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MSphere Feb 2024Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did...
UNLABELLED
Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did not prolong QT interval in animal model studies. This study evaluated the antibacterial activity of this novel compound against , , and and . The minimum inhibitory concentration (MIC) of WX-081 against three kinds of non-tuberculous mycobacteria (NTM) clinical strains was determined using microplate-based alamarBlue assay (MABA), and the antibacterial activity of WX-081 against NTM in J774A.1 cells and mice was evaluated. MIC ranges of WX-081 against clinical strains of and were 0.05-0.94 μg/mL, 0.88-7.22 μg/mL ( subsp. ), and 0.22-8.67 μg/mL ( subsp. ), respectively, which were slightly higher than those of BDQ. For , , and , WX-081 can reduce the intracellular bacterial load by 0.13-1.18, 0.18-1.50, and 0.17-1.03 log colony forming units (CFU)/mL, respectively, in a concentration-dependent manner. WX-081 has bactericidal activity against three NTM species in mice. WX-081 exhibited anti-NTM activity to the same extent as BDQ both and . WX-081 is a promising clinical candidate and should be studied further in clinical trials.
IMPORTANCE
Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of , , and during 2000-2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against , , and , in macrophages and mice, respectively.
Topics: Animals; Mice; Mycobacterium abscessus; Mycobacterium avium; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Tuberculosis; Pyridines
PubMed: 38240581
DOI: 10.1128/msphere.00518-23 -
Current Microbiology Jan 2024Nontuberculous mycobacteria (NTM) are environmentally acquired opportunistic pathogens that cause chronic lung disease in susceptible individuals. While presumed to be...
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.
Topics: Humans; Mycobacterium chelonae; Colorado; Ice; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Sequence Analysis; Genomics
PubMed: 38238596
DOI: 10.1007/s00284-023-03589-2 -
Epidemiology of Nontuberculous Mycobacteria in Tuberculosis suspects, Southwest of China, 2017-2022.Frontiers in Cellular and Infection... 2023This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the...
OBJECTIVES
This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the Public Health Clinical Center of Chengdu, China, from January 2017 to December 2022.
METHODS
We retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of strain isolation over 6 years.
RESULTS
The number of samples tested for (MTB) and/or NTM increased each year, while MTB detection decreased and NTM detection rose significantly each year (P=0.03). The average age of NTM patients was 51 ± 17.53 years, with a 14.1% HIV infection rate. The predominant isolates were (MAC) and /, with 96.4% of cases being of Han ethnicity. Amikacin, moxifloxacin, and clarithromycin were effective against and ; linezolid, amikacin, and cefoxitin were effective against /. Over 90% of NTM cases originated from the respiratory tract.
CONCLUSION
The NTM isolation rate in Southwest China has risen in recent years, primarily among elderly patients with a high HIV co-infection rate. The main NTM isolates were MAC and /. Amikacin, moxifloxacin, clarithromycin, and linezolid exhibited strong antibacterial activity against SGM, while amikacin and linezolid displayed relatively better antibacterial activity against RGM. The prevalence of NTM infection may be positively associated with regional economic development and health conditions.
Topics: Humans; Aged; Adult; Middle Aged; Nontuberculous Mycobacteria; Clarithromycin; Amikacin; Linezolid; HIV Infections; Moxifloxacin; Retrospective Studies; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous; Tuberculosis; China; Microbial Sensitivity Tests
PubMed: 38029240
DOI: 10.3389/fcimb.2023.1282902 -
Indian Journal of Medical Microbiology 2023Mycobacterium chelonae typically affect skin and soft tissue. Pleural involvement by this organism is exceedingly rare. A young female presented with persistent...
Mycobacterium chelonae typically affect skin and soft tissue. Pleural involvement by this organism is exceedingly rare. A young female presented with persistent respiratory complaints along with constitutional symptoms. She had already been treated with standard anti-tubercular therapy with inadequate response and had a recent onset of worsening of her symptoms. A detailed evaluation revealed M. chelonae and she responded well to antimicrobials. We report a case of Mycobacterium chelonae lung disease in an immunocompetent patient and its successful management. High index of suspicion with a correct etiological diagnosis is the need of the hour in current era of drug resistance.
