gene. This gene, designated erm(55)P, exhibits <65% amino acid identity to previously described RGM erm genes. Two additional chromosomal erm(55) alleles, with sequence identities of 81% to 86% to erm(55)P, were also identified and designated erm(55)C and erm(55)T. The erm(55)T is part of a transposon. The erm(55)P allele variant is located on a putative 137-kb conjugative plasmid, pMchErm55. Evaluation of 133 consecutive isolates from 2020 to 2022 revealed 5 (3.8%) with erm(55). The erm(55)P gene was also identified in public data sets of two emerging pathogenic pigmented RGM species: Mycobacterium iranicum and Mycobacterium obuense, dating back to 2008. In both species, the gene appeared to be present on plasmids homologous to pMchErm55. Plasmid-mediated macrolide resistance, not described previously for any NTM species, appears to have spread to multiple RGM species. This has important implications for antimicrobial susceptibility guidelines and treatment of RGM infections. Further spread could present serious consequences for treatment of other macrolide-susceptible RGM. Additional studies are needed to determine the transmissibility of pMchErm55 and the distribution of erm(55) among other RGM species.

Plasmid-mediated drug resistance in mycobacteria: the tip of the iceberg?

Macrolides, such as clarithromycin, are crucial in the treatment of nontuberculous mycobacteria (NTM). NTM are notoriously innately drug resistant, which has made the dependence on macrolides for their treatment even more important. Not surprisingly, resistance to macrolides has been documented in some NTM, including Mycobacterium avium and Mycobacterium abscessus, which are the two NTM species most often identified in clinical isolates. Resistance is mediated by point mutations in the 23S ribosomal RNA or by methylation of the rRNA by a methylase (encoded by an erm gene). Chromosomally encoded erm genes have been identified in many of the macrolide-resistant isolates, but not in Mycobacterium chelonae. Now, Brown-Elliott et al. (J Clin Microbiol 61:e00428-23, 2023, https://doi.org/10.1128/JCM.00428-23) describe the identification of a new erm variant, erm(55), which was found either on the chromosome or on a plasmid in highly macrolide-resistant clinical isolates of M. chelonae. The chromosomal erm(55) gene appears to be associated with mobile elements; one gene is within a putative transposon and the second is in a large (37 kb) insertion/deletion. The plasmid carrying erm(55) also encodes type IV and type VII secretion systems, which are often linked on large mycobacterial plasmids and are hypothesized to mediate plasmid transfer. While the conjugative transfer of the erm(55)-containing plasmid between NTM has yet to be demonstrated, the inferences are clear, as evidenced by the dissemination of plasmid-mediated drug resistance in other medically important bacteria. Here, we discuss the findings of Brown-Elliott et al., and the potential ramifications on treatment of NTM infections.

Rare, Atypical Mycobacterium Infection of the Hand in Immunocompetent Individuals.

We present two cases of immunocompetent individuals diagnosed with nontuberculous infections of the hand caused by organisms rarely seen in the clinical setting: Mycobacterium heckeshornense and Mycobacterium chelonae. In the first case, a 50-year-old male presented with tenosynovitis of left long finger. He was subsequently found to have a Mycobacterium heckeshornense infection that was resolved with multiple surgeries and a long-term regimen of several antibiotics. The second case was a 29-year-old female with a history of a trivial hand injury infected with Mycobacterium chelonae. She was successfully treated with surgical debridement and antibiotics over the course of eight months. It is important to recognize the increasing prevalence of these two species of bacteria as human pathogens that can result in infections of the extremities even in immunocompetent individuals. (Journal of Surgical Orthopaedic Advances 32(1):055-058, 2023).

Differences in susceptibility to Mycobacterium chelonae in zebrafish (Danio rerio) lines commonly used in scientific research.

Mycobacteriosis is one of the most common diseases encountered in laboratory zebrafish. These infections can present a problem to researchers using zebrafish because they may introduce unknown experimental variables. Whilst differences in severity of infections between species of Mycobacterium infecting zebrafish have been well documented, little is known about differences in susceptibility between zebrafish lines. Previous surveys have found higher prevalence in the TU zebrafish line relative to other lines, suggesting that there may be underlying genetic differences in susceptibility. This study investigates Mycobacterium chelonae H1E2-GFP infections in four different zebrafish lines commonly used in research (AB, 5D, casper and TU). Fish were exposed to a labelled (green-fluorescent protein (GFP)) strain of M. chelonae by intraperitoneal injection, and infection status was evaluated after 10 weeks. Visualization of GFP in euthanized fish and histology were used as endpoints. In GFP images, severity was assessed by image analysis, and in histological sections, counts of granulomas containing acid-fast bacteria were used. Results indicated differences in severity of infections between lines, but no significant differences in prevalence.

