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"Mycobacterium tilburgii," a newly described, uncultivated opportunistic pathogen.

ABSTRACT: Molecular methods are increasingly used to identify pathogens that are difficult to cultivate. We report a case of disseminated infection with "Mycobacterium tilburgii," a proposed species that has never been cultivated. The case illustrates the diagnostic utility of sequence analysis of the 16S rRNA gene directly from clinical specimens.

SUBMITTER: Palmore TN

PROVIDER: S-EPMC2681830 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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"Mycobacterium tilburgii," a newly described, uncultivated opportunistic pathogen.

Palmore Tara N TN Shea Yvonne R YR Conville Patricia S PS Witebsky Frank G FG Anderson Victoria L VL Rupp Hodge Irene P IP Holland Steven M SM

Journal of clinical microbiology 20090304 5

Molecular methods are increasingly used to identify pathogens that are difficult to cultivate. We report a case of disseminated infection with "Mycobacterium tilburgii," a proposed species that has never been cultivated. The case illustrates the diagnostic utility of sequence analysis of the 16S rRNA gene directly from clinical specimens. ...[more]

PMID: 19261797

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"Mycobacterium tilburgii" infections.

Project description: Not available

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Whole-Genome Sequencing of Mycobacterium tilburgii Strain MEPHI.

Project description:Mycobacterium tilburgii is a fastidious mycobacterium which has previously been reported to cause severe disseminated infections. Genome sequencing of the M. tilburgii MEPHI clinical isolate yielded 3.14 Mb, with 66.3% GC content, and confirmed phylogenetic placement within the Mycobacterium simiae complex.

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Deciphering the virulence factors of the opportunistic pathogen Mycobacterium colombiense.

Project description:Mycobacterium avium complex (MAC) contains clinically important nontuberculous mycobacteria worldwide and is the second largest medical complex in the Mycobacterium genus after the Mycobacterium tuberculosis complex. MAC comprises several species that are closely phylogenetically related but diverse regarding their host preference, course of disease, virulence and immune response. In this study we provided immunologic and virulence-related insights into the M. colombiense genome as a model of an opportunistic pathogen in the MAC. By using bioinformatic tools we found that M. colombiense has deletions in the genes involved in p-HBA/PDIM/PGL, PLC, SL-1 and HspX production, and loss of the ESX-1 locus. This information not only sheds light on our understanding the virulence mechanisms used by opportunistic MAC pathogens but also has great potential for the designing of species-specific diagnostic tools.

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Disseminated infection with Mycobacterium tilburgii in a male immunocompromised patient.

Project description:Mycobacterium tilburgii is a nonculturable nontuberculous mycobacterium identifiable only by molecular methods. We report a case of disseminated M. tilburgii infection illustrating the importance of 16S rRNA gene sequencing to determine the responsible mycobacterial pathogen and the difficulties in tailoring antimycobacterial treatment in the absence of a culturable organism.

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Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus.

Project description:BackgroundMycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its intrinsic polyresistance to a wide range of antibiotics, most treatments for M. abscessus pulmonary infections are poorly effective. In this context, antimicrobial peptides (AMPs) active against bacterial strains and less prompt to cause resistance, represent a good alternative to conventional antibiotics. Herein, we evaluated the effect of three arenicin isoforms, possessing two or four Cysteines involved in one (Ar-1, Ar-2) or two disulfide bonds (Ar-3), on the in vitro growth of M. abscessus.MethodsThe respective disulfide-free AMPs, were built by replacing the Cysteines with alpha-amino-n-butyric acid (Abu) residue. We evaluated the efficiency of the eight arenicin derivatives through their antimicrobial activity against M. abscessus strains, their cytotoxicity towards human cell lines, and their hemolytic activity on human erythrocytes. The mechanism of action of the Ar-1 peptide was further investigated through membrane permeabilization assay, electron microscopy, lipid insertion assay via surface pressure measurement, and the induction of resistance assay.ResultsOur results demonstrated that Ar-1 was the safest peptide with no toxicity towards human cells and no hemolytic activity, and the most active against M. abscessus growth. Ar-1 acts by insertion into mycobacterial lipids, resulting in a rapid membranolytic effect that kills M. abscessus without induction of resistance.ConclusionOverall, the present study emphasized Ar-1 as a potential new alternative to conventional antibiotics in the treatment of CF-associated bacterial infection related to M. abscessus.

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The recombination-cold region as an epidemiological marker of recombinogenic opportunistic pathogen Mycobacterium avium.

Project description:BACKGROUND:The rapid identification of lineage remains a challenge in the genotyping of clinical isolates of recombinogenic pathogens. The chromosome of Mycobacterium avium subsp. hominissuis (MAH), an agent of Mycobacterium avium complex (MAC) lung disease, is often mosaic and is composed of chromosomal segments originating from different lineages. This makes it difficult to infer the MAH lineage in a simple experimental set-up. To overcome this difficulty, we sought to identify chromosomal marker genes containing lineage-specific alleles by genome data mining. RESULTS:We conducted genetic population structure analysis, phylogenetic analysis, and a survey of historical recombination using data from 125 global MAH isolates. Six MAH lineages (EA1, EA2, SC1, SC2, SC3, and SC4) were identified in the current dataset. One P-450 gene (locus_tag MAH_0788/MAV_0940) in the recombination-cold region was found to have multiple alleles that could discriminate five lineages. By combining the information about allele type from one additional gene, the six MAH lineages as well as other M. avium subspecies were distinguishable. A recombination-cold region of 116 kb contains an insertion hotspot and is flanked by a mammalian cell-entry protein operon where allelic variants have previously been reported to occur. Hence, we speculate that the acquisition of lineage- or strain-specific insertions has introduced homology breaks in the chromosome, thereby reducing the chance of interlineage recombination. CONCLUSIONS:The allele types of the newly identified marker genes can be used to predict major lineages of M. avium. The single nucleotide polymorphism typing approach targeting multiallelic loci in recombination-cold regions will facilitate the epidemiological study of MAC, and may also be useful for equivalent studies of other nontuberculous mycobacteria potentially carrying mosaic genomes.

