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Microbial Drug Resistance (Larchmont,... Aug 2021In this study, we conducted an experimental study to evaluate susceptibility of Q203 against , as well as the major pathogenic nontuberculous mycobacterial species. A...
In this study, we conducted an experimental study to evaluate susceptibility of Q203 against , as well as the major pathogenic nontuberculous mycobacterial species. A total of 344 nonduplicate mycobacterium isolates were randomly selected for susceptibility testing. Overall, Q203 exhibited excellent activity against multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) isolates, whereas it showed high minimum inhibitory concentration (MIC) values for all nontuberculous mycobacteria (NTM) isolates tested. The MIC and MIC values were both 0.008 mg/L for MDR- and XDR-TB isolates, respectively. In contrast, the MIC and MIC values of four NTM species were all >16 mg/L. QcrB of , a component of the CytBC1 complex of the respiratory chain targeted by Q230, shared 89.7% amino acid sequence identity with QcrB, 87.9% with that of , and 84.0% with that of , whereas with low sequence identity observed in QcrB sequence of . Notably, the QcrBs of and contained a 10-amino acid insertion in the linker between the eighth and ninth helical region. In conclusion, our data demonstrate the bipolar distribution of Q203 MICs across mycobacterial species. Compared with the high MICs in four clinically relevant mycobacterial species, MDR- and XDR-TB isolates have extremely low MICs, indicating that Q203 is a particularly promising candidate for TB treatment. In addition, the 10-amino acid insertion within QcrBs of and may be a plausible explanation for the natural resistance to Q203 among these two species.
Topics: Dose-Response Relationship, Drug; Imidazoles; Microbial Sensitivity Tests; Mycobacterium; Piperidines; Pyridines; Tuberculosis, Multidrug-Resistant
PubMed: 33646044
DOI: 10.1089/mdr.2020.0239 -
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 -
Pulmonology 2024Nontuberculous mycobacteria (NTM) are opportunistic human pathogens found in the environment. The transmission seems to be associated with inhalation of aerosol...
INTRODUCTION AND OBJECTIVES
Nontuberculous mycobacteria (NTM) are opportunistic human pathogens found in the environment. The transmission seems to be associated with inhalation of aerosol droplets, ingestion or trauma events. Recent studies indicate that NTM disease is increasing worldwide, however, the true clinical impact of NTM infections is difficult to determine due to challenges in discriminating between disease and colonization as they are ubiquitous in the environment. In addition, understanding the epidemiology of NTM is difficult and has not yet been established. In this work, we used a country NTM representative collection from the National Reference Laboratory for Tuberculosis (NRL-TB) of the National Institute of Health (INSA), to characterize the circulation trends of NTM species in Portugal and the most affected regions, contributing to a better understanding of the NTM epidemiology.
MATERIAL AND METHODS
We conducted a nationwide retrospective study where all individuals with positive NTM cultures at the NRL-TB of the INSA from 2014 to December 2020 were included. Positive cultures were identified using GenoType Mycobacterium CM/AS® (Hain Lifescience) according to manufacturer's instructions, or hsp65 DNA sequencing as previously described. Social-demographic data from patients were also analyzed and patients classified into 3 groups according only to microbiological data, "definite NTM disease", "NTM colonization" and, "possible NTM disease".
RESULTS
In the period 2014-2020, the NRL-TB performed 50397 cultures. Among these, 1118 cultures were NTM positive retrieved from 944. Most of our cases were in patients whose mean age was 64±15.9 years, and no significant differences between gender was observed, although more frequent in male patients. Overall, from the 944 cases, we were able to identified 93 "definite NTM disease" cases and 79 "possible NTM disease". Mycobacterium avium complex (MAC) (40,8%), Mycobacterium abscessus-chelonae complex (MABC) (9,6%) and Mycobacterium fortuitum (6,3%) were responsible for most of the infections. The geographical distribution of NTM cases varied significantly and was possible to observe that was independent of population density. The region were most cases occurred was Lisbon Metropolitan Area (31,9%), followed by North (25,3%) and Centre (24,4%), however North region has the highest number of "definite NTM disease" cases (n=33).
