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BMC Veterinary Research Jan 2021Mycobacterium avium complex (MAC) causes a chronic infectious in the birds known as avian mycobacteriosis. Almost all species of the birds are susceptible to MAC which...
BACKGROUND
Mycobacterium avium complex (MAC) causes a chronic infectious in the birds known as avian mycobacteriosis. Almost all species of the birds are susceptible to MAC which consists of two closely related species of mycobacteria, that is, M. avium and M. intracellulare. This study aimed to determine the occurrence of Mycobacterium avium subsp. avium (MAA) in chickens and captive birds in selected states of Peninsular Malaysia.
RESULTS
A 300 fecal samples were collected from village chickens (n = 100), layer chickens (n = 100) and captive birds (n = 100). Fecal samples were split into two aliquots for microbiological and molecular detection of MAA. Microbiology detection consisted of microscopy (Ziehl-Neelsen staining) and culture of samples decontaminated with 1% Cetylperidinium chloride and vancomycin, nalidixic acid and amphotericin B (VNA) antibiotic cocktail [vancomycin (VAN) 100 μg/ml, nalidixic acid (NAL) 100 μg/ml and amphotericin B (AMB) 50 μg/ml] onto Löwenstein-Jensen (L-J). Molecular detection (PCR-IS901) was performed to detect MAA DNA from the feces and PCR-16S rRNA and IS901 for identification of genus Mycobacterium and Mycobacterium avium sub species avium isolated onto L-J. All samples (296) were AFB negative smear. M. avium was isolated in 0.3% (1/296) samples by culture and detected in 2.5% (6/242) samples by PCR (IS901). Other mycobacteria were found in 1.7% (5/296) chickens. Of five isolates, two were identified as Mycobacterium terrae and M. engbaekii and remaining isolates were not sequenced. Birds positive for M. avium included White Pelican (n = 1) Black Hornbill (n = 1), Macaw (n = 2), Cockatoo (n = 2) and village chicken (n = 1).
CONCLUSION
It is concluded that chickens and birds were infected with M. avium in selected areas of Peninsular Malaysia. Although, PCR is rapid, reliable and cost effective method for detection of M. avium in a subclinical stage, the culture of the avian feces should still be used as a reference test for the diagnosis of avian tuberculosis.
Topics: Animals; Birds; Chickens; DNA, Bacterial; Feces; Malaysia; Mycobacterium; Nontuberculous Mycobacteria; Polymerase Chain Reaction; RNA, Ribosomal, 16S; Tuberculosis, Avian
PubMed: 33413380
DOI: 10.1186/s12917-020-02695-8 -
Journal of Clinical Microbiology Oct 2023Macrolides, such as clarithromycin, are crucial in the treatment of nontuberculous mycobacteria (NTM). NTM are notoriously innately drug resistant, which has made the...
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 and , 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 gene). Chromosomally encoded genes have been identified in many of the macrolide-resistant isolates, but not in . 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 variant, (55) which was found either on the chromosome or on a plasmid in highly macrolide-resistant clinical isolates of . The chromosomal (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 (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 (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.
Topics: Humans; Anti-Bacterial Agents; Mycobacterium chelonae; Macrolides; Drug Resistance, Bacterial; Clarithromycin; Mycobacterium; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Chromosomes
PubMed: 37724858
DOI: 10.1128/jcm.00628-23 -
International Journal of... 2023Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium... (Review)
Review
Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with β-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a β-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without β-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the β-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.
Topics: Humans; beta-Lactamase Inhibitors; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium tuberculosis; Carbapenems; Penicillins; Clavulanic Acid; Microbial Sensitivity Tests; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous
PubMed: 37721224
DOI: 10.4103/ijmy.ijmy_131_23 -
Frontiers in Immunology 2021Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens autophagic machinery. Nontuberculous mycobacteria... (Review)
Review
Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens autophagic machinery. Nontuberculous mycobacteria (NTMs) are ubiquitous microbes, have become increasingly prevalent, and are emerging as clinically important strains due to drug-resistant issues. Compared to (Mtb), the causal pathogen for human tuberculosis, the roles of autophagy remain largely uncharacterized in the context of a variety of NTM infections. Compelling evidence suggests that host autophagy activation plays an essential role in the enhancement of antimicrobial immune responses and controlling pathological inflammation against various NTM infections. As similar to Mtb, it is believed that NTM bacteria evolve multiple strategies to manipulate and hijack host autophagy pathways. Despite this, we are just beginning to understand the molecular mechanisms underlying the crosstalk between pathogen and the host autophagy system in a battle with NTM bacteria. In this review, we will explore the function of autophagy, which is involved in shaping host-pathogen interaction and disease outcomes during NTM infections. These efforts will lead to the development of autophagy-based host-directed therapeutics against NTM infection.
