Search Results (9)

Mycobacterium avium subsp. hominissuis (MAH) is a zoonotic pathogen with a broad host range and diverse clinical manifestations. We report here the first documented case of MAH-induced fatal vasculitis in zebra finch (Taeniopygia guttata). Histopathological examination revealed acid-fast bacilli within macrophages and endothelial cells, primarily affecting the heart and aorta. Mycobacterial DNA was detected in cloacal swabs from affected finches and environmental samples from their housing facility. PCR targeting the rpoB gene and insertion elements IS1245 and IS901, followed by sequencing, confirmed MAH infection. MAH DNA was identified in 4 of 13 finch cloacal swabs and 7 of 28 environmental samples. This study describes a novel, highly pathogenic manifestation of MAH in birds and underscores the potential for avian involvement in environmental and zoonotic transmission. Full article

Background Members of the Mycobacterium avium complex (MAC) have been documented to cause severe and disseminated infections in dogs, although such cases are sporadically reported. In this study, a comprehensive account of a rare case of generalised lymphadenomegaly caused by a mixed-strain infection with drug- and multidrug-resistant Mycobacterium avium subspecies hominissuis (Mah) in a Maremma sheepdog is presented. Methods Laboratory investigations, as well as the monitoring of the clinical signs displayed by the animal, were conducted throughout the course of a two-year drug therapy (based on rifampicin, azithromycin, and ciprofloxacin) and a two-year post-treatment follow-up period, until the death of the dog. Laboratory examinations included both solid and broth cultures from fine-needle aspiration samples of lymph nodes, molecular typing by 8-locus MIRUVNTR analysis and SNPs typing of five genetic regions (gyrB, rpsA, 3′hsp65, ITS and rpoB), and drug susceptibility testing towards seven antimycobacterial drugs. Results The results indicated the presence of two distinct genotypes of Mah, which exhibited different phenotypic characteristics, such as different drug susceptibility profiles and growth abilities in broth and solid media, suggesting a mixed-strain infection. Resistances to ethambutol alone, to ethambutol and clarithromycin, and to ethambutol, clarithromycin, rifampicin, and doxycycline were detected over the study. Conclusions Although the Mah strains isolated during the course of therapy showed sensitivity to the regiment, the complete eradication of the infection was never achieved. It has been hypothesised that the presence of drug-resistant and multidrug-resistant Mah strains in the animal may have been established at the onset of the infection or soon thereafter. The exposure to therapy has been suggested as a potential factor that could have favoured the growth of resistant strains, thereby rendering the therapy ineffective. The implications that the distinct phenotypic and genotypic profiles of Mah described here may have had for disease dynamics and control are discussed. Full article

Non-tuberculous mycobacteria (NTM) are ubiquitous organisms, of which some, especially those of the Mycobacterium avium complex (MAC), may be opportunistic animal and human pathogens. Infection with NTM can interfere with tuberculosis (TB) diagnosis and induce zoonoses, especially in immunocompromised individuals. Diseases caused by NTM have become more readily recognized; however, they are likely still underestimated. In this study, we identified and genotyped Mycobacterium avium strains that were isolated during TB monitoring among free-living carnivorous animals from southeastern Poland. In 2011–2020, lymph node samples from 192 such animals were tested for mycobacteria. A total of 41 isolates of M. avium strains were detected with the use of IS901, IS900, IS1245, and mycobacterial interspersed repeat unit–variable number tandem repeat (MIRU-VNTR) identification. Thirty-three were identified as M. avium subsp. avium. These strains were derived from 1 beech marten (Martes foina), 1 common buzzard (Buteo buteo), 2 European badgers (Meles meles), 3 wolves (Canis lupus), and 26 red foxes (Vulpes vulpes). One strain isolated from a wolf was identified as M. avium subsp. hominissuis. The results show the widespread occurrence of MAC bacilli in the studied environment and additionally comprise new data on the molecular characteristics of M. avium subspecies carried by free-living southeastern Polish carnivores. Full article