Increased whiB7 expression and antibiotic resistance in Mycobacterium chelonae carrying two prophages.

BACKGROUND: The global rise in the incidence of non-tuberculosis mycobacterial infections is of increasing concern due their high levels of intrinsic antibiotic resistance. Although integrated viral genomes, called prophage, are linked to increased antibiotic resistance in some bacterial species, we know little of their role in mycobacterial drug resistance. RESULTS: We present here for the first time, evidence of increased antibiotic resistance and expression of intrinsic antibiotic resistance genes in a strain of Mycobacterium chelonae carrying prophage. Strains carrying the prophage McProf demonstrated increased resistance to amikacin. Resistance in these strains was further enhanced by exposure to sub-inhibitory concentrations of the antibiotic, acivicin, or by the presence of a second prophage, BPs. Increased expression of the virulence gene, whiB7, was observed in strains carrying both prophages, BPs and McProf, relative to strains carrying a single prophage or no prophages. CONCLUSIONS: This study provides evidence that prophage alter expression of important mycobacterial intrinsic antibiotic resistance genes and additionally offers insight into the role prophage may play in mycobacterial adaptation to stress.

Small vessel vasculitis secondary to Mycobacterium chelonae.

Mycobacterial infection can be seriously debilitating and challenging to diagnose. The infection can mimic vasculitis associated with positive anti-neutrophilic cytoplasmic autoantibodies (ANCA). This clinical scenario is exemplified with a well-studied case of a 63-year-old Caucasian man with uncontrolled diabetes and ulcerative colitis on immunosuppressive agents. The patient was hospitalized for 3 months with worsening painful hand ulcerations. Primary vasculitis was first suspected, but the patient was later diagnosed with vasculitis secondary to Mycobacterium chelonae infection. Report includes discussion on sequence of testing which led to the diagnosis. After proper diagnosis and change to proper antibiotics, the patient's vasculitis improved over time. It is our hope that this report further raises awareness of mycobacterial infection as a mimicker of vasculitis. We also provide a review of relevant literature on non-tuberculosis mycobacterial (NTM) infection including a review of 22 articles and 12 cases found in the literature. The salient features of the literature review include that 10 of the 12 cases were patients who had risk factors of immunosuppression due to medications, and all patients were infected by mycobacterium causing skin vasculitis. After given the proper directed antibiotic treatment, 11 of the 12 patients had a reported improved outcome.

A Complication of Mycobacterium chelonae Infection Following Orbital Floor Fracture Repair.

ABSTRACT: Mycobacterium chelonae is a rare, atypical nontuberculous bacterium that has been reported to be an underlying cause of persistent wound infections. Although there are several studies highlighting the role of M chelonae as the putative cause of other postoperative wound infections, to our knowledge there are no reports of infection following implant placement for repair of an orbital floor fracture. The authors present a unique case describing the management of a persistent postoperative infection in a young, immunocompetent patient with an orbital floor fracture repaired with a Stryker Medpor Titan implant. The patient was initially treated with broad-spectrum antibiotics with minimal clinical improvement. Following culture-proven M chelonae, a second surgical intervention was undertaken to remove the implant and later, a third intervention for scar revision. The patient has remained free of infection utilizing a long-term tailored 2-drug antibiotic regimen. This case emphasizes the need for recognition of M chelonae as a potential pathogen in certain clinical situations and the difficulty in eradicating M chelonae in the context of infected implantable devices. The comprehensive treatment protocol required to ensure adequate therapy is reviewed.

Mycobacterium chelonae Infection Identified by Metagenomic Next-Generation Sequencing as the Probable Cause of Acute Contained Rupture of a Biological Composite Graft-A Case Report.

We present the case of a 72-year-old female patient with acute contained rupture of a biological composite graft, 21 months after replacement of the aortic valve and the ascending aorta due to an aortic dissection. Auramine-rhodamine staining of intraoperative biopsies showed acid-fast bacilli, but classical culture and molecular methods failed to identify any organism. Metagenomic analysis indicated infection with Mycobacterium chelonae, which was confirmed by target-specific qPCR. The complexity of the sample required a customized bioinformatics pipeline, including cleaning steps to remove sequences of human, bovine ad pig origin. Our study underlines the importance of multiple testing to increase the likelihood of pathogen identification in highly complex samples.