Topics: Animals; Anti-Bacterial Agents; Autophagy; Biological Evolution; Drug Resistance, Bacterial; Host-Pathogen Interactions; Humans; Immunity, Innate; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 34552591
DOI: 10.3389/fimmu.2021.728742 -
Scientific Reports Aug 2019A 59-year-old tobacco smoker male with chronic bronchitis living in Taravao, French Polynesia, Pacific, presented with a two-year growing nodule in the middle lobe of...
A 59-year-old tobacco smoker male with chronic bronchitis living in Taravao, French Polynesia, Pacific, presented with a two-year growing nodule in the middle lobe of the right lung. A guided bronchoalveolar lavage inoculated onto Löwenstein-Jensen medium yielded colonies of a rapidly-growing non-chromogenic mycobacterium designed as isolate P7213. The isolate could not be identified using routine matrix-assisted laser desorption ionization-time of flight-mass spectrometry and phenotypic and probe-hybridization techniques and yielded 100% and 97% sequence similarity with the respective 16S rRNA and rpoB gene sequences of Mycobacterium virginiense in the Mycobacterium terrae complex. Electron microscopy showed a 1.15 µm long and 0.38 µm large bacillus which was in vitro susceptible to rifampicin, rifabutin, ethambutol, isoniazid, doxycycline and kanamycin. Its 4,511,948-bp draft genome exhibited a 67.6% G + C content with 4,153 coding-protein genes and 87 predicted RNA genes. Genome sequence-derived DNA-DNA hybridization, OrthoANI and pangenome analysis confirmed isolate P7213 was representative of a new species in the M. terrae complex. We named this species "Mycobacterium mephinesia".
Topics: Bronchoalveolar Lavage; Genome, Bacterial; Humans; Lung; Male; Middle Aged; Mycobacterium; Nontuberculous Mycobacteria; Polynesia; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 31371776
DOI: 10.1038/s41598-019-47674-8 -
Memorias Do Instituto Oswaldo Cruz 2022Non-tuberculous mycobacteria (NTMs) cause diseases known as mycobacteriosis and are an important cause of morbidity and mortality. The diagnosis of pulmonary disease...
BACKGROUND
Non-tuberculous mycobacteria (NTMs) cause diseases known as mycobacteriosis and are an important cause of morbidity and mortality. The diagnosis of pulmonary disease caused by NTM is hampered by its clinical similarity with tuberculosis (TB) and by the lack of an accurate and rapid laboratory diagnosis.
OBJECTIVES
Detect DNA from NTMs directly from lung samples using real-time polymerase chain reaction (qPCR) for amplification of 16S rRNA. Additionally, DNA sequencing (hsp65 and rpoB genes) was used to identify the species of MNTs.
METHODS
A total of 68 sputum samples (54 with suspected NTMs and 14 with TB) from patients treated at a referral hospital were used.
FINDINGS
Of these, 27/54 (50%) were qPCR positive for NTMs and 14/14 TB patients (controls) were qPCR negative with an almost perfect concordance (Kappa of 0.93) with the Mycobacterium spp. culture. Sequencing confirmed the presence of NTM in all positive samples. The most common species was Mycobacterium gordonae (33%), followed by Mycobacterium abscessus (26%), Mycobacterium fortuitum (22%), Mycobacterium avium (15%) and Mycobacterium peregrinum (4%).
MAIN CONCLUSIONS
The qPCR technique for detecting NTMs targeting 16S rRNA has the potential to detect NTMs and rapidly differentiate from Mycobacterium tuberculosis. However, it is necessary to identify the species to help in the differential diagnosis between disease and contamination, and to guide the choice of the therapeutic scheme.
Topics: Humans; Lung; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; RNA, Ribosomal, 16S; Real-Time Polymerase Chain Reaction; Tuberculosis
PubMed: 35920498
DOI: 10.1590/0074-02760220031 -
American Journal of Respiratory Cell... Aug 2020The incidence and prevalence of nontuberculous mycobacteria (NTM) lung disease is rising worldwide and accounts for most clinical cases of NTM disease. NTM infections... (Review)
Review
The incidence and prevalence of nontuberculous mycobacteria (NTM) lung disease is rising worldwide and accounts for most clinical cases of NTM disease. NTM infections occur in both immunocompetent and immunocompromised hosts. Macrophages are the primary host cells that initiate an immune response to NTM. Defining the molecular events that govern the control of infection within macrophages is fundamental to understanding the pathogenesis of NTM disease. Here, we review key macrophage host signaling pathways that contribute to the host immune response to pulmonary NTM infections. In this review, we focus primarily on NTM that are known to cause lung disease, including , , and .
