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Microorganisms Jul 2023Skin and soft tissue infections caused by non-tuberculous mycobacteria are occurring more frequently in recent years. However, chronic skin and soft tissue lesions... (Review)
Review
Skin and soft tissue infections caused by non-tuberculous mycobacteria are occurring more frequently in recent years. However, chronic skin and soft tissue lesions present a challenge for clinicians, as the diagnostic work-up and definitive diagnosis require knowledge and available laboratory resources. We present here the case of a 66-year-old male patient who presented with painful abscess-like nodules on his right hand and forearm, which worsened after treatment with an anti-TNF-a agent. The fluid specimen taken from the lesion was positive for mycobacteria according to the acid-fast stain. was identified, first by next-generation sequencing and finally grown on culture, after eight weeks. Acknowledging the complexity of diagnosing and managing infections by non-tuberculous mycobacteria, and especially , we provide a review of the current epidemiology, clinical characteristics, diagnosis and management of infection.
PubMed: 37512971
DOI: 10.3390/microorganisms11071799 -
MBio Oct 2023Tuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen. , the causative agent, has perfected many ways to replicate...
Tuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen. , the causative agent, has perfected many ways to replicate and persist within its host. While mycobacteria induce vacuole damage to evade the toxic environment and eventually escape into the cytosol, the host recruits repair machineries to restore the MCV membrane. However, how lipids are delivered for membrane repair is poorly understood. Using advanced fluorescence imaging and volumetric correlative approaches, we demonstrate that this involves the recruitment of the endoplasmic reticulum (ER)-Golgi lipid transfer protein OSBP8 in the / system. Strikingly, depletion of OSBP8 affects lysosomal function accelerating mycobacterial growth. This indicates that an ER-dependent repair pathway constitutes a host defense mechanism against intracellular pathogens such as .
Topics: Humans; Vacuoles; Dictyostelium; Endoplasmic Reticulum; Mycobacterium marinum; Mycobacterium tuberculosis; Tuberculosis
PubMed: 37676004
DOI: 10.1128/mbio.00943-23 -
MSystems Jun 2023The antibiotic-tolerant biofilms present in tuberculous granulomas add an additional layer of complexity when treating mycobacterial infections, including tuberculosis...
The antibiotic-tolerant biofilms present in tuberculous granulomas add an additional layer of complexity when treating mycobacterial infections, including tuberculosis (TB). For a more efficient treatment of TB, the biofilm forms of mycobacteria warrant specific attention. Here, we used (Mmr) as a biofilm-forming model to identify the abundant proteins covering the biofilm surface. We used biotinylation/streptavidin-based proteomics on the proteins exposed at the Mmr biofilm matrices to identify 448 proteins and proteomics to detect 91 Mmr proteins from the mycobacterial granulomas isolated from adult zebrafish. and proteomics data are available via ProteomeXchange with identifiers PXD033425 and PXD039416, respectively. Data comparisons pinpointed the molecular chaperone GroEL2 as the most abundant Mmr protein within the and proteomes, while its paralog, GroEL1, with a known role in biofilm formation, was detected with slightly lower intensity values. To validate the surface exposure of these targets, we created in-house synthetic nanobodies (sybodies) against the two chaperones and identified sybodies that bind the mycobacterial biofilms and those present in granulomas. Taken together, the present study reports a proof-of-concept showing that surface proteomics and proteomics combined is a valuable strategy to identify surface-exposed proteins on the mycobacterial biofilm. Biofilm surface-binding nanobodies could be eventually used as homing agents to deliver biofilm-targeting treatments to the sites of persistent biofilm infection. IMPORTANCE With the currently available antibiotics, the treatment of TB takes months. The slow response to treatment is caused by antibiotic tolerance, which is especially common among bacteria that form biofilms. Such biofilms are composed of bacterial cells surrounded by the extracellular matrix. Both the matrix and the dormant lifestyle of the bacterial cells are thought to hinder the efficacy of antibiotics. To be able to develop faster-acting treatments against TB, the biofilm forms of mycobacteria deserve specific attention. In this work, we characterize the protein composition of Mmr biofilms in bacterial cultures and in mycobacteria extracted from infected adult zebrafish. We identify abundant surface-exposed targets and develop the first sybodies that bind to mycobacterial biofilms. As nanobodies can be linked to other therapeutic compounds, in the future, they can provide means to target therapies to biofilms.
