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Nature Communications Mar 2024Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent...
Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.
Topics: Humans; Mycobacterium abscessus; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous; Macrolides; Phylogeny; Persistent Infection; Reinfection; Drug Resistance, Bacterial; Genomics; Microbial Sensitivity Tests
PubMed: 38548737
DOI: 10.1038/s41467-024-46552-w -
Journal of Microbiological Methods May 2024The CRISPRi system using dCas9 from Streptococcus thermophilus developed for Mycobacterium tuberculosis and M. smegmatis was modified to allow gene knock-out in M....
The CRISPRi system using dCas9 from Streptococcus thermophilus developed for Mycobacterium tuberculosis and M. smegmatis was modified to allow gene knock-out in M. abscessus. Efficacy of the knock-out system was evaluated by applying deletions and insertions to the mps1 gene. A comparative genomic analysis of mutants and wild type validated the target specificity.
Topics: Mycobacterium abscessus; CRISPR-Cas Systems; Streptococcus thermophilus; Mycobacterium tuberculosis
PubMed: 38548070
DOI: 10.1016/j.mimet.2024.106924 -
Microorganisms Mar 2024complex (MABC), a rapidly growing , is one of the most common causes of non-tuberculous mycobacteria (NTM) infections in the United States of America, and it has been... (Review)
Review
complex (MABC), a rapidly growing , is one of the most common causes of non-tuberculous mycobacteria (NTM) infections in the United States of America, and it has been associated with a wide spectrum of infections in immunocompetent and immunosuppressed individuals. Eradicating MABC is very challenging, even with prolonged combination therapies. The management of MABC infections in solid organ transplant (SOT) patients is usually complex given their net state of immunosuppression, associated comorbidities, and potential drug-drug interactions, among other things. In this manuscript, we discussed the antimicrobial management of pulmonary and extrapulmonary MABC infections. In addition, we reviewed promising novel therapies such as clofazimine, omadacycline, bedaquiline, and inhaled tigecycline that could join the existing antimicrobial armamentarium to fight this infection associated with significant morbidity and mortality. However, further studies are needed, especially among the immunocompromised host.
PubMed: 38543646
DOI: 10.3390/microorganisms12030596 -
Microorganisms Feb 2024This study aimed to evaluate the antibacterial, leishmanicidal, and cytotoxic potential of metabolites produced by bacteria isolated from rhizosphere soil samples. The...
This study aimed to evaluate the antibacterial, leishmanicidal, and cytotoxic potential of metabolites produced by bacteria isolated from rhizosphere soil samples. The bacterium was identified by genome sequencing as . A preliminary screening was carried out for the antimicrobial activity of , demonstrating activity against ATCC 6538, ATCC 27010, ATCC 27012, and , with inhibition halos of sizes 25, 36, 29, and 33 mm, respectively. To obtain secondary metabolites, the bacteria were subjected to submerged fermentation, and the metabolites were extracted using the liquid-liquid method with ethyl acetate. There was a similar MIC for and the two strains of , reaching a concentration of 12.5 µg/mL, while that of was 0.048 µg/mL. Assays for leishmanicidal activity and cytotoxicity against HEp-2 cells and red blood cells were performed. The metabolite showed an IC of 9.0 ± 0.9 µg/mL and CC of 221.2 ± 7.0 µg/mL. This metabolite does not have hemolytic activity and is more selective for parasites than for mammalian cells, with a selectivity index of 24.6. Thus, the studied metabolite may be a strong candidate for the development of less toxic drugs to treat diseases caused by pathogens.
PubMed: 38543527
DOI: 10.3390/microorganisms12030476 -
Microbiology Spectrum May 2024To address intracellular mycobacterial infections, we developed a cocktail of four enzymes that catalytically attack three layers of the mycobacterial envelope. This...
