-
Microorganisms Jul 2022Nontuberculous mycobacteria (NTM) represent an important group of environmentally saprophytic and potentially pathogenic bacteria that can cause serious mycobacterioses...
Nontuberculous mycobacteria (NTM) represent an important group of environmentally saprophytic and potentially pathogenic bacteria that can cause serious mycobacterioses in humans and animals. The sources of infections often remain undetected except for soil- or water-borne, water-washed, water-based, or water-related infections caused by groups of the complex; and other NTM species, including infection, known as fish tank granuloma, and infection, which is described as a Buruli ulcer. NTM could be considered as water-borne, air-borne, and soil-borne pathogens (sapronoses). A lot of clinically relevant NTM species could be considered due to the enormity of published data on permanent, periodic, transient, and incidental sapronoses. Interest is currently increasing in mycobacterioses diagnosed in humans and husbandry animals (esp. pigs) caused by NTM species present in peat bogs, potting soil, garden peat, bat and bird guano, and other matrices used as garden fertilizers. NTM are present in dust particles and in water aerosols, which represent certain factors during aerogenous infection in immunosuppressed host organisms during hospitalization, speleotherapy, and leisure activities. For this Special Issue, a collection of articles providing a current view of the research on NTM-including the clinical relevance, therapy, prevention of mycobacterioses, epidemiology, and ecology-are addressed.
PubMed: 35893574
DOI: 10.3390/microorganisms10081516 -
Journal of the Association of Medical... Mar 2022is a rapidly growing mycobacterium, ubiquitous in soil and water, but it is an uncommon cause of infections in immunocompetent hosts. Cardiac device infections and...
BACKGROUND
is a rapidly growing mycobacterium, ubiquitous in soil and water, but it is an uncommon cause of infections in immunocompetent hosts. Cardiac device infections and bloodstream infections due to non-tuberculous mycobacteria are rare.
CASE PRESENTATION
We present the case of an 85-year-old patient with infective endocarditis and pacemaker lead infection secondary to .
PubMed: 36340848
DOI: 10.3138/jammi-2021-0003 -
Antimicrobial Agents and Chemotherapy Apr 2023Mycobacterium fortuitum represents one of the most clinically relevant rapid-growing mycobacterial species. Treatments are complex due to antibiotic resistance and to...
Mycobacterium fortuitum represents one of the most clinically relevant rapid-growing mycobacterial species. Treatments are complex due to antibiotic resistance and to severe side effects of effective drugs, prolonged time of treatment, and co-infection with other pathogens. Herein, we explored the activity of NITD-916, a direct inhibitor of the enoyl-ACP reductase InhA of the type II fatty acid synthase in Mycobacterium tuberculosis. We found that this compound displayed very low MIC values against a panel of M. fortuitum clinical strains and exerted potent antimicrobial activity against M. fortuitum in macrophages. Remarkably, the compound was also highly efficacious in a zebrafish model of infection. Short duration treatments were sufficient to significantly protect the infected larvae from M. fortuitum-induced killing, which correlated with reduced bacterial burdens and abscesses. Biochemical analyses demonstrated an inhibition of synthesis of mycolic acids. Resolving the crystal structure of the InhA in complex with NAD and NITD-916 confirmed that NITD-916 is a direct inhibitor of InhA. Importantly, single nucleotide polymorphism leading to a G96S substitution in InhA conferred high resistance levels to NITD-916, thus resolving its target in M. fortuitum. Overall, these findings indicate that NITD-916 is highly active against M. fortuitum both and and should be considered in future preclinical evaluations for the treatment of M. fortuitum pulmonary diseases.
Topics: Animals; Mycobacterium fortuitum; Zebrafish; Mycobacterium tuberculosis; Mycolic Acids; Oxidoreductases
PubMed: 36920188
DOI: 10.1128/aac.01607-22 -
Microbial Drug Resistance (Larchmont,... Jul 2023There is a scarcity of data regarding the antimicrobial susceptibility testing profiles of nontuberculous mycobacterial (NTM) in Israel and other Middle Eastern...