| S-EPMC6798384 | biostudies-literature

Nonsense suppression as a mechanism of genetic complemtation in the opportunistic pathogen Mycobacterium marinum

Project description:Here, we report the discovery of a novel mechanism of genetic complementation in M. marinum. We found that nonsense suppression was causing genetic complementation. Nonsense suppression was linked to alterations in cell permeability and exposure to the aminoglycoside antibiotic, hygromycin.

2019-06-08 | GSE83103 | GEO

Disseminated Mycobacterium tilburgii infection in a person with AIDS: A case report.

Project description:BackgroundMycobacterium tilburgii is a nonculturable, nontuberculous mycobacterium that occasionally causes serious infections in individuals with immune deficiencies. Owing to its nonculturable nature, its antimicrobial susceptibility has not been assessed, and the optimal treatment regimen is unclear. Herein, we report a case of disseminated M. tilburgii infection in a person with AIDS, identified using metagenomics next-generation sequencing (mNGS) and polymerase chain reaction (PCR).Case presentationA 33-year-old man presented with a 3-month history of abdominal pain, lymphadenopathy, intermittent night hot flashes, night sweats, and weight loss. No pathogen was detected during initial routine investigations. M. tilburgii was subsequently identified in a left cervical lymph node sample using mNGS. Furthermore, M. tilburgii infection was detected in a bone marrow sample based on PCR of 16S rRNA and hsp65 gene sequencing. The person was treated with a combination of moxifloxacin, clarithromycin, ethambutol, rifabutin, and amikacin. The laboratory results improved, and the patient's symptoms resolved.ConclusionM. tilburgii may be missed in diagnostic tests because it cannot be grown using routine culture techniques. Early diagnosis and timely and effective treatment are critical in patients with M. tilburgii infection; therefore, molecular techniques are recommended for patients with suspected M. tilburgii infection.

| S-EPMC11336850 | biostudies-literature

Genetic Underpinnings of Carotenogenesis and Light-Induced Transcriptome Remodeling in the Opportunistic Pathogen Mycobacterium kansasii.

Project description:Mycobacterium kansasii (Mk) causes opportunistic pulmonary infections with tuberculosis-like features. The bacterium is well known for its photochromogenicity, i.e., the production of carotenoid pigments in response to light. The genetics defining the photochromogenic phenotype of Mk has not been investigated and defined pigmentation mutants to facilitate studies on the role of carotenes in the bacterium's biology are not available thus far. In this study, we set out to identify genetic determinants involved in Mk photochromogenicity. We screened a library of ~150,000 transposon mutants for colonies with pigmentation abnormalities. The screen rendered a collection of ~200 mutants. Each of these mutants could be assigned to one of four distinct phenotypic groups. The insertion sites in the mutant collection clustered in three chromosomal regions. A combination of phenotypic analysis, sequence bioinformatics, and gene expression studies linked these regions to carotene biosynthesis, carotene degradation, and monounsaturated fatty acid biosynthesis. Furthermore, introduction of the identified carotenoid biosynthetic gene cluster into non-pigmented Mycobacterium smegmatis endowed the bacterium with photochromogenicity. The studies also led to identification of MarR-type and TetR/AcrR-type regulators controlling photochromogenicity and carotenoid breakdown, respectively. Lastly, the work presented also provides a first insight into the Mk transcriptome changes in response to light.

| S-EPMC9861118 | biostudies-literature

Molecular model for studying the uncultivated fungal pathogen Lacazia loboi.

Project description:Lacazia loboi is an uncultivated fungal pathogen of humans and dolphins that causes cutaneous and subcutaneous infections only in the tropical areas of the Americas. It was recently found by phylogenetic analysis that this unusual pathogen is closely related to Paracoccidioides brasiliensis and to the other fungal dimorphic members of the order Onygenales. That original phylogenetic study used universal primers to amplify well-known genes. However, this approach cannot be applied to the study of other proteins. We have developed a strategy for studying the gene encoding the gp43 homologous protein of P. brasiliensis in L. loboi. The gp43 protein was selected because it has been found that this P. brasiliensis antigen strongly reacts when it is used to test sera from patients with lacaziosis. The principle behind this idea was to obtain the gp43 amino acid sequence of P. brasiliensis and other homologous fungal sequences from GenBank and design primers from their aligned conserved regions. These sets of primers were used to amplify the selected regions with genomic DNA extracted from the yeast-like cells of L. loboi from experimentally infected mice. Using this approach, we amplified 483 bp of the L. loboi gp43-like gene. These sequences had 85% identity at the nucleotide level and 75% identity with the deduced amino acid sequences of the P. brasiliensis gp43 protein. The identity of the 483-bp DNA fragment was confirmed by phylogenetic analysis. This analysis revealed that the L. loboi gp43-like deduced amino acid sequence formed a strongly supported (100%) sister group with several P. brasiliensis gp43 sequences and that this taxon in turn was linked to the other fungal sequences used in this analysis. This study shows that the use of a molecular model for investigation of the genes encoding important proteins in L. loboi is feasible.

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