Explore the vast range of titles available.

Introduction The incidence of Mycobacterium abscessus complex (MABC) infections is rising, becoming a major pathogen of nontuberculous mycobacteria responsible for pulmonary disease (PD) and extrapulmonary disease (ED). However, studies on the clinical characteristics of MABC-ED remain limited. Methods A 7-year retrospective analysis was conducted on MABC-ED cases at Zhongshan Hospital in Shanghai, China. We analyzed predisposing factors, clinical features, metagenomic sequencing (MS) results, drug susceptibility testing (DST), and genomic characteristics of MABC-ED patients, comparing the data with those of PD cases. Results Among 17 MABC-ED patients, 15 had predisposing risk factors and underlying conditions, with 2 of 3 patients with rheumatic disease showing poor prognosis. The diagnostic performance of metagenomic sequencing for MABC-ED was comparable to that for MABC-PD. However, MABC-ED samples exhibited distinct microbiome features and a more diverse mycobacterial community structure compared to PD. Resistance rates among extrapulmonary MABC isolates were observed as follows: 0% (amikacin), 20% (macrolides), 30% (linezolid), and 40% (cefoxitin). One case showed paradoxical results between erm (41) T28 sequevar and susceptibility phenotype. Genomic analysis revealed no specific dominant circulating clones (DCC) for MABC-ED isolates. Conclusion MABC-ED patients commonly present with risk factors and underlying diseases. Metagenomic sequencing diagnosis of MABC-ED poses challenges, and DST and whole genome sequencing data indicate diversity among MABC-ED isolates. Our study provides detailed data on MABC-ED, contributing to a better understanding of its disease characteristics.

Mycobacterium abscessus , a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus . How and when these clones emerged and spread globally is unclear. Here, we use evolutionary analyses of isolates from individuals both with and without CF to reconstruct the population history, spatiotemporal spread and recent transmission networks of the DCCs. We demonstrate synchronous expansion of six unrelated DCCs in the 1960s, a period associated with major changes in CF care and survival. Each of these clones has spread globally as a result of rare intercontinental transmission events. We show that the DCCs, but not environmentally acquired isolates, exhibit a specific smoking-associated mutational signature and that current transmission networks include individuals both with and without CF. We therefore propose that the DCCs initially emerged in non-CF populations but were then amplified and spread through the CF community. While individuals with CF are probably the most permissive host, non-CF individuals continue to play a key role in transmission networks and may facilitate long-distance transmission. In this Article, the authors perform evolutionary analyses of M. abscessus clinical isolates and report the emergence of dominant circulating clones (DCCs) in non-cystic fibrosis (CF) individuals followed by amplification in the CF community.

Purpose Mycobacterial liquid culturing typically requires six weeks or longer, primarily because of the slow growth rate of Mycobacterium tuberculosis . This study aimed to evaluate the potential of shortening the duration of mycobacterial liquid culturing in healthcare settings with high prevalence rates of non-tuberculous mycobacteria. Methods We retrospectively analyzed the relationship between mycobacterial species and time to positive testing of liquid cultures from sputum samples using the Mycobacteria Growth Indicator Tube system over a 3.5-year period beginning in July 2020 at a university hospital in Japan. Results We analyzed 15,147 sputum culture samples and found a 1.1% positivity rate for Mycobacterium tuberculosis complex, while the rates for Mycobacterium avium complex and Mycobacterium abscessus were 17.6% and 2.1%, respectively. The median time to positivity was 17 days for Mycobacterium tuberculosis complex, 9 days for Mycobacterium avium complex, and 4 days for Mycobacterium abscessus . Comparing a 4-week culture period with an eight-week period, the positivity rates for Mycobacterium avium complex and Mycobacterium abscessus were 97.0% and 99.4%, respectively. Conclusion In settings with a high incidence of non-tuberculous mycobacteria, the basic liquid culturing period can be safely shortened to 4 weeks without significantly compromising detection sensitivity, except for the samples that are highly suspected to contain tuberculosis, extremely slow-growing mycobacteria, smear-positive, or nucleic acid amplification testing positive.