There is a scarcity of data regarding the antimicrobial susceptibility testing profiles of nontuberculous mycobacterial (NTM) in Israel and other Middle Eastern countries. We aimed to describe the antimicrobial susceptibility profiles of NTM in Israel. A total of 410 clinical isolates of NTM, identified to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry or gene sequencing, were included. Minimum inhibitory concentrations for slowly growing mycobacteria (SGM) and rapidly growing mycobacteria (RGM) for 12 and 11 drugs were determined using the Sensititre SLOMYCOI and RAPMYCOI broth microdilution plates, respectively. complex (MAC) was the most frequently isolated species ( = 148; 36%), followed by ( = 93; 23%), group ( = 62; 15%), ( = 27; 7%), and ( = 22; 5%) accounting together for 86% of isolates. The most active agents against SGM were amikacin (98%/85%/100%) and clarithromycin (97%/99%/100%), followed by moxifloxacin (25%/10%/100%) and linezolid (3%/6%/100%) for MAC, , and , respectively. For RGM, the most active agents were amikacin (98%/100%/88%) followed by linezolid (48%/80%/100%) and clarithromycin (39%/28%/94%) for group, , and , respectively. These findings can assist in guiding the treatment of NTM infections.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Linezolid; Anti-Bacterial Agents; Amikacin; Clarithromycin; Israel; Microbial Sensitivity Tests
PubMed: 37219996
DOI: 10.1089/mdr.2023.0024 -
Journal of Basic Microbiology Dec 2022The fatty acid biosynthesis pathway is crucial for the formation of the mycobacterial cell envelope. The fatty acid synthase type-II (FAS-II) components are attractive...
The fatty acid biosynthesis pathway is crucial for the formation of the mycobacterial cell envelope. The fatty acid synthase type-II (FAS-II) components are attractive targets for designing anti-biofilm inhibitors. Literature review, bioinformatics analysis, cloning, and sequencing led to the identification of a novel Mycobacterium fortuitum FAS-II gene MFfabG4 which interacts with mycobacterial proteins involved in biofilm formation. A manually curated M. fortuitum fatty acid biosynthesis pathway has been proposed exploiting functional studies from the Kyoto Encyclopedia of Genes and Genomes and Mycobrowser databases for MFFabG4. M. fortuitum MFfabG4 knockdown strain (FA) was constructed and validated by quantitative polymerase chain reaction. The FA strain displayed unstructured smooth colony architecture, correlating with decreased pathogenicity and virulence. MFfabG4 knockdown resulted in diminished pellicle and attenuated biofilm formation, along with impaired sliding motility, and reduced cell sedimentation. The FA strain showed lowered cell surface hydrophobicity, indicating attenuation in M. fortuitum intracellular infection-causing ability. Stress survival studies showed the requirement of MFfabG4 for survival in a nutrient-starved environment. The results indicate that MFfabG4 maintains the physiology of the cell envelope and is required for the formation of M. fortuitum pellicle and biofilm. The study corroborates the role of MFfabG4 as a pellicle- and biofilm-specific drug target and a potential diagnostic marker for M. fortuitum and related pathogenic mycobacteria.
Topics: Mycobacterium fortuitum; Biofilms; Virulence; Fatty Acids
PubMed: 35736669
DOI: 10.1002/jobm.202200230 -
Frontiers in Cellular and Infection... 2023Mycobacteriophages are viruses that infect members of genus . Because of the rise in antibiotic resistance in mycobacterial diseases such as tuberculosis,...
Mycobacteriophages are viruses that infect members of genus . Because of the rise in antibiotic resistance in mycobacterial diseases such as tuberculosis, mycobacteriophages have received renewed attention as alternative therapeutic agents. Mycobacteriophages are highly diverse, and, on the basis of their genome sequences, they are grouped into 30 clusters and 10 singletons. In this article, we have described the isolation and characterization of a novel mycobacteriophage Kashi-VT1 (KVT1) infecting mc 155 () and isolated from Varanasi, India. KVT1 is a cluster K1 temperate phage that belongs to family as visualized in transmission electron microscopy. The phage genome is 61,010 base pairs with 66.5% Guanine/Cytosine (GC) content, encoding 101 putative open reading frames. The KVT1 genome encodes an immunity repressor, a tyrosine integrase, and an excise protein, which are the characteristics of temperate phages. It also contains genes encoding holin, lysin A, and lysin B involved in host cell lysis. The one-step growth curve demonstrated that KVT1 has a latency time of 90 min and an average burst size of 101 phage particles per infected cell. It can withstand a temperature of up to 45°C and has a maximum viability between pH 8 and 9. Some mycobacteriophages from cluster K are known to infect the pathogenic (); hence, KVT1 holds potential for the phage therapy against tuberculosis, and it can also be engineered to convert into an exclusively lytic phage.
