Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
ERJ Open Res ; 10(4)2024 Jul.
Article in English | MEDLINE | ID: mdl-38978544

ABSTRACT

Rationale: Nontuberculous mycobacteria (NTM) has been reported to be transmitted between people with cystic fibrosis (CF) attending CF centres. A suspected Mycobacterium abscessus outbreak was investigated at the University of Texas Southwestern (UTSW) Adult CF Program using a combination of pathogen genomic sequencing and epidemiologic methods. The objectives of the present study were to apply the Healthcare-Associated Links in Transmission of NTM (HALT NTM) study to investigate the occurrence of potential healthcare-associated transmission and/or acquisition of NTM among people with CF infected with genetically similar NTM isolates. Methods: Whole-genome sequencing of respiratory M. abscessus isolates from 50 people with CF receiving care at UTSW was performed to identify genetically similar isolates. Epidemiologic investigation, comparison of respiratory and environmental isolates, and home residence watershed mapping were studied. Measurements and main results: Whole-genome sequencing analysis demonstrated seven clusters of genetically similar M. abscessus (four ssp. abscessus and three ssp. massiliense). Epidemiologic investigation revealed potential opportunities for healthcare-associated transmission within three of these clusters. Healthcare environmental sampling did not recover M. abscessus, but did recover four human disease-causing species of NTM. No subjects having clustered infections lived in the same home residence watershed. Some subjects were infected with more than one M. abscessus genotype, both within and outside of the dominant circulating clones. Conclusions: Healthcare-associated person-to-person transmission of M. abscessus appears to be rare at this centre. However, polyclonal infections of M. abscessus species and subspecies, not originating from the endemic hospital environment, suggest multiple shared modes of acquisition outside the healthcare setting.

2.
Ann Am Thorac Soc ; 20(5): 677-686, 2023 05.
Article in English | MEDLINE | ID: mdl-36656594

ABSTRACT

Rationale: Outbreaks of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) have been reported at CF centers with conflicting conclusions. The occurrence of NTM at the UVMC (University of Vermont Medical Center) adult CF program was investigated. Objectives: Use the HALT NTM (Healthcare-associated Links in Transmission of NTM) toolkit to investigate the healthcare-associated transmission and/or acquisition of NTM among pwCF having genetically similar NTM isolates. Methods: Whole genome sequencing of NTM isolates from 23 pwCF was conducted to identify genetically similar NTM isolate clusters (30 or fewer single-nucleotide polymorphism differences). The epidemiological investigation, comparison of respiratory and healthcare environmental isolates, and home residence watershed mapping were analyzed. Results: Whole genome sequencing analysis revealed two clusters of NTM isolates (Mycobacterium avium and M. intracellulare ssp. chimaera) among pwCF. The epidemiologic investigation demonstrated opportunities for healthcare-associated transmission within both clusters. Healthcare environmental M. avium isolates revealed no genetic similarity to respiratory isolates. However, M. intracellulare ssp. chimaera respiratory isolates revealed greater genetic similarity to a hospital water biofilm isolate than to each other. Neither cluster had all subjects residing in the same watershed. Conclusions: This study suggests the healthcare-associated transmission of M. avium among pwCF is unlikely at UVMC but supports the healthcare-associated environmental acquisition of M. intracellulare ssp. chimaera. The presence of genetically similar isolates alone is insufficient to confirm healthcare-associated transmission and/or acquisition. The HALT NTM toolkit standardizes outbreak investigation with genetic analysis, epidemiologic investigation, healthcare environmental sampling, and home of residence watershed identification to test the frequency and nature of healthcare-associated NTM transmission among pwCF.