CONCLUSIONS
This is the first national wide epidemiological study on this subject, contributing to a better understanding of NTM dynamics in Portugal. MAC was the NTM species responsible for the majority of infections and, LMA the region with the highest number of cases. It was also possible to conclude that the number of NTM isolates is independent of the demography of the region.
Topics: Humans; Portugal; Mycobacterium Infections, Nontuberculous; Male; Female; Middle Aged; Nontuberculous Mycobacteria; Aged; Retrospective Studies; Adult; Aged, 80 and over; Adolescent; Young Adult
PubMed: 35219623
DOI: 10.1016/j.pulmoe.2022.01.011 -
The Journal of Clinical and Aesthetic... Apr 2021is a rapidly growing mycobacterium known to spread through many sources, including tap water. This organism can have variable presentation between patients which can...
is a rapidly growing mycobacterium known to spread through many sources, including tap water. This organism can have variable presentation between patients which can lead to a delay in diagnosis. Here, we report a series of eight cases of tattoo-associated infections that presented between December 2010 and January 2011, which were later linked to a single tattoo provider using gray tattoo ink made by diluting black ink with nonsterile tap water. In this case series, we emphasize the lack of pathognomonic features of these infections, the variability in culture and biopsy results, the importance of obtaining a culture in addition to a biopsy, and the importance of identifying the source of infection when determining management.
PubMed: 34055187
DOI: No ID Found -
Journal of Wildlife Diseases Apr 2024Mycobacteria of the Mycobacterium tuberculosis complex (MTC) are capable of infecting a wide variety of animals. Wild boar (Sus scrofa) has been recognized as an...
Mycobacteria of the Mycobacterium tuberculosis complex (MTC) are capable of infecting a wide variety of animals. Wild boar (Sus scrofa) has been recognized as an important wildlife reservoir for bovine tuberculosis. We screened wild boar in Slovenia for the presence of (1) Mycobacterium bovis in tissues and (2) antibodies to M. bovis in blood samples. In 2016 and 2017, 1284 tissue samples from 676 wild boar were subjected to cultivation. In 2018 and 2019, blood samples from 132 wild boar were examined using an ELISA kit. None of the MTC species were isolated from the tissue samples, and no antibodies to M. bovis were detected in the blood samples. Several nontuberculous mycobacteria (NTM), identified by 16S rRNA sequencing and/or matrix-assisted laser desorption ionization time-of-flight mass spectrometry, were found in the tissues of 9.8% of the wild boar: Mycobacterium nonchromogenicum, Mycobacterium peregrinum/Mycobacterium septicum, Mycobacterium avium, Mycobacterium engbaekii, Mycobacterium arupense, Mycobacterium algericum, Mycobacterium bohemicum, Mycobacterium confluentis, Mycobacterium flavescens, Mycobacterium fortuitum, Mycobacterium thermoresistibile, and Mycobacterium vaccae. Species-level identification was not possible for 21.2% of the isolates. At the time of the study, wild boar in Slovenia were not at risk from bTB; the significance of the presence of NTM in wild boar remains to be clarified and evaluated from a One Health perspective.
Topics: Animals; Cattle; Swine; Tuberculosis, Bovine; Slovenia; RNA, Ribosomal, 16S; Mycobacterium bovis; Nontuberculous Mycobacteria; Sus scrofa; Cattle Diseases; Swine Diseases
PubMed: 38304986
DOI: 10.7589/JWD-D-23-00123 -
Frontiers in Immunology 2021The mechanisms underlying -induced mycobacteriosis remain unexplored. Using head kidney macrophages (HKM) from catfish (), we report that Ca surge across...