Topics: Humans; Mycobacteriophages; Genome, Viral; Mycobacterium tuberculosis; Mycobacterium smegmatis; Tuberculosis; Bacteriophages
PubMed: 37545854
DOI: 10.3389/fcimb.2023.1173894 -
Microorganisms Sep 2020The constitute a family of varied Gram-positive organisms that include a large number of pathogenic bacteria. Among these, non-tuberculous mycobacteria are endemic... (Review)
Review
The constitute a family of varied Gram-positive organisms that include a large number of pathogenic bacteria. Among these, non-tuberculous mycobacteria are endemic worldwide and have been associated with infections in a large number of organisms, including humans and other mammals and reptiles, as well as fish. In this review, we summarize the most recent findings regarding this group of pathogens in fish. There, four species are most commonly associated with disease outbreaks: the most common of these fish mycobacterial pathogens, , , and . These bacteria have a broad host range: they are zoonotic, and infections have been reported in a large number of fish species. The main route of entry of the bacterium into the fish is through the gastrointestinal route, and the disease is associated with ulcerative dermatitis as well as organomegaly and the development of granulomatous lesions in the internal organs. are slow-growing and fastidious and isolation is difficult and time consuming and diagnostic is mostly performed using serological and molecular tools. Control of the disease is also difficult: there is currently no effective vaccine and infections react poorly to antibiotherapy. For this reason, more research is needed on the subject of these vexing pathogens.
PubMed: 32906655
DOI: 10.3390/microorganisms8091368 -
Frontiers in Cellular and Infection... 2023We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) and .
OBJECTIVES
We aimed to evaluate the activity of PBTZ169 and pretomanid against non-tuberculous mycobacteriosis (NTM) and .
METHODS
The minimum inhibitory concentrations (MICs) of 11 antibiotics, against slow-growing mycobacteria (SGMs) and rapid-growing mycobacteria (RGMs) were tested using the microplate alamarBlue assay. The activities of bedaquiline, clofazimine, moxifloxacin, rifabutin, PBTZ169 and pretomanid against four common NTMs were assessed in murine models.
RESULTS
PBTZ169 and pretomanid had MICs of >32 μg/mL against most NTM reference and clinical strains. However, PBTZ169 was bactericidal against (3.33 and 1.49 log10 CFU reductions in the lungs and spleen, respectively) and (2.29 and 2.24 CFU reductions in the lungs and spleen, respectively) in mice, and bacteriostatic against Mycobacterium avium and . Pretomanid dramatically decreased the CFU counts of (3.12 and 2.30 log10 CFU reductions in the lungs and spleen, respectively), whereas it showed moderate inhibition of and . Bedaquiline, clofazimine, and moxifloxacin showed good activities against four NTMs and . Rifabutin did not inhibit and in mice.
CONCLUSION
PBTZ169 appears to be a candidate for treating four common NTM infections. Pretomanid was more active against , and than against .
Topics: Animals; Mice; Mycobacterium abscessus; Mycobacterium avium; Mycobacterium fortuitum; Mycobacterium chelonae; Clofazimine; Moxifloxacin; Mice, Inbred BALB C; Anti-Bacterial Agents; Nontuberculous Mycobacteria; Mycobacterium Infections; Rifabutin; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests
PubMed: 37077530
DOI: 10.3389/fcimb.2023.1115530 -
Orthopaedic Surgery Jun 2023Periprosthetic joint infection (PJI) caused by non-tubercular mycobacteria (NTM) is uncommon but catastrophic. However, conclusive clinical data on PJI caused by NTM are... (Review)
Review
OBJECTIVE
Periprosthetic joint infection (PJI) caused by non-tubercular mycobacteria (NTM) is uncommon but catastrophic. However, conclusive clinical data on PJI caused by NTM are lacking. In this case series and systematic review, the clinical manifestations, diagnosis, and management of NTM PJI are summarized and analyzed.
