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Journal of Clinical Tuberculosis and... May 2024Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of...
Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 µg/mL to live cultures of , , , , and American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multi-drug resistant, and extensively drug resistant strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays. Both MABs bound to all mycobacterial species and sub-types tested, albeit to varying degrees. Statistically significant differences in MAB binding activity were observed when comparing the highest and lowest MAB concentrations (p < 0.05) for both MABs GG9 and JG7, irrespective of the resistance profile. Binding affinity increased with an increase in MAB concentration, and optimal binding was observed at 25 µg/mL. JG7 showed better binding activity than GG9. Both MABs also bound to five MOTT species, albeit at varied levels. This non-selective binding to different mycobacterial species suggests a potential role for GG9 and JG7 as adjunctive agents in anti-TB chemotherapy with the aim to enhance bacterial killing.
PubMed: 38601919
DOI: 10.1016/j.jctube.2024.100435 -
Journal of Bone and Joint Infection 2024: Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication associated with significant morbidity. While Gram-positive cocci are...
: Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication associated with significant morbidity. While Gram-positive cocci are the predominant causative organisms, PJIs caused by rapidly growing mycobacteria (RGM) have been reported, albeit at a lower frequency. This study aimed to investigate the characteristics and management of PJI caused by RGM. : A retrospective review was conducted using an institutional PJI database to identify patients diagnosed with PJI due to RGM from January 2010 to December 2021. Clinical data, including demographics, symptoms, comorbidity information, laboratory parameters, surgical procedures, medical treatment and outcomes, were collected and analyzed. : A total of eight patients were identified with PJI caused by RGM during the study period. The median age was 66 years old, and most cases occurred in patients with total knee arthroplasty (). The isolated RGM species included (three cases), (three cases), and one case each of and . Surgical debridement was performed in all cases, with six patients undergoing two-stage revision and two patients requiring amputation. Combination antimicrobial therapy was administered based on antimicrobial susceptibility testing, and the median duration of treatment was 7.5 months. Adverse events related to therapy occurred in 75 % of cases. No relapses were observed during the median follow-up period of 39.6 months. : PJI caused by RGM is a rare complication of total joint arthroplasty. Surgical debridement and combination antimicrobial therapy are the mainstays of treatment. Although clinical cure rates are high, amputation may be required in severe cases.
PubMed: 38601002
DOI: 10.5194/jbji-9-99-2024 -
BMC Microbiology Mar 2024Cameroon is a tuberculosis (TB) burden country with a 12% positivity among TB presumptive cases. Of the presumptive cases with a negative TB test, some are infected with...
BACKGROUND
Cameroon is a tuberculosis (TB) burden country with a 12% positivity among TB presumptive cases. Of the presumptive cases with a negative TB test, some are infected with Non-tuberculous Mycobacteria (NTM). However, the diagnosis of NTM infections remains difficult due to the lack of tools in many laboratories, particularly in resource limited laboratories and remote setting. The present study was undertaken to determine NTM profile and associated comorbidities among TB presumptive people.
METHODS
A retrospective study was conducted from December 2018 to December 2019 in the Tuberculosis-National Reference Laboratory (TB-NRL) for Bacteriological analysis of samples and Jamot Hospital of Yaounde (JHY) for clinical evaluation of confirmed NTM patients. We included in this study data of 5267 TB presumptive people previously diagnosed using three consecutive samples and having culture and SD Bioline results with or without Microscopy and reverse hybridization-based Line Probe Assay(LPA) results. The data on co-morbidities or history of people infected with NTM were then collected from the three participants with available clinical data.