Topics: Animals; Proteomics; Mycobacterium marinum; Zebrafish; Single-Domain Antibodies; Anti-Bacterial Agents; Tuberculosis; Biofilms
PubMed: 37184670
DOI: 10.1128/msystems.01073-22 -
Cureus Jul 2023is a ubiquitous and opportunist agent that may cause infections related to water activities in humans. It causes mainly skin and soft tissue infections, and other...
is a ubiquitous and opportunist agent that may cause infections related to water activities in humans. It causes mainly skin and soft tissue infections, and other forms of presentation are uncommon. A 27-year-old man presented to the Emergency Department of a tertiary hospital due to a cervical foreign-body sensation that evolved into right cervical swelling and consumption symptoms. He was a waiter on a cruise in the Douro river. Weeks after the initial presentation, the diagnosis of infection was made by positive nucleic acid amplification tests (NAAT) in tissues obtained by excisional biopsy of cervical adenopathy. Treatment with rifampicin and clarithromycin was started. The symptoms improved, and there was a decrease in the adenopathy number and size. Although adenitis as initial presentation of the disease is rare, the identification of the agent by NAAT and favorable response to treatment supported the diagnosis.
PubMed: 37575752
DOI: 10.7759/cureus.41833 -
Pathogens (Basel, Switzerland) Jun 2023Prior to the COVID-19 pandemic, tuberculosis (TB) was the leading cause of death globally attributable to a single infectious agent, ranking higher than HIV/AIDS....
Prior to the COVID-19 pandemic, tuberculosis (TB) was the leading cause of death globally attributable to a single infectious agent, ranking higher than HIV/AIDS. Consequently, TB remains an urgent public health crisis worldwide. Oridonin (7a,20-Epoxy-1a,6b,7,14-tetrahydroxy-Kaur-16-en-15-one Isodonol, CHO, Ori), derived from the plant, is a natural compound that exhibits antioxidant, anti-inflammatory, and antibacterial properties. Our objective was to investigate whether Ori's antioxidant and antibacterial effects could be effective against the infection ()-infected cells and zebrafish. We observed that Ori treatment significantly impeded infection in lung epithelial cells, while also suppressing inflammatory response and oxidative stress in -infected macrophages. Further investigation revealed that Ori supplementation inhibited the proliferation of in zebrafish, as well as reducing oxidative stress levels in infected zebrafish. Additionally, Ori promoted the expression of NRF2/HO-1/NQO-1 and activated the AKT/AMPK-α1/GSK-3β signaling pathway, which are both associated with anti-inflammatory and antioxidant effects. In summary, our results demonstrate that Ori exerts inhibitory effects on infection and proliferation in cells and zebrafish, respectively. Additionally, Ori regulates oxidative stress by modulating the NRF2/HO-1/NQO-1 and AKT/AMPK-α1/GSK-3β signaling pathways.
PubMed: 37375489
DOI: 10.3390/pathogens12060799 -
European Journal of Medicinal Chemistry Nov 2023A series of 3-methoxy-2-phenylimidazo[1,2-b]pyridazine derivatives which were highly active against autoluminescent Mycobacterium tuberculosis (Mtb) and Mycobacterium...