Topics: Female; Humans; Lung Diseases; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Adolescent
PubMed: 37945126
DOI: 10.1016/j.ijmmb.2023.100434 -
Infection Control and Hospital... Mar 2024
Topics: Humans; Mycobacterium chelonae; Pneumonia, Ventilator-Associated; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents
PubMed: 37920122
DOI: 10.1017/ice.2023.119 -
The Science of the Total Environment Jan 2024Nontuberculous mycobacteria (NTM) represent an emerging health concern due to their escalating infections worldwide. Although drinking water distribution systems (DWDSs)...
Nontuberculous mycobacteria (NTM) represent an emerging health concern due to their escalating infections worldwide. Although drinking water distribution systems (DWDSs) have been considered as NTM reservoirs and a potential infection route, NTM community at the species level remain largely elusive in DWDSs. This study employed high-throughput sequencing coupled with qPCR to profile NTM community and estimate their abundances at the species level in water and biofilm samples in four DWDSs using three different disinfectants (i.e. free chlorine, chloramine and chlorine dioxide). Results demonstrated the dominance of Mycobacterium paragordonae and Mycobacterium mucogenicum in both biofilm and water across four DWDSs, whereas Mycobacterium abscessus and Mycobacterium chelonae, the two clinically significant species, exhibited low abundance but high prevalence. Comparable NTM community was observed in biofilm across these four DWDSs. Distinct separation of NTM community between SH-chloramine DWDSs water and other DWDSs highlighted the selective pressure of chloramine on NTM community. Furthermore, the research revealed that biofilm and water exhibited distinct NTM community structures, with biofilm harboring more diverse NTM community. Certain NTM species displayed a preference for biofilm, such as Mycobacterium gordonae, while others, like Mycobacterium mucogenicum, were more abundant in water samples (P < 0.05). In terms of NTM community assembly, stochastic processes dominated biofilm, while comparable role of stochastic and deterministic processes was observed in water. In conclusion, this study offers a pioneering and comprehensive insight into the dynamics and assembly mechanisms of NTM community within four DWDSs treated with three distinct disinfectants. These findings serve as a critical foundation for assessing NTM exposure risks and devising effective management strategies within DWDSs.
Topics: Nontuberculous Mycobacteria; Drinking Water; Disinfectants; Chloramines
PubMed: 37907107
DOI: 10.1016/j.scitotenv.2023.168176 -
Frontiers in Microbiology 2023Despite the great diversity of malonate semialdehyde decarboxylases (MSADs), one of five subgroups of the tautomerase superfamily (TSF) found throughout the biosphere,...
Phylogenetic distribution of malonate semialdehyde decarboxylase (MSAD) genes among strains within the genus : evidence of MSAD gene loss in the evolution of pathogenic mycobacteria.
Despite the great diversity of malonate semialdehyde decarboxylases (MSADs), one of five subgroups of the tautomerase superfamily (TSF) found throughout the biosphere, their distribution among strains within the genus remains unknown. In this study, we sought to investigate the phylogenetic distribution of MSAD genes of mycobacterial species via genome analysis of 192 different reference species or subspecies retrieved from NCBI databases. We found that in a total of 87 of 192 strains (45.3%), MSAD-1 and MSAD-2 were distributed in an exclusive manner among species except for 12 strains, including members, with both in their genome. Of note, strains better adapted to the host and of high virulence potential, such as the complex, , , , and subsp. , had no orthologs of MSAD in their genome, suggesting MSAD loss during species differentiation in pathogenic slow-growing . To investigate the MSAD distribution among strains of subspecies, the genome sequences of a total of 255 reference strains from the four subspecies of (43 of subspecies , 162 of subspecies , 49 of subspecies , and 1 of subspecies ) were further analyzed. We found that only 121 of 255 strains (47.4%) had MSADs in their genome, with none of the 49 subsp. strains having MSAD genes. Even in 13 of 121 strains with the MSAD-1 gene in their genome, deletion mutations in the 98th codon causing premature termination of MSAD were found, further highlighting the occurrence of MSAD pseudogenization during species or subspecies differentiation of In conclusion, our data indicated that there are two distinct types of MSADs, MSAD-1 and MSAD-2, among strains in the genus, but more than half of the strains, including pathogenic mycobacteria, and , have no orthologs in their genome, suggesting MSAD loss during host adaptation of pathogenic mycobacteria. In the future, the role of two distinct MSADs, MSAD-1 and MSAD-2, in mycobacterial pathogenesis or evolution should be investigated.