To address intracellular mycobacterial infections, we developed a cocktail of four enzymes that catalytically attack three layers of the mycobacterial envelope. This cocktail is delivered to macrophages, through a targeted liposome presented here as ENTX_001. Endolytix Cocktail 1 (EC1) leverages mycobacteriophage lysin enzymes LysA and LysB, while also including α-amylase and isoamylase for degradation of the mycobacterial envelope from outside of the cell. The LysA family of proteins from mycobacteriophages has been shown to cleave the peptidoglycan layer, whereas LysB is an esterase that hydrolyzes the linkage between arabinogalactan and mycolic acids of the mycomembrane. The challenge of gaining access to the substrates of LysA and LysB provided exogenously was addressed by adding amylase enzymes that degrade the extracellular capsule shown to be present in . This enzybiotic approach avoids antimicrobial resistance, specific receptor-mediated binding, and intracellular DNA surveillance pathways that limit many bacteriophage applications. We show this cocktail of enzymes is bactericidal against both rapid- and slow-growing nontuberculous mycobacteria (NTM) as well as strains. The EC1 cocktail shows superior killing activity when compared to previously characterized LysB alone. EC1 is also powerfully synergistic with standard-of-care antibiotics. In addition to killing of NTM, ENTX_001 demonstrates the rescue of infected macrophages from necrotic death by and . Here, we demonstrate shredding of mycobacterial cells by EC1 into cellular debris as a mechanism of bactericide.IMPORTANCEThe world needs entirely new forms of antibiotics as resistance to chemical antibiotics is a critical problem facing society. We addressed this need by developing a targeted enzyme therapy for a broad range of species and strains within mycobacteria and highly related genera including nontuberculous mycobacteria such as , , as well as . One advantage of this approach is the ability to drive our lytic enzymes through encapsulation into macrophage-targeted liposomes resulting in attack of mycobacteria in the cells that harbor them where they hide from the adaptive immune system and grow. Furthermore, this approach shreds mycobacteria independent of cell physiology as the drug targets the mycobacterial envelope while sidestepping the host range limitations observed with phage therapy and resistance to chemical antibiotics.
Topics: Mycobacterium tuberculosis; Mycobacteriophages; Macrophages; Humans; Nontuberculous Mycobacteria; Liposomes; Anti-Bacterial Agents; Peptidoglycan; Microbial Sensitivity Tests; Endopeptidases; Galactans
PubMed: 38534149
DOI: 10.1128/spectrum.03534-23 -
Clinical Microbiology and Infection :... Jun 2024Antibiotic treatment of Mycobacterium abscessus disease is toxic and poorly effective and lacks a firm evidence base. Dual β-lactam and β-lactam/β-lactamase inhibitor... (Review)
Review
BACKGROUND
Antibiotic treatment of Mycobacterium abscessus disease is toxic and poorly effective and lacks a firm evidence base. Dual β-lactam and β-lactam/β-lactamase inhibitor combinations may be interesting leads to improve treatment outcomes.
OBJECTIVES
To summarize the current preclinical studies on dual β-lactam and β-lactam/β-lactamase inhibitor combinations against M. abscessus.
SOURCES
We performed a literature search using the National Center for Biotechnology Information's PubMed interface with additional snowball sampling.
CONTENT
Select combinations of β-lactam antibiotics, as well as β-lactam/β-lactamase inhibitor combinations show promising in vitro activity and synergy against M. abscessus. β-Lactam antibiotics differ in their ability to reach and interfere with their targets and their resistance to the M. abscessus β-lactamase. The synergy is typically observed for combinations of β-lactam antibiotics or a β-lactam antibiotic with a β-lactamase inhibitor. No additional killing capacity was demonstrated in three-drug combinations of synergistic β-lactam antibiotics and a β-lactamase inhibitor. The efficacy of select dual β-lactam antibiotics and β-lactam/β-lactamase inhibitor combinations is retained in intracellular infection assays and mouse models, but no combination has a complete preclinical portfolio.
IMPLICATIONS
Future clinical strategies should entail either dual β-lactam or β-lactam/β-lactamase inhibitor combinations. Imipenem-ceftaroline and an all-oral tebipenem-avibactam combination are promising leads but still require a complete preclinical portfolio, target product profiles as well as clinical trial confirmation.
Topics: Mycobacterium abscessus; beta-Lactams; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous; beta-Lactamase Inhibitors; Humans; Treatment Outcome; Drug Therapy, Combination; Drug Synergism; Animals; Microbial Sensitivity Tests
PubMed: 38527611
DOI: 10.1016/j.cmi.2024.03.019 -
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 -
Clinical, Cosmetic and Investigational... 2024is ubiquitous in the environment and seldom causes infections in immunocompetent individuals. However, skin and soft tissue infections caused by have been reported in...
