Whole-Genome Sequencing of Alcaligenes faecalis HZ01, with Potential to Inhibit Nontuberculous Mycobacterial Growth.
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ABSTRACT:
SUBMITTER: Fernandes HMZ
PROVIDER: S-EPMC8483659 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Bacteria within the genus Alcaligenes, exhibit diverse properties but remain largely unexplored at genome scale. To shed light on the genome structure, heterogeneity and traits of Alcaligenes species, the genome of a tannery effluent isolated Alcaligenes faecalis subsp. phenolicus MB207 was sequenced and assembled. The genome was compared to the whole genome sequences of genus Alcaligenes present in the National Centre for Biotechnology Information database. Core, pan and species specific gene sequences i.e. singletons were identified. Members of this genus did not portray exceptional genetic heterogeneity or conservation and out of 5,166 protein coding genes from pooled genome dataset, 2429 (47.01%) contributed to the core, 1193 (23.09%) to singletons and 1544 (29.88%) to accessory genome. Secondary metabolite forming apparatus, antibiotic production and resistance was also profiled. Alcaligenes faecalis subsp. phenolicus MB207 genome consisted of a copious amount of bioremediation genes i.e. metal tolerance and xenobiotic degrading genes. This study marks this strain as a prospective eco-friendly bacterium with numerous benefits for the environment related research. Availability of the whole genome sequence heralds an opportunity for researchers to explore enzymes and apparatus for sustainable environmental clean-up as well as important compounds/substance production.
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Project description:Alcaligenes faecalis subsp. faecalis NCIB 8687, the betaproteobacterium from which arsenite oxidase had its structure solved and the first "arsenate gene island" identified, provided a draft genome of 3.9 Mb in 186 contigs (with the largest 15 comprising 90% of the total) for this opportunistic pathogen species.
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Project description:The factors predisposing toward the development of pulmonary nontuberculous mycobacterial (pNTM) disease and influencing disease progression remain unclear. Impaired immune responses have been reported in individuals with pNTM disease, but data are limited and inconsistent. In this study, we sought to use gene expression profiling to examine the host response to pNTM disease. Microarray analysis of whole-blood gene expression was performed on 25 subjects with pNTM disease and 27 uninfected control subjects with respiratory disease. Gene expression results were compared with phenotypic variables and survival data. Compared with uninfected control subjects, pNTM disease was associated with downregulation of 213 transcripts enriched for terms related to T cell signaling, including IFNG. Reduced IFNG expression was associated with more severe computed tomography changes and impaired lung function. Mortality was associated with the expression of transcripts related to the innate immune response and inflammation, whereas transcripts related to T and B cell function were associated with improved survival. These findings suggest that pNTM disease is associated with an aberrant immune response, which may reflect an underlying propensity to infection or result from NTM infection itself. There were important differences in the immune response associated with survival and mortality in pNTM disease.
| S-EPMC5894497 | biostudies-literature
Project description:Here we present and analyze the complete genome of Alcaligenes faecalis strain Mc250 (Mc250), a bacterium isolated from the roots of Mimosa calodendron, an endemic plant growing in ferruginous rupestrian grasslands in Minas Gerais State, Brazil. The genome has 4,159,911 bp and 3,719 predicted protein-coding genes, in a single chromosome. Comparison of the Mc250 genome with 36 other Alcaligenes faecalis genomes revealed that there is considerable gene content variation among these strains, with the core genome representing only 39% of the protein-coding gene repertoire of Mc250. Mc250 encodes a complete denitrification pathway, a network of pathways associated with phenolic compounds degradation, and genes associated with HCN and siderophores synthesis; we also found a repertoire of genes associated with metal internalization and metabolism, sulfate/sulfonate and cysteine metabolism, oxidative stress and DNA repair. These findings reveal the genomic basis for the adaptation of this bacterium to the harsh environmental conditions from where it was isolated. Gene clusters associated with ectoine, terpene, resorcinol, and emulsan biosynthesis that can confer some competitive advantage were also found. Experimental results showed that Mc250 was able to reduce (~60%) the virulence phenotype of the plant pathogen Xanthomonas citri subsp. citri when co-inoculated in Citrus sinensis, and was able to eradicate 98% of juveniles and stabilize the hatching rate of eggs to 4% in two species of agricultural nematodes. These results reveal biotechnological potential for the Mc250 strain and warrant its further investigation as a biocontrol and plant growth-promoting bacterium.