PubMed: 37901833
DOI: 10.3389/fmicb.2023.1275616 -
Emerging Microbes & Infections Dec 2023Numbers of non-tuberculous mycobacteria (NTM) pulmonary diseases (PD) have been repeatedly reported as increasing over the last decades, particularly in Europe. Sound...
Numbers of non-tuberculous mycobacteria (NTM) pulmonary diseases (PD) have been repeatedly reported as increasing over the last decades, particularly in Europe. Sound epidemiological data are however missing for most European regions. This study calculated prevalence and incidence of NTM recovered from patients' lungs in Germany, the largest Central European country, over a five-year period. It furthermore determined regional particularities of NTM species and results from susceptibility testing. 22 German NTM laboratories provided their mycobacteriological diagnostic data of 11,430 NTM isolates recovered from 5998 pulmonary patients representing 30% of all notified NTM-PD cases of Germany from 2016 to 2020. NTM incidence and prevalence were calculated for every study year. The presented epidemiological indicators are particularly reliant as TB surveillance data were used as a reference and TB notification reaches almost 100% in Germany. Laboratory incidence and prevalence of NTM recovered from respiratory samples ranged from 4.5-4.9 and from 5.3-5.8/100,000 for the population of Germany, respectively, and did not change over the five-year study period. Prevalence and incidence were stable also when stratifying for facultative pathogenic NTM, complex (MAIC), and complex (MABSC). The proportion of NTM with drug susceptibility testing (DST) increased from 27.3% (2016) to 43.8% (2020). The unchanging laboratory NTM prevalence/incidence in Germany represents a "ceiling" of possible NTM-PD notification when diagnostic strategies do not change in the coming years. A notable increase in NTM-DST may indicate better notification of NTM-PD and/or awareness of new clinical guidelines but still remains below clinical needs.
Topics: Humans; Nontuberculous Mycobacteria; Prevalence; Incidence; Laboratories; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Lung Diseases
PubMed: 37883336
DOI: 10.1080/22221751.2023.2276342 -
IDCases 2023Mycobacterium franklinii (Mfra) is a recently identified member of the Mycobacterium chelonae-abscessus complex (MCAC), a rapidly growing, acid-fast bacilli that have...
Infective intracardiac lesion in the setting of Mycobacterium franklinii bacteremia identified by cell-free DNA sequencing in a child with acute lymphoblastic leukemia: A potential new foe in intracardiac infections.
Mycobacterium franklinii (Mfra) is a recently identified member of the Mycobacterium chelonae-abscessus complex (MCAC), a rapidly growing, acid-fast bacilli that have the potential to cause invasive human infections. Identification of Mfra is crucial for selecting the appropriate antimicrobial therapy, as Mfra displays a unique susceptibility profile compared to other MCAC members. The literature on Mfra is limited, with a few studies focusing on respiratory and skin infections. To our knowledge, we describe the first reported case of cardiac involvement associated with Mfra bacteremia in a patient with acute lymphoblastic leukemia. The isolation of Mfra through a next-generation sequencing test allowed for prompt identification and subsequent implementation of tailored antimicrobial agents, ultimately resulting in positive clinical outcomes. This case also emphasizes the significance of next-generation testing in managing immunocompromised patients with persistent fever.
PubMed: 37860149
DOI: 10.1016/j.idcr.2023.e01905 -
Photodiagnosis and Photodynamic Therapy Feb 2024Mycobacterium chelonae is a non-tuberculous mycobacteria, which can cause skin infectious granuloma through cosmetic injection. This disease's treatment requires a...
Mycobacterium chelonae is a non-tuberculous mycobacteria, which can cause skin infectious granuloma through cosmetic injection. This disease's treatment requires a combination of sensitive antibiotics and a lengthy treatment cycle. Photodynamic therapy is still effective for patients who are unwilling to take antibiotics orally. In this case, we successfully used fire needle combined with photodynamic therapy to treat skin infectious granulomatosis caused by Mycobacterium chelonei, and achieved satisfactory results. We used fire needle to pretreat cysts and nodules, which improved the diffusion and absorption of locally applied photosensitizers and enhanced the efficacy of photodynamic therapy. However, additional clinical research is necessary to determine the efficacy and safety of fire needle combined with photodynamic therapy for cutaneous infectious granulomatosis.
Topics: Humans; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Photochemotherapy; Photosensitizing Agents; Anti-Bacterial Agents
PubMed: 37813272
DOI: 10.1016/j.pdpdt.2023.103836