Topics: Animals; Humans; Lung Diseases; Macrophages; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Signal Transduction
PubMed: 32160017
DOI: 10.1165/rcmb.2019-0241TR -
Antimicrobial Agents and Chemotherapy Feb 2021Infections caused by nontuberculous mycobacteria (NTM) are increasing globally. complex (MAC) and complex are the most frequently encountered NTM, and oral treatment...
Infections caused by nontuberculous mycobacteria (NTM) are increasing globally. complex (MAC) and complex are the most frequently encountered NTM, and oral treatment options are extremely limited for these pathogens, especially for the complex. In this study, the potency of omadacycline, a new tetracycline derivative, was tested against 111 isolates of NTM. MIC testing was performed as recommended by the Clinical and Laboratory Standards Institute against 70 isolates of rapidly growing mycobacteria (RGM), of which >90% were tetracycline resistant. These included subsp. (20 isolates), subsp. (3), (15 isolates), (7 isolates), the group, including six doxycycline-resistant isolates (12 isolates), and the group, including four doxycycline-resistant isolates (10 isolates). Forty-one isolates of slowly growing mycobacteria (SGM), including 16 isolates of MAC, were also tested. Omadacycline was active against all RGM species, with MIC ranges of 0.004 to 0.25 and 0.06 to 1 μg/ml for 80% and 100% inhibition, respectively. For subsp. , MICs were 0.06 and 0.12 μg/ml with 80% and 100% inhibition, respectively. There was considerable trailing of the omadacycline endpoint with the RGM. MICs of tigecycline exhibited no trailing and were generally within 1 to 2 dilutions of the 100% inhibition omadacycline MICs. While there was no trailing observed in SGM, omadacycline MICs were higher (MIC range, 8 to >16 μg/ml; = 41), as previously noted with tigecycline. This study supports further research of omadacycline, including clinical trials, for the treatment of RGM infections, especially .
Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Mycobacteriaceae; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Tetracyclines
PubMed: 33288634
DOI: 10.1128/AAC.01947-20 -
Infection and Immunity Jul 2021Although nontuberculous mycobacteria (NTM) are considered opportunistic infections, incidence and prevalence of NTM infection are increasing worldwide becoming a major... (Review)
Review
Although nontuberculous mycobacteria (NTM) are considered opportunistic infections, incidence and prevalence of NTM infection are increasing worldwide becoming a major public health threat. Innate immunity plays an essential role in mediating the initial host response against these intracellular bacteria. Specifically, macrophages phagocytose and eliminate NTM and act as antigen-presenting cells, which trigger downstream activation of cellular and humoral adaptive immune responses. Identification of macrophage receptors, mycobacterial ligands, phagosome maturation, autophagy/necrosis, and escape mechanisms are important components of this immunity network. The role of the macrophage in mycobacterial disease has mainly been studied in tuberculosis (TB), but limited information exists on its role in NTM. In this review, we focus on NTM immunity, the role of macrophages, and host interaction in NTM infection.
Topics: Adaptive Immunity; Host-Pathogen Interactions; Humans; Immunity, Innate; Macrophages; Microbial Viability; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Phagocytosis
PubMed: 34097459
DOI: 10.1128/IAI.00812-20 -
International Journal of Molecular... Aug 2020Outside of and , nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections... (Review)
Review
Outside of and , nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections caused by NTM show an increased incidence in immunocompromised patients and patients with underlying structural lung disease. The true global prevalence of NTM infections remains unknown because many countries do not require mandatory reporting of the infection. This is coupled with a challenging diagnosis and identification of the species. Current therapies for treatment of NTM infections require multidrug regimens for a minimum of 18 months and are associated with serious adverse reactions, infection relapse, and high reinfection rates, necessitating discovery of novel antimycobacterial agents. Robust drug discovery processes have discovered inhibitors targeting mycobacterial membrane protein large 3 (MmpL3), a protein responsible for translocating mycolic acids from the inner membrane to periplasm in the biosynthesis of the mycobacterial cell membrane. This review focuses on promising new chemical scaffolds that inhibit MmpL3 function and represent interesting and promising putative drug candidates for the treatment of NTM infections. Additionally, agents (FS-1, SMARt-420, C10) that promote reversion of drug resistance are also reviewed.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Biological Transport; Drug Discovery; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Humans; Iodophors; Isoxazoles; Membrane Transport Proteins; Mycobacterium Infections, Nontuberculous; Mycolic Acids; Nontuberculous Mycobacteria; Polysaccharides; Spiro Compounds
PubMed: 32867307
DOI: 10.3390/ijms21176202