Diagnosis of Mycobacterium abscessus/chelonae complex cutaneous infection: Correlation of tissue culture and skin biopsy.

Mycobacterium abscessus and M. chelonae belong to the rapid-growing nontuberculous mycobacteria (NTM) group, which are defined by their ability to form visible colonies on agar within 7 days of subculture. Cutaneous infections by this complex show a heterogeneous clinical presentation with varied histopathologic findings. However, the presence of vacuoles in many specimens has been reported as a specific histologic finding. Herein, we correlate the histopathology of patients with tissue-culture positive M. abscessus/M. chelonae complex in order to identify features that may prompt a rapid categorization of the infectious etiology. The cohort includes 33 skin punch biopsy specimens from 28 patients who had associated positive tissue cultures. The most frequent clinical presentation was a single or multiple nodule. Twenty-seven specimens (81.81%) were found to have vacuoles. The observation of certain histologic features (ie, polymorphonuclear microabscesses and epithelioid granuloma formation) should raise the possibility of infection by NTM. In addition to these findings, we believe the presence of vacuoles in the dermal and subcutaneous inflammation should raise suspicion for NTM.

Mycobacterium chelonae bloodstream infection induced by osteomyelitis of toe: A case report.

Mycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BACTEC™ FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient.

Case Series and Review of the Literature of Mycobacterium chelonae Infections of the Lower Extremities.

Mycobacterium chelonae infections involving the lower extremities are rare clinical entities that present a diagnostic challenge given its diverse clinical presentations ranging from superficial (e.g., cellulitis, painful vesicular lesions) to deep (e.g., tenosynovitis) infections. We present 1 cases of M chelonae infections of the feet diagnosed 6 to 12 months after initial symptoms representing the difficulty of diagnosing this condition. Both cases were successfully managed with aggressive surgical debridement and long durations of antibiotic therapy with long-term care. A comprehensive review of the literature of M chelonae infections of the lower extremities was performed to provide summary data on the presenting symptoms, examination findings, predisposing conditions, and management approaches of this rare, but emerging clinical entity. Our cases and comprehensive review serve to raise awareness of atypical mycobacterial infections, including M chelonae, and advocate for the early consideration of mycobacterial cultures in the diagnostic workup of chronic lower extremity infections especially in the setting of poor initial response to standard antibacterial therapies.

Infectious Tenosynovitis of the Tibialis Anterior Due to Mycobacterium chelonae After Intravenous Heroin Injection.

Mycobacterium chelonae is a ubiquitous Gram-positive, acid-fast, non-spore-forming bacterium commonly encountered in nature associated with aquatic animals, soil, and water, including tap water. Nontuberculous mycobacterial tenosynovitis infections caused by M. chelonae in the lower extremity are uncommon, leading to a paucity of literature documenting the diagnosis and treatment of such cases. This report is of a 65-year-old male patient who was found to have an M. chelonae infection along the tibialis anterior tendon after injecting himself with heroin into the dorsal foot veins. This review covers the diagnosis and treatment as well as a case report on the outcome of infectious tenosynovitis of the tibialis anterior associated with M. chelonae. To date, this is the only reported case of tibialis anterior infectious tenosynovitis caused by M. chelonae after intravenous heroin injection.

Corynebacterium kroppenstedtii as a pathogen of a Jones tube infection following conjunctivo-dacryocystorhinostomy.

A 35-year-old woman complained of an unpleasant odor for a few days after a change in foundation cream. The patient had previously undergone conjunctivo-dacryocystorhinostomy with a Jones tube fixed with non-absorbable suture. Slit-lamp examination revealed an orange-colored discharge in the tube. A culture test of the discharge showed Corynebacterium kroppenstedtii (1+), Aspergillus versicolor (1+), and Mycobacterium chelonae (1+). After medical treatment and suture removal, the discharge completely disappeared. This is the first reported case of a Jones tube infection following conjunctivo-dacryocystorhinostomy with multiple microorganisms, including C. kroppenstedtii.

In Vitro Activities of Omadacycline against Rapidly Growing Mycobacteria.

The in vitro activity of omadacycline, a new tetracycline derivative, was evaluated against isolates of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum using a broth microtiter dilution assay. Omadacycline had MIC90 values of 2 µg/ml, 0.25 µg/ml, and 0.5 µg/ml, respectively. The in vitro activity of omadacycline against rapidly growing mycobacteria indicates that it may have the potential to improve therapy for infections caused by these organisms.

Skin and Soft Tissue Infections Caused by Mycobacterium chelonae: More Common Than Expected?