METHODS
From 2012 to 2020, we retrospectively analyzed consecutive PJI cases caused by NTM in our institution. A literature review was also conducted from January 2000 to December 2021, utilizing the PubMed, MEDLINE, Cochrane Library, and EMBASE databases to identify all reported NTM-induced PJI cases. The clinical characteristics, demographics, pathogen identification, treatment protocols, and prognosis of NTM PJI were summarized and analyzed.
RESULTS
In this retrospective analysis, seven patients infected with NTM following total joint arthroplasty at our institution were included, including six cases of PJI caused by NTM and one case of septic arthritis (SA) caused by NTM. There were six men and one woman, and their average age was 62.3 years. The average interval between TJA and PJI onset was 4 months. The preoperative serological markers, including the mean ESR (51 mm/h), CRP (4.0 mg/dL), fibrinogen (5.7 g/L), and D-dimer (1.1 g/L), were increased. Six patients underwent staged revision surgery, and one patient with SA received antibiotic-loaded bone cement beads to treat the infection. After an average of 33 months of observation following surgical intervention, none of the patients showed any symptoms of infection recurrence. From 2000 to 2021, 68 patients with NTM PJI were found in 39 studies in the published literature. Reinfections occurred within 1 year after arthroplasty in more than half (53.2%) of the patients. M. fortuitum and M. abscesses were the most prevalent rapidly growing mycobacteria (RGM) in all PJI patients, whereas Mycobacterium avium intracellulare (MAC) was the most prevalent slowly growing mycobacterium (SGM). The corresponding antibiotics were amikacin and ethambutol. The rate of culture-negative without specific clinical symptoms was as high as 36.4% (12/33), while 45% (18/40) utilized additional diagnostic techniques such as NGS. A final clinical follow-up record was available for 59 patients (86.7%; mean follow-up period, 29 months), and 10.1% of patients failed to respond to treatment.
CONCLUSION
Orthopaedic surgeons should consider NTM in patients with negative routine cultures who are at risk for Mycobacterium infection. Treatment options rely on the accurate result of microbiologic identification and drug sensitivity testing, and to achieve this, it may be necessary to send multiple culture specimens, extend the culture time, and change the culture medium. Every effort should be made to identify NTM and its various subtypes through modern diagnostic tools if necessary.
Topics: Male; Female; Humans; Middle Aged; Arthroplasty, Replacement, Knee; Retrospective Studies; Arthroplasty, Replacement, Hip; Mycobacterium; Arthritis, Infectious; Prosthesis-Related Infections
PubMed: 37154097
DOI: 10.1111/os.13661 -
Annali Dell'Istituto Superiore Di Sanita 2023Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to...
INTRODUCTION
Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to their intrinsic drug-resistance. In Italy, no major nationwide study on NTM epidemiology and drug susceptibility was performed.
METHODS
Data on the epidemiology of 7,469 NTM clinical isolates identified in Italy in 2016-2020 and on the minimum inhibitory concentrations (MICs) of 1,506 of these strains were analysed.
RESULTS
Overall, 63 species were identified in 42 hospital laboratories located in 16 out of 20 regions, with Mycobacterium avium complex (MAC) being the most frequently isolated, followed by M. gordonae, M. xenopi, M. abscessus. The MICs of 12 drugs for MAC, M. xenopi, M. kansasii, M. abscessus, M. fortuitum and M. chelonae were interpreted for clinical significance (susceptible, intermediate, resistant) based on the guidelines published by the Clinical and Laboratory Standards Institute in November 2018.
CONCLUSIONS
Our data are in line with other nationwide studies and may be of value for further update of microbiological and clinical guidelines.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests; Italy
PubMed: 37337988
DOI: 10.4415/ANN_23_02_06