All currently approved antibiotics are being met by some degree of resistance by the bacteria they target. Biofilm formation is one of the crucial enablers of bacterial resistance, making it an important bacterial process to target for overcoming antibiotic resistance. Accordingly, several drug delivery systems that target biofilm formation have been developed. One of these systems is based on lipid-based nanocarriers (liposomes), which have shown strong efficacy against biofilms of bacterial pathogens. Liposomes come in various types, namely conventional (charged or neutral), stimuli-responsive, deformable, targeted, and stealth. This paper reviews studies employing liposomal formulations against biofilms of medically salient gram-negative and gram-positive bacterial species reported recently. When it comes to gram-negative species, liposomal formulations of various types were reported to be efficacious against Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and members of the genera Klebsiella, Salmonella, Aeromonas, Serratia, Porphyromonas, and Prevotella. A range of liposomal formulations were also effective against gram-positive biofilms, including mostly biofilms of Staphylococcal strains, namely Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus saprophyticus subspecies bovis, followed by Streptococcal strains (pneumonia, oralis, and mutans), Cutibacterium acnes, Bacillus subtilis, Mycobacterium avium, Mycobacterium avium subsp. hominissuis, Mycobacterium abscessus, and Listeria monocytogenes biofilms. This review outlines the benefits and limitations of using liposomal formulations as means to combat different multidrug-resistant bacteria, urging the investigation of the effects of bacterial gram-stain on liposomal efficiency and the inclusion of pathogenic bacterial strains previously unstudied. Full article

Non-tuberculosis mycobacteria (NTM) are ubiquitously found throughout the environment. NTM can cause respiratory infections in individuals with underlying lung conditions when inhaled, or systemic infections when ingested by patients with impaired immune systems. Current therapies can be ineffective at treating NTM respiratory infections, even after a long course or with multidrug treatment regimens. NTM, such as Mycobacterium avium subspecies hominissuis (M. avium), is an opportunistic pathogen that shares environments with ubiquitous free-living amoeba and other environmental hosts, possibly their evolutionary hosts. It is highly likely that interactions between M. avium and free-living amoeba have provided selective pressure on the bacteria to acquire survival mechanisms, which are also used against predation by macrophages. In macrophages, M. avium resides inside phagosomes and has been shown to exit it to infect other cells. M. avium’s adaptation to the hostile intra-phagosomal environment is due to many virulence mechanisms. M. avium is able to switch the phenotype of the macrophage to be anti-inflammatory (M2). Here, we have focused on and discussed the bacterial defense mechanisms associated with the intra-phagosome phase of infection. M. avium possesses a plethora of antioxidant enzymes, including the superoxide dismutases, catalase and alkyl hydroperoxide reductase. When these defenses fail or are overtaken by robust oxidative burst, many other enzymes exist to repair damage incurred on M. avium proteins, including thioredoxin/thioredoxin reductase. Finally, M. avium has several oxidant sensors that induce transcription of antioxidant enzymes, oxidation repair enzymes and biofilm- promoting genes. These expressions induce physiological changes that allow M. avium to survive in the face of leukocyte-generated oxidative stress. We will discuss the strategies used by M. avium to infect human macrophages that evolved during its evolution from free-living amoeba. The more insight we gain about M. avium’s mode of pathogenicity, the more targets we can have to direct new anti-virulence therapies toward. Full article

Mycobacterium avium complex (MAC), a collection of mycobacterial species representing nontuberculous mycobacteria, are characterized as ubiquitous and opportunistic pathogens. The incidence and prevalence of infectious diseases caused by MAC have been emerging globally due to complications in the treatment of MAC-pulmonary disease (PD) in humans and the lack of understating individual differences in genetic traits and pathogenesis of MAC species or subspecies. Despite genetically close one to another, mycobacteria species belonging to the MAC cause diseases to different host range along with a distinct spectrum of disease. In addition, unlike Mycobacterium tuberculosis, the underlying mechanisms for the pathogenesis of MAC infection from environmental sources of infection to their survival strategies within host cells have not been fully elucidated. In this review, we highlight unique genetic and genotypic differences in MAC species and the virulence factors conferring the ability to MAC for the tactics evading innate immune attacks of host cells based on the recent advances in genetic analysis by exemplifying M. avium subsp. hominissuis, a major representative pathogen causing MAC-PD in humans. Further understanding of the genetic link between host and MAC may contribute to enhance host anti-MAC immunity, but also provide novel therapeutic approaches targeting the pangenesis-associated genes of MAC. Full article