Subject(s)
Cystic Fibrosis , Mycobacterium Infections, Nontuberculous , Mycobacterium , Pneumonia , Humans , Adult , Mycobacterium avium Complex , Nontuberculous Mycobacteria , Mycobacterium Infections, Nontuberculous/epidemiology , Lung
3.
J Appl Microbiol ; 132(4): 3302-3314, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34919308

ABSTRACT

AIMS: Mycobacterium abscessus subsp. abscessus (MABS) is an emerging, opportunistic pathogen found globally in freshwater biofilms and soil. Typically, isolates are treated as a uniform group of organisms and very little is known about their comparative survival in healthy host cells. We posit that environmentally- and clinically derived isolates, show differential infectivity in immune cells and resistance to innate defenses. METHODS AND RESULTS: Six MABS isolates were tested including three water biofilm/soil and three sputum-derived isolates. A clinical MABS type strain and an environmental isolate of Arthrobacter were also included. MABS counts were significantly higher compared to Arthrobacter after co-culture with Acanthamoeba lenticulata, BEAS-2B epithelial cells, alveolar macrophages and the THP-1 macrophage cell line. A rough sputum-derived MABS isolate emerged as an isolate with higher virulence compared to others tested, as both a pellicle and cord former, survivor in the human cell models tested, inducer of high and prolonged production of pro-inflammatory cytokines, and the capacity to evade LL-37. CONCLUSIONS: Findings support intraspecies variation between MABS isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: These data indicate subversion of host immune defenses by environmental and clinical MABS isolates is nuanced and maybe isolate dependent, providing new information regarding the pathogenesis of NTM infections.


Subject(s)
Mycobacterium Infections, Nontuberculous , Mycobacterium abscessus , Biofilms , Humans , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/genetics , Sputum , Virulence
4.
J Bacteriol ; 203(6)2021 03 15.
Article in English | MEDLINE | ID: mdl-33431432

ABSTRACT

Free-living amoebae are ubiquitous in aquatic environments and act as environmental reservoirs for nontuberculous mycobacteria. Mycobacterium avium subsp. hominissuis recovered from Acanthamoeba has been demonstrated to be more virulent in both human and murine models. Here, we investigate the persistence of M. avium subsp. hominissuis after short-term (2 weeks) and long-term (42 weeks) co-culture in Acanthamoeba lenticulata We hypothesize that A. lenticulata-adapted M. avium subsp. hominissuis demonstrate phenotypic and genomic changes facilitating intracellular persistence in naïve Acanthamoeba and human macrophages. M. avium subsp. hominissuis CFU in co-culture with A. lenticulata were recorded every 2 weeks up to 60 weeks. While A. lenticulata-associated M. avium subsp. hominissuis CFU did not significantly change across 60 weeks of co-culture, longer adaptation time in amoebae reduced colony size. Isolates recovered after 2 or 42 weeks of amoebae co-culture were referred as "early-adapted" and "late-adapted" M. avium subsp. hominissuis, respectively. Whole genome sequencing was performed on amoebae-adapted isolates with pan-genome comparisons to the original M. avium subsp. hominissuis isolate. Next, amoebae-adapted isolates were assessed for their persistence in A. lenticulata, A. castellanii, and human THP-1 macrophages. Multiplex cytokine/chemokine analyses were conducted on THP-1 culture supernatants.  Compared to the original isolate, counts of late-adapted M. avium subsp. hominissuis were reduced in Acanthamoeba and contrary to expectations, lower counts were also observed in THP-1 macrophages with concomitant decrease in TNFa, IL-6, and MIP-1b suggesting that host adaptation may influence the inflammatory properties of M. avium IMPORTANCE Short-term interaction between Acanthamoeba and M. avium has been demonstrated to increase infectivity in human and murine models of infection, establishing the paradigm that amoebae "train" M. avium in the environment by selecting for phenotypes capable of enduring in human cells. We investigate this phenomenon further by determining the consequence of long-term amoebae adaptation on M. avium subsp. hominissuis persistence in host cells. We monitored genomic changes across long-term Acanthamoeba co-culture and report significant changes to the M. avium subsp. hominissuis genome in response to amoebae-adaptation and reduced colony size. Furthermore, we examined isolates co-cultured with A. lenticulata for 2 or 42 weeks and provide biological evidence that long-term co-culture in amoebae reduces M. avium persistence in human macrophages.

SELECTION OF CITATIONS
SEARCH DETAIL
...