Mycobacterium chelonae is a rapidly growing non-tuberculous mycobacterium, which causes infections of the human skin and soft tissue. Despite an increasing incidence of such infections, patients are often misdiagnosed. We report here 5 patients with cutaneous and/or soft tissue infection due to M. chelonae who were diagnosed and treated at our centre. Two of the 5 patients were on immunosuppressive treatment. While clinical presentations differed in each patient, all had a long history of skin lesions. In addition to careful history-taking, tissue biopsies were obtained for mycobacterial culture and histopathological examination. Culture-directed antibiotic therapy was initiated, which resulted in a slow, but continuous, healing of the lesions. In summary, M. chelonae infections are still relatively rare, but should be considered in both immunocompromised and immunocompetent patients with prolonged skin lesions resistant to standard antibiotic treatment. For diagnosis, tissue analysis for mycobacterial culture and histopathological examination, and once diagnosed, adequate antibiotic treatment, is needed.

Transmission of Mycobacterium chelonae and Mycobacterium marinum in laboratory zebrafish through live feeds.

The zebrafish (Danio rerio) is a popular vertebrate model organism used in a wide range of research fields. Mycobacteriosis, caused by Mycobacterium species, is particularly concerning because it is a common disease associated with chronic infections in these fish. Infections are also a source of uncontrolled experimental variance that may influence research results. Live feeds for zebrafish are common and include paramecia (Paramecium caudatum), brine shrimp (Artemia franciscana) and rotifers (Branchionus spp.). Although nutritionally beneficial, live feeds may pose a biosecurity risk. In this study, we investigate transmission of Mycobacterium chelonae and Mycobacterium marinum through these three live feeds. We show that all three live feeds ingest both M. marinum and M. chelonae and can transmit mycobacterial infections to zebrafish. This observation emphasizes the need for live feeds to be included in the consideration of potential biosecurity risks. This study is of importance to other beyond the zebrafish community, including those of additional aquatic models and those using live feeds for other types of aquaculture.

A case of Mycobacterium chelonae mediastinitis and acute humoral rejection after heart transplantation.

Mediastinitis is one of the life-threating complications that can occur after cardiac surgery. However, to the best of our knowledge, there has been no report of mediastinitis caused by Mycobacterium chelonae, which is one of the rapidly growing nontuberculous mycobacteria species. As far as we know, our case is the first case describing the curative management for mediastinitis caused by M. chelonae after heart transplantation.

Non-tuberculous Mycobacterium species causing mycobacteriosis in farmed aquatic animals of South Africa.

BACKGROUND: Mycobacteriosis caused by non-tuberculous mycobacteria (NTM), is among the most chronic diseases of aquatic animals. In addition, fish mycobacteriosis has substantial economic consequences especially in the aquaculture and fisheries industry as infections may significantly decrease production and trade. Some fish NTM pathogens are highly virulent and zoonotic; as such, infection of aquaria with these pathogens is a public health concern. In this study, we report isolation of nine different NTM species from sixteen aquatic animals including different fish species, frogs and a crocodile. Given the clinical significance of Mycobacterium marinum and its close relation to Mycobacterium tuberculosis, as well as the significance of ESAT 6 and CFP-10 secretion in mycobacterial virulence, we analysed the esxA and esxB nucleotide sequences of M. marinum isolates identified in this study as well as other mycobacteria in the public databases. RESULTS: Mycobacterium shimoidei, Mycobacterium marinum, Mycobacterium chelonae, Mycobacterium septicum /M. peregrinum and Mycobacterium porcinum were isolated from gold fish, Guppy, exotic fish species in South Africa, koi and undefined fish, Knysna seahorse, as well Natal ghost frogs respectively, presenting tuberculosis like granuloma. Other NTM species were isolated from the studied aquatic animals without any visible lesions, and these include Mycobacterium sp. N845 T, Mycobacterium fortuitum, a member of the Mycobacterium avium complex, and Mycobacterium szulgai. Phylogenetic analysis of mycobacteria, based on esxA and esxB genes, separated slow growing from rapidly growing mycobacteria as well as pathogenic from non-pathogenic mycobacteria in some cases. CONCLUSIONS: Isolation of the different NTM species from samples presenting granuloma suggests the significance of these NTM species in causing mycobacteriosis in these aquatic animals. The study also revealed the potential of esxA and esxB sequences as markers for phylogenetic classification of mycobacteria. Observations regarding use of esxA and esxB sequences for prediction of potential pathogenicity of mycobacteria warrants further investigation of these two genes in a study employing NTM species with well-defined pathogenicity.