A series of 3-methoxy-2-phenylimidazo[1,2-b]pyridazine derivatives which were highly active against autoluminescent Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm) in an in vitro assay were identified. SAR analysis showed that the most active compounds, which included a phenyl group bearing fluoro substituent(s) at C2, a methoxy function at C3, and a benzyl-heteroatom moiety at C6, exhibited in vitro MIC values generally around 0.63-1.26 μM against Mtb and Mm. However, these compounds were inactive against Mtb in vivo (mice), and investigations revealed very short metabolic half-lives (<10 min) when incubated with mouse liver microsomes. Multiple observations of side products produced from oxidative cleavage of the imidazole moiety during the chemical synthesis work suggested that this is a likely metabolic pathway leading to the lack of observed activity in vivo.
Topics: Animals; Mice; Mycobacterium tuberculosis; Antitubercular Agents; Mycobacterium marinum; Pyridazines; Microbial Sensitivity Tests
PubMed: 37524009
DOI: 10.1016/j.ejmech.2023.115637 -
Evolution, Medicine, and Public Health 2023Sex and reproductive status of the host have a major impact on the immune response against infection. Our aim was to understand their impact on host tolerance or...
Sex and reproductive status of the host have a major impact on the immune response against infection. Our aim was to understand their impact on host tolerance or resistance in the systemic infection of . We measured host survival and bacillary load at time of death, as well as expression by quantitative real-time polymerase chain reaction of immune genes (diptericin and drosomycin). We also assessed the impact of metabolic and hormonal regulation in the protection against infection by measuring expression of upd3, impl2 and ecR. Our data showed increased resistance in actively mating flies and in mated females, while reducing their tolerance to infection. Data suggests that Toll and immune deficiency (Imd) pathways determine tolerance and resistance, respectively, while higher basal levels of ecR favours the stimulation of the Imd pathway. A dual role has been found for upd3 expression, linked to increased/decreased mycobacterial load at the beginning and later in infection, respectively. Finally, impl2 expression has been related to increased resistance in non-actively mating males. These results allow further assessment on the differences between sexes and highlights the role of the reproductive status in to face infections, demonstrating their importance to determine resistance and tolerance against infection.
PubMed: 37868078
DOI: 10.1093/emph/eoad029 -
Microbiology Spectrum Aug 2023Among the numerous pathogenic nontuberculous mycobacteria (NTM), which may cause disease in both poikilothermic and homoeothermic organisms, members of the unique clade...
Among the numerous pathogenic nontuberculous mycobacteria (NTM), which may cause disease in both poikilothermic and homoeothermic organisms, members of the unique clade Mycobacterium ulcerans/Mycobacterium marinum (MuMC) may cause disease in both fish and humans. Here, we describe the emergence of Mycobacterium pseudoshottsii, one of the four MuMC members, in Israel. For many years, M. marinum was the dominant NTM that was diagnosed in Israel as a fish pathogen. To the best of our knowledge, this is the first isolation and genomic characterization of infecting edible fish from two different fish species farmed in offshore sea cages in the eastern Mediterranean as well as in a recirculating aquaculture system in Israel. We compared the whole-genome sequences to all available genomic sequences of MuMC in free, publicly accessible databases. Mycobacterium pseudoshottsii was first detected in 1997 in the USA, infecting wild striped bass (Morone saxatilis). Since then, several reports from different countries worldwide have shown its capacity to become established in new regions as well as its pathogenicity to saltwater and euryhaline finfish of different genera. Our phylogenetic analysis revealed that the Mycobacterium ulcerans/Mycobacterium marinum clade (MuMC) is divided into two main branches: one that includes M. marinum and , and the second, which includes other M. marinum isolates as well as two isolates of M. shottsii. Our results reinforce the proposition that the geographical distribution of is much more extensive than is commonly believed. The emergence of in different parts of the world and its pathogenic traits that affect finfish of different genera may be a cause for concern among fish farmers, researchers, and environmental organizations.
Topics: Humans; Animals; Phylogeny; Mycobacterium; Bass; Phenotype; Mycobacterium marinum; Mycobacterium Infections, Nontuberculous; Fish Diseases
PubMed: 37272844
DOI: 10.1128/spectrum.00856-23