RESULTS
We collected data of 5267 presumptive TB people. Among them, 3436 (65.24%), have a positive culture with 3200 (60.75%) isolates belong to Mycobacterium tuberculosis Complex (MBTC) and 236 (4.48%) to NTM. Our results showed that, 123 (52.11%) NTM were isolated from people with negative microscopy and 113 (47.88%) from people with positive microscopy. Among the 236 NTM, 108 (45.8%) isolates were identified using LPA. M. fortuitum was the most represented species (32.41%) followed by M. intracellulare (19.44%). Sputum had the highest proportion of NTM (56%), followed by bronchial aspirations (31%). The extra-pulmonary samples presented lower proportions of isolates compared to pulmonary samples. Some patients affected with NTM presented comorbidities as HIV infection, Pulmonary tuberculosis, Type 2 diabetes, Chronic bronchitis and Alveolar pneumonia.
CONCLUSIONS
Our study showed the presence of NTM strains among presumptive TB people with a predominance of M. fortuitum and M. intracellulare. It is important to implement a surveillance system of NTM in TB burden country and also to develop a point-of-care test for NTM identification in limited-resource settings.
Topics: Humans; Nontuberculous Mycobacteria; HIV Infections; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Diabetes Mellitus, Type 2; Cameroon; Tuberculosis
PubMed: 38532357
DOI: 10.1186/s12866-024-03256-x -
Discovery Medicine Mar 2024This research project delves into the multifaceted dynamics of Mycobacterium tuberculosis (M.tb) endocarditis, a significant yet uncommon manifestation of tuberculosis...
This research project delves into the multifaceted dynamics of Mycobacterium tuberculosis (M.tb) endocarditis, a significant yet uncommon manifestation of tuberculosis (TB). Beginning with an overview of M.tb and the global challenges posed by TB, we navigate through the bacterium's evolution, transmission modes, and the intricate host immune response. The pathology and pathophysiology of M.tb endocarditis are explored, emphasizing its complexities and the host's efforts to contain the pathogen. The study extends to atypical mycobacterial endocarditis, highlighting the emergence of species like M.chimaera, M.fortuitum, and M.chelonae, with a focus on their association with life-threatening mycobacterial endocarditis. Clinical presentations and complications of M.tb endocarditis are detailed, addressing challenges in diagnosis, drug-resistant, co-infections with Human Immunodeficiency Virus (HIV), and potential sepsis. The research underscores the need for a deeper understanding of M.tb endocarditis to enhance prevention, diagnosis, and treatment strategies. Examining the genetic and environmental factors influencing M.tb endocarditis, the study discusses the interplay of immune-related genes, environmental conditions, and predispositions contributing to infection susceptibility. Despite challenges in treatment due to its rarity, the research highlights current protocols, surgical interventions, and promising pharmaceutical developments. Lastly, unraveling these intricate factors is crucial for refining strategies and conducting large-scale trials to address this global health threat effectively.
Topics: Humans; Mycobacterium tuberculosis; Tuberculosis; Endocarditis
PubMed: 38531785
DOI: 10.24976/Discov.Med.202436182.41 -
Journal of Infection and Public Health May 2024The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species...
BACKGROUND
The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited.
METHODS
This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source.
RESULTS
Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively.
CONCLUSIONS
This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.
Topics: Animals; Humans; Male; Female; Adult; Middle Aged; Aged; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Mycobacterium tuberculosis; Mycobacterium leprae; Panama; Tuberculosis; HIV Infections
PubMed: 38518684
DOI: 10.1016/j.jiph.2024.03.004 -
Frontiers in Veterinary Science 2024Non-tuberculous Mycobacteria (NTM) are mainly environmental but can cause opportunistic infections and diseases in humans and animals. Livestock and wild animals can be...
INTRODUCTION
Non-tuberculous Mycobacteria (NTM) are mainly environmental but can cause opportunistic infections and diseases in humans and animals. Livestock and wild animals can be infected with NTM. In Argentina, there are native wild species facing conservation risks, and they are the focus of protection and reintroduction projects designed to preserve biodiversity in various ecoregions. The aim of this study was to report the presence of NTM in samples collected from four endangered native wild species from nine Argentine provinces, as part of their pre-release health assessment.