| S-EPMC7643998 | biostudies-literature
Project description:Osteomyelitis caused by nontuberculous mycobacteria (NTM) can have severe consequences and a poor prognosis. Physicians therefore need to be alert to this condition, especially in immunocompromised patients. Although the pathogenesis of NTM osteomyelitis is still unclear, studies in immunodeficient individuals have revealed close relationships between NTM osteomyelitis and defects associated with the interleukin-12-interferon-?-tumor necrosis factor-? axis, as well as human immunodeficiency virus infection, various immunosuppressive conditions, and diabetes mellitus. Culture and species identification from tissue biopsies or surgical debridement tissue play crucial roles in diagnosing NTM osteomyelitis. Suitable imaging examinations are also important. Adequate surgical debridement and the choice of appropriate, combined antibiotics for long-term anti-mycobacterial chemotherapy, based on in vitro drug susceptibility tests, are the main therapies for these bone infections. Bacillus Calmette-Guerin vaccination might have limited prophylactic value. The use of multiple drugs and long duration of treatment mean that the therapeutic process needs to be monitored closely to detect potential side effects. Adequate duration of anti-mycobacterial chemotherapy together with regular monitoring with blood and imaging tests are key factors determining the recovery outcome in patients with NTM osteomyelitis.
| S-EPMC4714132 | biostudies-literature
Project description:RationalePulmonary nontuberculous mycobacterial disease (PNTM) often affects white postmenopausal women, with a tall and lean body habitus and higher rates of scoliosis, pectus excavatum, mitral valve prolapse, and mutations in the CFTR gene. These clinical features and the familial clustering of the disease suggest an underlying genetic mechanism.ObjectivesTo map the genes associated with PNTM, whole-exome sequencing was conducted in 12 PNTM families and 57 sporadic cases recruited at the National Institutes of Health Clinical Center during 2001-2013.MethodsWe performed a variant-level and a gene-level parametric linkage analysis on nine PNTM families (16 affected and 20 unaffected) as well as a gene-level association analysis on nine PNTM families and 55 sporadic cases.Measurements and main resultsThe genome-wide variant-level linkage analysis using 4,328 independent common variants identified a 20-cM region on chromosome 6q12-6q16 (heterogeneity logarithm of odds score = 3.9), under a recessive disease model with 100% penetrance and a risk allele frequency of 5%. All genes on chromosome 6 were then tested in the gene-level linkage analysis, using the collapsed haplotype pattern method. The TTK protein kinase gene (TTK) on chromosome 6q14.1 was the most significant (heterogeneity logarithm of odds score = 3.38). In addition, the genes MAP2K4, RCOR3, KRT83, IFNLR1, and SLC29A1 were associated with PNTM in our gene-level association analysis.ConclusionsThe TTK gene encodes a protein kinase that is essential for mitotic checkpoints and the DNA damage response. TTK and other genetic loci identified in our study may contribute to the increased susceptibility to NTM infection and its progression to pulmonary disease.
| S-EPMC5754439 | biostudies-literature
Project description:Mixed infection with multiple species of nontuberculous mycobacteria (NTM) is difficult to identify and to treat. Current conventional molecular-based methods for identifying mixed infections are limited due to low specificity. Here, we evaluated the utility of whole-genome sequencing (WGS) analysis to detect and identify mixed NTM infections. Analytical tools used included PubMLST, MetaPhlAn3, Kraken2, Mykrobe-Predictor and analysis of heterozygous SNP frequencies. The ability of each to identify mixed infections of NTM species was compared. Sensitivity was tested using 101 samples (sequence sets) including 100 in-silico simulated mixed samples with various proportions of known NTM species and one sample of known mixed NTM species from a public database. Single-species NTM control samples (155 WGS samples from public databases and 15 samples from simulated reads) were tested for specificity. Kraken2 exhibited 100% sensitivity and 98.23% specificity for detection and identification of mixed NTM species with accurate estimation of relative abundance of each species in the mixture. PubMLST (99% and 96.47%) and MetaPhlAn3 (95.04% and 83.52%) had slightly lower sensitivity and specificity. Mykrobe-Predictor had the lowest sensitivity (57.42%). Analysis of read frequencies supporting single nucleotide polymorphisms (SNPs) could not detect mixed NTM samples. Clinical NTM samples (n = 16), suspected on the basis of a 16S-23S rRNA gene sequence-based line-probe assay (LPA) to contain more than one NTM species, were investigated using WGS-analysis tools. This identified only a small proportion (37.5%, 6/16 samples) of the samples as mixed infections and exhibited only partial agreement with LPA results. LPAs seem to be inadequate for detecting mixed NTM species infection. This study demonstrated that WGS-analysis tools can be used for diagnosis of mixed infections with different species of NTM.