The mechanisms underlying -induced mycobacteriosis remain unexplored. Using head kidney macrophages (HKM) from catfish (), we report that Ca surge across mitochondrial-Ca uniporter (MICU), and consequent mitochondrial ROS (mtROS) production, is imperative for mycobactericidal activity. Inhibition of mtROS alleviated HKM apoptosis and enhanced bacterial survival. Based on RNA interference (RNAi) and inhibitor studies, we demonstrate that the Toll-like receptor (TLR)-2-endoplasmic reticulum (ER) stress-store-operated calcium entry (SOCE) axis is instrumental for activating the mt-Ca/mtROS cascade in -infected HKM. Additionally, pharmacological inhibition of mtROS attenuated the expression of , , and , which suggests a positive feedback loop between ER-stress-induced SOCE and mtROS production. Elevated tumor necrosis factor alpha (TNF-α) levels and caspase-8 activity were observed in HKM consequent to infection, and our results implicate that mtROS is crucial in activating the TNF-mediated caspase-8 activation. Our results for the first time demonstrate mitochondria as an innate immune signaling center regulating mycobacteriosis in fish. We conclude that induced persistent SOCE signaling leads to mtROS production, which in turn activates the TNF-α/caspase-8 axis culminating in HKM apoptosis and bacterial clearance.
Topics: Animals; Calcium; Catfishes; Head Kidney; Macrophages; Mitochondria; Mycobacterium Infections, Nontuberculous; Mycobacterium fortuitum; Reactive Oxygen Species; Signal Transduction; Toll-Like Receptor 2
PubMed: 34987503
DOI: 10.3389/fimmu.2021.748758 -
International Journal of... 2019Mycobacterium fortuitum is ubiquitous in nature and can cause a wide variety of lesions in humans with immunocompromised or antecedent chronic illness. Clinical...
Mycobacterium fortuitum is ubiquitous in nature and can cause a wide variety of lesions in humans with immunocompromised or antecedent chronic illness. Clinical diagnosis is difficult and relapses are seen. This is due to the fact that they are not critically investigated and are not responded to traditional antitubercular treatment and other antibiotics. Herewith, we report a case of M. fortuitum causing laparotomy port infection-causing repeated multiple abscess on the anterior abdominal wall and treated with amikacin and clarithromycin. The wound healed completely and the patient recovered after administering a combination of amikacin and clarithromycin. We conclude that strict standard operating procedures should be followed to prevent mycobacteria other than tuberculosis (MOTT) infections during and after surgical procedures. Any postoperative, chronic infection which is not responding to conventional antibiotics should be highly suspected for such MOTT infections. Antibiotic susceptibility testing should be performed so as to identify the required antibiotic combination and treated accordingly to prevent further complications and to reduce the cost of treatment.
Topics: Abdomen; Adult; Antitubercular Agents; Appendicitis; Disease Management; Humans; Laparotomy; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium fortuitum; Surgical Wound Infection
PubMed: 31793513
DOI: 10.4103/ijmy.ijmy_93_19 -
BMC Infectious Diseases Mar 2021Nontuberculous mycobacteria (NTM) are environmental bacterium that may cause and/or compound respiratory diseases in humans. There are over a hundred NTM species with...
BACKGROUND
Nontuberculous mycobacteria (NTM) are environmental bacterium that may cause and/or compound respiratory diseases in humans. There are over a hundred NTM species with varying pathogenicity's Therefore, it is necessary to characterize the populations at risk for each species.
METHODS
Demographic (age, sex, and state of residence) and microbiological data from 2014 were extracted from Mississippi, Missouri, and Ohio disease surveillance systems. NTM species with > 50 reports were included in the analysis. Patient sex, age, and incidence rates were generated for each of the following NTM species: M. abscessus, M. avium complex (MAC), M. chelonae, M. fortuitum, M. gordonae, M. kansasii, M. mucogenicum, and M. peregrinum.
RESULTS
Analysis by sex showed that M. chelonae,M. fortuitum, M. gordonae,and M. kansasii had significantly higher rates in males than females. Age was not associated with patient rates for several specific NTM species e.g., M. chelonae. Mississippi had the highest patient' rates for M. avium, M. gordonae, M. kansasii, and M. chelonae. Ohio had the highest patient' rates for M. abscessus, M. mucogenicum, and M. peregrinum. The highest patient's rate for M. fortuitum was observed in Missouri.