METHODS
A total of 165 samples from giant anteater, peccary, tapir and pampas deer were obtained, these included either bronchoalveolar or endotracheal lavages, or oropharyngeal, nasopharyngeal or tracheal swabs. Bacteriological culture followed by molecular identification and sequencing were performed.
RESULTS
A total of 27 NTM were detected, including subsp. , and . Results revealed a 16,36% NTM recovery rate, with the giant anteater showing the highest prevalence among the mammals under study.
DISCUSSION
In Argentina, due to extensive production systems, the interaction between domestic and wild species sharing the same environment is frequent, increasing the exposure of all the species to these NTM. In this way, the transmission of infectious agents from one to another is feasible. Moreover, NTMs might interfere with the diagnosis of bovine tuberculosis and paratuberculosis. These findings emphasize the importance of active health surveillance in conservation programs. It highlights the need to address NTM epidemiology in wildlife and its impact on conservation and public health.
PubMed: 38420209
DOI: 10.3389/fvets.2024.1346514 -
Microbiology Resource Announcements Apr 2024, a fast-growing nontuberculous mycobacterium, is a significant pathogen in healthcare-associated infections, encompassing skin, soft tissue, and pulmonary diseases. In...
, a fast-growing nontuberculous mycobacterium, is a significant pathogen in healthcare-associated infections, encompassing skin, soft tissue, and pulmonary diseases. In this study, we present draft genome sequences from 12 . strains isolated from sputum samples from patients diagnosed with pulmonary infections in Mexico.
PubMed: 38411073
DOI: 10.1128/mra.01022-23 -
BioRxiv : the Preprint Server For... Feb 2024Endolysins are highly evolved bacteriophage-encoded lytic enzymes produced to damage the bacterial cell wall for phage progeny release. They offer promising potential as...
Endolysins are highly evolved bacteriophage-encoded lytic enzymes produced to damage the bacterial cell wall for phage progeny release. They offer promising potential as highly specific lytic proteins with a low chance of bacterial resistance. The diversity in lysin sequences and domain organization can be staggering. analysis of bacteriophage and prophage genomes can help identify endolysins exhibiting unique features and high antibacterial activity, hence feeding the pipeline of narrow-spectrum protein antibiotics. Mycobacteriophage lysis cassettes mostly have two lytic enzymes, LysinA and LysinB. The enzyme LysinA targets peptidoglycan in the cell wall and possesses a modular architecture. LysinB typically contains a single domain and acts upon the mycolyl ester linkages in mycolyl-arabinogalactan-peptidoglycan (Payne et al., 2010). This study aimed to find novel LysinBs against . After a detailed characterization of lysis cassettes from three prophages, we chose to work on a LysinB (hereafter described as LysinB_MF) found in an incomplete prophage (phiE1336, 9.4 kb in strain E1336). LysinB_MF showed low sequence similarity with any other endolysins in the database and formed a separate clade on phylogenetic analysis. LysinB_MF's structure, extracted from the AlphaFold Protein Structure Database, demonstrated a modular architecture with two structurally distinct domains: a peptidoglycan-binding domain (PGBD) at the N-terminal and the characteristic alpha/beta hydrolase domain connected via a linker peptide. We found the alpha/beta hydrolase domain, which is the enzyme-active domain (EAD), contains the conserved Ser-Asp-His catalytic triad with a tunnel-like topology and forms intermolecular hydrogen bonds. The PGBD shows structural similarity to the cell-wall binding domain of an amidase from , hinting at its acquisition due to domain mobility. Our electrostatic potential analysis suggested that PGBD might be essential to the enzyme activity. This was experimentally validated by generating a truncated version of the enzyme, which demonstrated about six-fold decreased activity compared to its native form. The antimycobacterial activity of this enzyme was also compromised in its absence. Based on our analysis, PGBD emerged as an integral constituent of enzymes with diverse functional properties and is predicted to be a conserved cross-kingdom. Overall, this study highlights the importance of mining mycobacterial prophages as a novel endolysin source. It also provides unique insights into the diverse architecture of mycobacteriophage-encoded endolysins and the importance of functional domains for their catalytic activities.