| S-EPMC8308675 | biostudies-literature
Project description:BackgroundAlcaligenes faecalis is usually causes opportunistic infections in humans. Alcaligenes faecalis infection is often difficult to treat due to its increased resistance to several antibiotics. The results from a clinical study of patients with Alcaligenes faecalis infection may help improve patients' clinical care.MethodsWe conducted a retrospective analysis of all patients presenting with Alcaligenes faecalis infection from January 2014 to December 2019. The medical records of all patients were reviewed for demographic information, clinical symptoms and signs, comorbidities, use of intravenous antibiotics within the past three months, bacterial culture, antibiotics sensitivity test, and clinical outcomes.ResultsSixty-one cases of Alcaligenes faecalis infection were seen during the study period, including 25 cases of cystitis, nine cases of diabetic foot infection, eight cases of pneumonia, seven cases of acute pyelonephritis, three cases of bacteremia, and nine cases of infection at specific sites. Thirty-seven patients (60.7%) had a history of receiving intravenous antibiotics within three months of the diagnosis. Fifty-one (83.6%) cases were mixed with other bacterial infections. Extensively drug-resistant infections have been reported since 2018. The best sensitivity rate to Alcaligenes faecalis was 66.7% for three antibiotics (imipenem, meropenem, and ceftazidime) in 2019. Two antibiotics (ciprofloxacin and piperacillin/tazobactam) sensitivity rates to A. faecalis were less than 50%.ConclusionsThe most frequent Alcaligenes faecalis infection sites, in order, are the bloodstream, urinary tract, skin and soft tissue, and middle ear. The susceptibility rate of Alcaligenes faecalis to commonly used antibiotics is decreasing. Extensively drug-resistant Alcaligenes faecalis infections have emerged.
| S-EPMC7659064 | biostudies-literature
Project description:We report the complete genome sequences of 17 rapidly growing nontuberculous mycobacterial (NTM) strains, including 16 Mycobacterium abscessus complex strains and one M. immunogenum strain. These sequences add value to studies of the genetic diversity of rapidly growing NTM strains recovered from human specimens.
| S-EPMC5034138 | biostudies-literature
Project description:The diagnosis of pulmonary non-tuberculous mycobacterial disease (pNTM) is dependent on the isolation of NTM in culture, which is prone to overgrowth and contamination and may not capture the diversity of mycobacteria present, including rare or unidentified species. This study aimed to develop a culture independent method of detecting and identifying mycobacteria from sputum samples using partial sequencing of the hsp65 gene. DNA was extracted from sputum samples from subjects with pNTM and disease controls. Multiplexed partial sequencing of the hsp65 gene was performed using the Illumina MiSeq and custom primers. A reference database of hsp65 sequences was created for taxonomy assignment. Sequencing results were obtained from 42 subjects (31 cases, 11 controls). Mycobacterial sequences were identified in all subjects. In 90.5% of samples more than one species was found (median 5.5). The species isolated in culture was detected by sequencing in 81% of subjects and was the most abundant species in 62%. The sequencing of NTM from clinical samples reveals a far greater diversity than conventional culture and suggests NTM are present as communities rather than a single species. NTM were found to be present even in the absence of isolation in culture or clinical disease.
| S-EPMC6289444 | biostudies-literature