Mycobacterium avium subspecies hominissuis (MAH) is an opportunistic intracellular pathogen causing infections in individuals with chronic lung conditions and patients with immune-deficient disorders. The treatment of MAH infections is prolonged and outcomes many times are suboptimal. The reason for the extended treatment is complex and reflects the inability of current antimicrobials to clear diverse phenotypes of MAH quickly, particularly, the subpopulation of susceptible but drug-tolerant bacilli where the persistent fitness to anti-MAH drugs is stimulated and enhanced by the host environmental stresses. In order to enhance the pathogen killing, we need to understand the fundamentals of persistence mechanism and conditions that can initiate the drug-tolerance phenotype in mycobacteria. MAH can influence the intracellular environment through manipulation of the metal concentrations in the phagosome of infected macrophages. While metals play important role and are crucial for many cellular functions, little is known how vacuole elements influence persistence state of MAH during intracellular growth. In this study, we utilized the in vitro model mimicking the metal concentrations and pH of MAH phagosome at 1 h and 24 h post-infection to distinguish if metals encountered in phagosome could act as a trigger factor for persistence phenotype. Antibiotic treatment of metal mix exposed MAH demonstrates that metals of the phagosome environment can enhance the persistence state, and greater number of tolerant bacteria is recovered from the 24 h metal mix when compared to the viable pathogen number in the 1 h metal mix and 7H9 growth control. In addition, bacterial phenotype induced by the 24 h metal mix increases MAH tolerance to macrophage killing in TNF-α and IFN-γ activated cells, confirming presence of persistent MAH in the 24 h metal mix condition. This work shows that the phagosome environment can promote persistence population in MAH, and that the population differs dependent on a concentration of metals. Full article

Background: Mycobacteria of the Mycobacterium avium complex (MAC) pose a significant risk to zoological collections. Mycobacterium avium subspecies paratuberculosis (MAP) is a member of MAC and the causative agent of Johne’s disease. Despite many reports in animals kept in zoological gardens, systemic surveillance has rarely been reported. Methods: In this study, archived serum samples collected from animal species at the Wilhelma Zoological and Botanical Gardens in Stuttgart, Germany, were screened for the presence of antibodies against MAC and MAP. In addition, molecular investigations were performed on necropsy, fecal, and environmental samples. Results: In total, 30/381 serum samples of various mammalian species were positive for MAC antibodies in ELISA, while one sample of a reticulated giraffe (Giraffa camelopardalis reticulata) was positive in MAP-specific ELISA. Samples from many species were positive in pan-Mycobacterium real-time PCR (40/43 fecal samples, 27/43 environmental samples, and 31/90 necropsy samples). Surprisingly, no sample was positive in the MAP-specific molecular assays. However, two environmental samples from primate enclosures were positive in Mycobacterium avium subspecies hominissuis (MAH)-specific real-time PCR. Conclusions: The results reveal serological indications of MAC infections in the zoological collection. However, the presence of a MAP-contaminated environment by a high-shedding individual animal or MAP-infected population is unlikely. Full article

Mycobacterium avium subspecies hominissuis (MAH) is an opportunistic pathogen that is ubiquitous in the environment and often isolated from faucets and showerheads. MAH mostly infects humans with an underlying disease, such as chronic pulmonary disorder, cystic fibrosis, or individuals that are immunocompromised. In recent years, MAH infections in patients without concurrent disease are increasing in prevalence as well. This pathogen is resistant to many antibiotics due to the impermeability of its envelope and due to the phenotypic resistance established within the host macrophages, making difficult to treat MAH infections. By screening a MAH transposon library for mutants that are susceptible to killing by reactive nitrogen intermediaries, we identified the MAV_4644 (MAV_4644:Tn) gene knockout clone that was also significantly attenuated in growth within the host macrophages. Complementation of the mutant restored the wild-type phenotype. The MAV_4644 gene encodes a dual-function protein with a putative pore-forming function and ADP-ribosyltransferase activity. Protein binding assay suggests that MAV_4644 interacts with the host lysosomal peptidase cathepsin Z (CTSZ), a key regulator of the cell signaling and inflammation. Pathogenic mycobacteria have been shown to suppress the action of many cathepsins to establish their intracellular niche. Our results demonstrate that knocking-down the cathepsin Z in human macrophages rescues the attenuated phenotype of MAV_4644:Tn clone. Although, the purified cathepsin Z by itself does not have any killing effect on MAH, it contributes to bacterial killing in the presence of the nitric oxide (NO). Our data suggest that the cathepsin Z is involved in early macrophage killing of MAH, and the virulence factor MAV_4644 protects the pathogen from this process. Full article