Free-living amoebae are thought to represent an environmental niche in which amoeba-resistant bacteria may evolve towards pathogenicity. To get more insights into factors playing a role for adaptation to intracellular life, we characterized the transcriptomic activities of the emerging pathogen Mycobacterium abscessus in amoeba and murine macrophages (Mϕ) and compared them with the intra-amoebal transcriptome of the closely related, but less pathogenic Mycobacterium chelonae. Data on up-regulated genes in amoeba point to proteins that allow M. abscessus to resist environmental stress and induce defense mechanisms, as well as showing a switch from carbohydrate carbon sources to fatty acid metabolism. For eleven of the most upregulated genes in amoeba and/or Mϕ, we generated individual gene knock-out M. abscessus mutant strains, from which ten were found to be attenuated in amoeba and/or Mϕ in subsequence virulence analyses. Moreover, transfer of two of these genes into the genome of M. chelonae increased the intra-Mϕ survival of the recombinant strain. One knock-out mutant that had the gene encoding Eis N-acetyl transferase protein (MAB_4532c) deleted, was particularly strongly attenuated in Mϕ. Taken together, M. abscessus intra-amoeba and intra-Mϕ transcriptomes revealed the capacity of M. abscessus to adapt to an intracellular lifestyle, with amoeba largely contributing to the enhancement of M. abscessus intra-Mϕ survival.

Background Mycobacterium abscessus (MAB), a rapidly growing non-tuberculous mycobacterium, presents severe therapeutic challenges due to its intrinsic and acquired multidrug resistance. Notably, MAB exhibits phenotypic heterogeneity, with smooth (S) and rough (R) morphotypes displaying distinct drug susceptibility phenotypes. Results We systematically examined the phenotypic diversity and drug susceptibility profiles of 100 clinical MAB isolates, including 79 R-type, 13 S-type, and 8 mixed (M) morphotypes. The three morphotypes (R, S, M) exhibited distinct drug resistance profiles. Both R-type and S-type strains showed broad-spectrum resistance to fluoroquinolones, tetracycline derivatives, and carbapenems. In contrast, S-type strains remained fully susceptible to clofazimine (CFZ), linezolid (LNZ), and trimethoprim-sulfamethoxazole (TMS). Notably, significant differences in resistance to capreomycin (CAP) and clofazimine (CFZ) were observed among the three morphotypes. Genotypic analysis revealed a homogeneous distribution of key resistance genes ( erm (41), rrl , rrs ) across morphotypes. Conclusions Our findings highlight the relationship between MAB morphotypes and antibiotic resistance is complex and drug specific. It is necessary to integrate morphotype with genotypic profiling and phenotypic characterization to better understand the complex resistance landscape of MAB and to guide more effective therapeutic strategy.

Mycobacterium abscessus (MABS) is an emerging pathogen causing severe infections, particularly in cystic fibrosis (CF) patients. A prospective multicentre study included CF patients from four hospitals in Madrid between January 2022 and January 2024. Respiratory samples were collected, and MABS isolates were analysed to determine their antibiotic resistance profiles, growth dynamics, infection kinetics, intracellular behaviour, and pathogenicity. Intracellular bacterial growth and macrophage viability were evaluated through THP-1 cell infection experiments, with and without amikacin. Phenotypic susceptibility testing and genotypic susceptibility testing were also conducted. Among 148 patients, 28 MABS isolates were detected from 16 patients (10.8%), and the first isolate from each patient was analysed. Isolation was more prevalent in younger individuals (median age 24.4 vs. 28.4 years, p = 0.049), and most isolates (81.25%) were identified as M. abscessus subsp. abscessus (MABSa) . MABS isolates exhibited high resistance rates (>85%) to doxycycline, tobramycin, ciprofloxacin, moxifloxacin (75%) and cotrimoxazole (56.3%). Amikacin resistance (18.8%) was higher than expected, and inducible (10/16 isolates) or acquired (1/16 isolate) macrolide resistance was found in 68.8% of strains. Phenotypic and genotypic testing results were fully concordant. Tigecycline demonstrated strong in vitro activity, and resistance to imipenem, linezolid, and cefoxitin remained low. Rough strains displayed lower optical density values in later growth stages, probably due to their increased aggregation. In THP-1 cell infection experiments, rough strains showed higher intracellular bacterial loads with statistically significant differences observed at 2 hours (both with and without amikacin) and at 72 hours (with amikacin) post infection. Notably, rough strains also exhibited a higher internalisation index and greater impact on THP-1 cell viability, especially in the absence of amikacin.

Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense ( M. massiliense ) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. The prevalence of Clone 1 in non-CF patients in the US and the relationship of sporadic US isolates to outbreak clones are not known. We surveyed a reference US Mycobacteria Laboratory and a US biorepository of CF-associated Mycobacteria isolates for Clone 1. We then compared genomic variation and antimicrobial resistance (AMR) mutations between sporadic non-CF, CF, and outbreak Clone 1 isolates. Among reference lab samples, 57/147 (39%) of patients with M. massiliense had Clone 1, including pulmonary and extrapulmonary infections, compared to 11/64 (17%) in the CF isolate biorepository. Core and pan genome analyses revealed that outbreak isolates had similar numbers of single nucleotide polymorphisms (SNPs) and accessory genes as sporadic US Clone 1 isolates. However, pulmonary outbreak isolates were more likely to have AMR mutations compared to sporadic isolates. Clone 1 isolates are present among non-CF and CF patients across the US, but additional studies will be needed to resolve potential routes of transmission and spread.

This study investigates the genetic diversity of Mycobacterium abscessus ( Mab ), a bacteria known for causing difficult-to-treat infections. Researchers performed transposon-sequencing (TnSeq) on 21 different clinical isolates of Mab to identify essential and non-essential genes in each strain. Through this analysis, they identified core genes required for growth across all strains. Interestingly, they also identified genes whose requirement for growth or “essentiality” were subspecies, lineage, and isolate-specific. This study reveals that Mab’ s genetic diversity translates into significant functional differences among clinical isolates. Insights from this paper lay essential groundwork for future studies exploring the biological and clinical implications of genetic diversity in Mab clinical isolates. Understanding this diversity could guide targeted therapies and offer new insights into managing infections caused by Mab , a growing public health concern.

Mycobacterium abscessus ( M. abscessus ) infection is a significant public-health concern due to its resistance to multiple antibiotics and associated treatment challenges. There is a pressing need for a rapid and effective method capable of reliably identifying M. abscessus drug resistance. Our study aimed to investigate the capacity of matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) to identify M. abscessus drug-resistant isolates, offering potential proteomic spectrum markers for detecting resistant strains in clinical diagnosis and treatment. With the aid of machine learning, particularly the decision-tree algorithm, predictive models demonstrated excellent performance with 100% sensitivity and specificity. Peaks at 4,062 Da, 7,518 Da, 8,359 Da and 2,493 Da were potential biomarkers that can distinguish between phenotypes resistant or susceptible to amikacin, linezolid, clarithromycin and cefoxitin, respectively. Besides diagnosing these phenotypes, the combination of machine learning and MALDI-TOF can identify patterns of resistance and susceptibility to various drugs in serially sampled isolates. In an analysis of nine serially collected samples from a single patient, MALDI-TOF could differentiate between M. abscessus strains resistant to three drugs—amikacin, linezolid and clarithromycin—and those completely susceptible to these drugs, based on distinct peak intensities. Furthermore, alterations in the patterns of amikacin and clarithromycin resistance/susceptibility influenced the MALDI-TOF spectra in serial isolates, whereas changes in susceptibility to linezolid did not affect the patterns. Hence, MALDI-TOF could be considered an efficient and dependable method for identifying M. abscessus drug resistance. This diagnostic tool has the potential to streamline the traditionally lengthy process of antimicrobial susceptibility testing while maintaining reliable results.

Smooth and rough colony morphotypes of Mycobacterium abscessus are associated with virulence, but some isolates form both smooth and rough colonies, impeding successful morphotype identification. Reportedly, smooth/rough morphotypes are also related to the glycopeptidolipid (GPL) genotype. However, the accuracy of GPL genotyping to discriminate morphotypes and the relationship between GPL genotype and clinical characteristics of M abscessus lung disease have not been verified. A retrospective analysis of colony morphology, GPL genotype, and clinical data from 182 patients with M abscessus lung disease was conducted. Of 194 clinical isolates, 126 (65.0%), 15 (7.7%), and 53 (27.3%) exhibited rough, smooth, and mixed colony morphotypes, respectively. Glycopeptidolipid genotyping indicated that 86.7% (13 of 15) of smooth isolates belonged to the GPL-wild type (WT) group, whereas 98.4% (124 of 126) of rough isolates belonged to the GPL-mutant type (MUT) group. Therefore, GPL genotyping accurately distinguished between smooth and rough morphotypes. Mixed colony morphotypes were also divided into GPL-WT (18.9%) and GPL-MUT (81.1%) groups. Further analysis revealed that patients infected with the GPL-MUT group presented with significantly worse baseline clinical characteristics and exacerbated episodes of lung disease. Glycopeptidolipid genotyping accurately distinguishes smooth and rough colony morphotypes. Patients infected with the GPL-MUT genotype exhibit worse clinical characteristics and are at a higher risk of exacerbated lung disease.