CONCLUSION
This study showed that NTM infection occurred more frequently in males. The highest rates were observed in Mississippi for most of the NTMs studied. Age was not a strong risk factor for some of the NTM species.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Child, Preschool; Databases, Factual; Female; Humans; Infant; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Prevalence; Risk Factors; Sex Factors; United States; Young Adult
PubMed: 33706712
DOI: 10.1186/s12879-021-05925-y -
Applied Microbiology and Biotechnology Dec 2023Androst-4-ene-3,17-dione (AD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) are important drug intermediates that can be biosynthesized from phytosterols. However,...
Androst-4-ene-3,17-dione (AD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) are important drug intermediates that can be biosynthesized from phytosterols. However, the C9 hydroxylation of steroids via 3-ketosteroid 9α-hydroxylase (KSH) limits AD and 4-HBC accumulation. Five active KshAs, the oxidation component of KSH, were identified in Mycobacterium fortuitum ATCC 35855 for the first time. The deletion of kshAs indicated that the five KshA genes were jointly responsible for C9 hydroxylation during phytosterol biotransformation. MFKDΔkshA, the five KshAs deficient strain, blocked C9 hydroxylation and produced 5.37 g/L AD and 0.55 g/L 4-HBC. The dual function reductase Opccr knockout and 17β-hydroxysteroid dehydrogenase Hsd4A enhancement reduced 4-HBC content from 8.75 to 1.72% and increased AD content from 84.13 to 91.34%, with 8.24 g/L AD being accumulated from 15 g/L phytosterol. In contrast, hsd4A and thioesterase fadA5 knockout resulted in the accumulation of 5.36 g/L 4-HBC from 10 g/L phytosterol. We constructed efficient AD (MFKDΔkshAΔopccr_hsd4A) and 4-HBC (MFKDΔkshAΔhsd4AΔfadA5) producers and provided insights for further metabolic engineering of the M. fortuitum ATCC 35855 strain for steroid productions. KEY POINTS: • Five active KshAs were first identified in M. fortuitum ATCC 35855. • Deactivation of all five KshAs blocks the steroid C9 hydroxylation reaction. • AD or 4-HBC production was improved by Hsd4A, FadA5, and Opccr modification.
Topics: Phytosterols; Mycobacterium fortuitum; Mycobacterium; Mixed Function Oxygenases; Steroids; Biotransformation
PubMed: 37831185
DOI: 10.1007/s00253-023-12812-w -
Journal of Clinical Tuberculosis and... May 2021Rapidly growing mycobacteria (RGM) are found in non-sterile water and often associated with severe post-surgical infections and affect immunocompromised patients. In...
Rapidly growing mycobacteria (RGM) are found in non-sterile water and often associated with severe post-surgical infections and affect immunocompromised patients. In addition, RGM can prevent the host's immune response and have the ability to adhere to and form biofilms on biological and synthetic substrates, making pharmacological treatment difficult because conventional antimicrobials are ineffective against biofilms. Thus, there is an urgent need for new antimicrobial compounds that can overcome these problems. In this context, sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against various microorganisms. Considering the importance of combating RGM-associated infections, this study aimed to evaluate the activity of sulfonamide metal complexes against RGM biofilm. The sulfonamides were tested individually for their ability to inhibit mycobacterial formation and destroy the preformed biofilm of standard RGM strains, such as , , and . All sulfonamides complexed with metals could reduce, at subinhibitory concentrations, the adhesion and biofilm formation of three RGM species in polystyrene tubes. It is plausible that the anti-biofilm capacity of the compounds is due to the inhibition of c-di-GMP synthesis, which is an important signal for RGM biofilm formation. Hence, the impacts and scientific contribution of this study are based on the discovery of a potential new therapeutic option against RGM-associated biofilm infections. Sulfonamides complexed with metals have proven to be a useful and promising tool to reduce microbial adhesion on inert surfaces, stimulating the improvement of methodologies to insert compounds as new antibacterial and coating agents for medical and hospital materials.
PubMed: 33869806
DOI: 10.1016/j.jctube.2021.100217