PubMed: 38405724
DOI: 10.1101/2024.02.15.580446 -
Journal of Proteome Research Mar 2024Nontuberculous mycobacteria are opportunistic bacteria pulmonary and extra-pulmonary infections in humans that closely resemble . Although genome sequencing strategies...
Discovery of Species-Specific Proteotypic Peptides To Establish a Spectral Library Platform for Identification of Nontuberculosis Mycobacteria from Mass Spectrometry-Based Proteomics.
Nontuberculous mycobacteria are opportunistic bacteria pulmonary and extra-pulmonary infections in humans that closely resemble . Although genome sequencing strategies helped determine NTMs, a common assay for the detection of coinfection by multiple NTMs with in the primary attempt of diagnosis is still elusive. Such a lack of efficiency leads to delayed therapy, an inappropriate choice of drugs, drug resistance, disease complications, morbidity, and mortality. Although a high-resolution LC-MS/MS-based multiprotein panel assay can be developed due to its specificity and sensitivity, it needs a library of species-specific peptides as a platform. Toward this, we performed an analysis of proteomes of 9 NTM species with more than 20 million peptide spectrum matches gathered from 26 proteome data sets. Our metaproteomic analyses determined 48,172 species-specific proteotypic peptides across 9 NTMs. Notably, (26,008), (12,442), (6487), (1623), subsp. (844), subsp. (580), and (112) displayed >100 species-specific proteotypic peptides. Finally, these peptides and corresponding spectra have been compiled into a spectral library, FASTA, and JSON formats for future reference and validation in clinical cohorts by the biomedical community for further translation.
Topics: Animals; Humans; Proteomics; Chromatography, Liquid; Tandem Mass Spectrometry; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Peptides
PubMed: 38358903
DOI: 10.1021/acs.jproteome.3c00850 -
Southern African Journal of Infectious... 2024Non-tuberculous mycobacteria (NTM) management comprises prolonged therapy that includes macrolides. Non-tuberculous mycobacteria can cause disease in patients with...
BACKGROUND
Non-tuberculous mycobacteria (NTM) management comprises prolonged therapy that includes macrolides. Non-tuberculous mycobacteria can cause disease in patients with predisposing conditions such as HIV and structural lung disease. Local data on NTM disease and macrolide resistance are scarce, and routine antimicrobial susceptibility testing is currently not performed for NTM in South Africa.
OBJECTIVES
This study aims to characterise NTM isolated at Tshepong National Health Laboratory Service (NHLS) according to species and antimicrobial susceptibility pattern.
METHOD
A retrospective data analysis of NTM isolates from Tshepong NHLS was performed from January to June 2020. GenoType NTM-DR was performed on selected isolates where the assay can confirm the species and determine resistance to macrolides and aminoglycosides.
RESULTS
Of the 194 collected NTM isolates, 183 were included in the study. Patients' ages ranged from 1 day to 81 years (median 36 years). The most common specimen was sputum (84.7%), followed by gastric aspirate (6.6%). The most common NTM isolated were (67.6%), (12.6%), (4.3%), (3.9%), and (3.9%). Macrolide resistance occurred in 2.8% of tested isolates; no aminoglycoside resistance was detected. Although most isolates were from males (62.3%), resistance was observed only in females.
CONCLUSION
predominated, with only two and two isolates showing macrolide resistance; aminoglycoside resistance was absent.
CONTRIBUTION
This study highlights the need for increased awareness of NTM, regular nationwide NTM surveillance, and monitoring of resistance trends to guide future patient management and ensure good treatment outcomes.
PubMed: 38322299
DOI: 10.4102/sajid.v39i1.525