Publications by authors named "Adrian Zelazny"

Treatment of pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem).

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Treatment of pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem, meropenem).

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Article Synopsis
  • - The genome of NIH1002, which was isolated in 2011 from a case of widespread disease, has been sequenced using advanced technologies known as PacBio long-read and HiSeq short-read.
  • - This genome consists of 43 contigs, with a significant N50 value of 2.65 Mb, indicating it is highly contiguous.
  • - It contains a total of 13,295 protein-coding genes, making it the most complete genome sequenced so far.
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Background: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation.

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Rationale: The prevalence of nontuberculous mycobacterial (NTM) pulmonary disease varies geographically in the United States. Previous studies indicate that the presence of certain water-quality constituents in source water increases NTM infection risk.

Objective: To identify water-quality constituents that influence the risk of NTM pulmonary infection in persons with cystic fibrosis in the United States.

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Background: Mycobacterium abscessus (MAB) is the mycobacterial species least susceptible to antimicrobials. Infections are difficult to treat, and cure rates are below 50% even after a combination of 4-5 drugs for many months.

Objectives: To examine antimicrobial susceptibilities and treatment recommendations in light of what is known about mechanisms of resistance and pharmacodynamics/pharmacokinetics (PK/PD) interactions.

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Background: subspecies ( ) is increasingly recognized as an emerging bacterial pathogen, particularly in cystic fibrosis (CF) patients and CF centres' respiratory outbreaks. We characterized genomic and phenotypic changes in 15 serial isolates from two CF patients (1S and 2B) with chronic pulmonary M. massiliense infection leading to death, as well as four isolates from a CF centre outbreak in which patient 2B was the index case.

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Article Synopsis
  • Subcutaneous phaeohyphomycosis usually affects healthy individuals after trauma but can become severe in people with CARD9 deficiencies or those who have had transplants due to unclear protective mechanisms.
  • A patient with a severe case of this infection harbored harmful mutations in the CLEC7A gene, leading to impaired immune responses against the fungus Corynespora cassiicola.
  • Research using a mouse model revealed that both Dectin-1 and CARD9 are crucial for producing key immune signals (TNF-α and IL-1β) that help kill this fungus, and a study of additional patients showed that many had similar mutations affecting immune function.
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Mycobacterium abscessus is an emerging nontuberculous mycobacterium (NTM) pathogen infecting susceptible people with cystic fibrosis (CF) and non-CF bronchiectasis. Here, we demonstrated the activity of an FDA-approved drug, disulfiram, against drug-susceptible and drug-resistant M. abscessus strains utilizing and intracellular macrophage assays and a zebrafish embryo infection model.

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To further clarify differences in the risk for nontuberculous mycobacterial pulmonary infection (NTM-PI) among ethnic populations in Hawaii, USA, we conducted a retrospective cohort study among beneficiaries of Kaiser Permanente Hawaii (KPH). We abstracted demographic, socioeconomic, clinical, and microbiological data from KPH electronic health records for 2005-2019. An NTM-PI case-patient was defined as a person from whom >1 NTM pulmonary isolate was obtained.

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Antibiotics are a modifiable iatrogenic risk factor for the most common human nosocomial fungal infection, invasive candidiasis, yet the underlying mechanisms remain elusive. We found that antibiotics enhanced the susceptibility to murine invasive candidiasis due to impaired lymphocyte-dependent IL-17A- and GM-CSF-mediated antifungal immunity within the gut. This led to non-inflammatory bacterial escape and systemic bacterial co-infection, which could be ameliorated by IL-17A or GM-CSF immunotherapy.

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Clarithromycin resistance in Mycobacterium abscessus subsp. , , and occurs through induction of (41) or mutations in (23S rRNA) genes. Phenotypic detection of clarithromycin resistance is hindered by the need for extended incubation as well as co-occurrence of mixed populations of M.

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SARS-CoV-2 variants of concern (VOCs) that increase transmission or disease severity or reduce diagnostic or vaccine efficacy continue to emerge across the world. Current methods available to rapidly detect these can be resource intensive and thus sub-optimal for large-scale deployment needed during a pandemic response. Here, we describe a CRISPR-based assay that detects mutations in spike gene CRISPR PAM motif or seed regions to identify a pan-specific VOC single-nucleotide polymorphism (SNP)) ((D614G) and Alpha- and Delta-specific (S982A and D950N) SNPs.

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The Cryptococcus gattii species complex has often been referred to as a primary pathogen due to its high infection frequency among apparently immunocompetent patients. In order to scrutinize the immune status of patients and the lineages of etiologic agents, we analyzed patient histories and the molecular types of etiologic agents from 135 global C. gattii cases.

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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.

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Mycobacterium  genavense is a challenging opportunistic pathogen to diagnose and manage in patients with human immunodeficiency virus (HIV). Persistent immunosuppression or protracted immune reconstitution inflammatory syndrome can lead to complicated clinical courses. We describe 3 cases of M.

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: We characterized BCG isolates found in lung and brain samples from a previously vaccinated patient with IFNγR1 deficiency. The isolates collected displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susceptibility and virulence traits. : We report a case of a patient with partial recessive IFNγR1 deficiency who developed disseminated BCG infection after neonatal vaccination (BCG-vaccine).

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Distinguishing disseminated Mycobacterium marinum from multifocal cutaneous disease in persons with human immunodeficiency virus/AIDS can present a diagnostic challenge, especially in the context of immune reconstitution inflammatory syndrome (IRIS). In this work, we demonstrate the utility of flow cytometry and whole genome sequencing (WGS) to diagnose disseminated M. marinum unmasked by IRIS following initiation of antiretroviral therapy.

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We evaluated saliva (SAL) specimens for SARS-CoV-2 reverse transcriptase PCR (RT-PCR) testing by comparison of 459 prospectively paired nasopharyngeal (NP) or midturbinate (MT) swabs from 449 individuals with the aim of using saliva for asymptomatic screening. Samples were collected in a drive-through car line for symptomatic individuals ( = 380) and in the emergency department (ED) ( = 69). The percentages of positive and negative agreement of saliva compared to nasopharyngeal swab were 81.

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Introduction: is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a novel NO generator, in a CF patient with pulmonary disease, and examined heterogeneity of response to NO .

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