AIM
is ubiquitous in the environment and seldom causes infections in immunocompetent individuals. However, skin and soft tissue infections caused by have been reported in recent years. Additionally, the cutaneous infections or outbreaks post cosmetic surgery caused by have been increasing due to the popularity of plastic surgery. The main modes of transmission are through contaminated saline, disinfectants, or surgery equipment, as well as close contact between patients. This article describes three patients who were admitted to our hospital between November 2019 and October 2020. They presented with long-term non-healing wounds caused by infection after undergoing plastic surgery. Symptoms presented by the three patients included swelling, ulceration, secretion, and pain. After identification of with Ziehl-Neelsen staining and MALDI-TOF MS system, the patients were treated with surgical debridement and clarithromycin.
CONCLUSION
It is important to note that a long-term wound that does not heal, especially after plastic surgery, should raise suspicion for infection. The infection mechanism in these three patients may have been due to exposure to surgical equipment that was not properly sterilized or due to poor sterile technique by the plastic surgeon. To prevent such infections, it is important to ensure proper sterilization of surgical equipment and saline.
PubMed: 38505806
DOI: 10.2147/CCID.S445175 -
Heliyon Mar 2024To identify essential oils (EOs) active against non-growing stationary phase and multidrug-resistant strains.
PURPOSE
To identify essential oils (EOs) active against non-growing stationary phase and multidrug-resistant strains.
METHODS
The activity of EOs against both stationary and log phase was evaluated by colony forming unit (CFU) assay and minimum inhibitory concentration (MIC) testing.
RESULTS
We assessed the activity of 80 EOs against stationary phase and found 12 EOs (Cinnamon, Satureja montana, Palmarosa, Lemon eucalyptus, Honey myrtle, Combava, Health shield, Mandarin, Thyme, Rosewood, Valerian Root and Basil) at 0.5% concentration to be active against both growing and non-growing stationary phase Among them, Satureja montana essential oil and Palmarosa essential oil could eliminate all stationary phase at 0.125% and Cinnamon essential oil could eliminate stationary phase bacteria at 0.063% after 1-day treatment. Interestingly, these EOs also exhibited promising activity against multidrug-resistant clinical strains.
CONCLUSIONS
Our study indicates that some EOs display outstanding effectiveness against both drug susceptible and multidrug-resistant isolates. These findings may be significant for the treatment of persistent infections.
PubMed: 38463856
DOI: 10.1016/j.heliyon.2024.e27073 -
International Journal of Infectious... Jun 2024To investigate the spatial heterogeneity of nontuberculous mycobacterial pulmonary disease (NTM-PD) in Shanghai.
OBJECTIVE
To investigate the spatial heterogeneity of nontuberculous mycobacterial pulmonary disease (NTM-PD) in Shanghai.
METHODS
A population-based retrospective study was conducted using presumptive pulmonary tuberculosis surveillance data of Shanghai between 2010 and 2019. The study described the spatial distribution of NTM-PD notification rates, employing hierarchical Bayesian mapping for high-risk areas and the Getis-Ord Gi* statistic to identify hot spots and explore associated factors.
RESULTS
Of 1652 NTM-PD cases, the most common species was Mycobacterium kansasii complex (MKC) (41.9%), followed by Mycobacterium avium complex (MAC) (27.1%) and Mycobacterium abscessus complex (MABC) (16.2%). MKC-PD patients were generally younger males with a higher incidence of pulmonary cavities, while MAC-PD patients were more often farmers or had a history of tuberculosis treatment. MKC-PD hot spots were primarily located in the areas alongside the Huangpu River, while MAC-PD hot spots were mainly in the western agricultural areas. Patients with MKC-PD and MAC-PD exhibited a higher risk of spatial clustering compared to those with MABC-PD.
CONCLUSIONS
Different types of NTM-PD exhibit distinct patterns of spatial clustering and are associated with various factors. These findings underscore the importance of environmental and host factors in the epidemic of NTM-PD.
Topics: Humans; Male; Mycobacterium Infections, Nontuberculous; China; Female; Retrospective Studies; Middle Aged; Aged; Adult; Mycobacterium kansasii; Nontuberculous Mycobacteria; Bayes Theorem; Incidence; Spatial Analysis; Risk Factors; Young Adult; Mycobacterium avium Complex; Tuberculosis, Pulmonary; Mycobacterium abscessus
PubMed: 38461931
DOI: 10.1016/j.ijid.2024.107001