Review Article

JOURNAL OF BACTERIOLOGY AND VIROLOGY. 31 December 2024. 273-283
https://doi.org/10.4167/jbv.2024.54.4.273

ABSTRACT


MAIN

INTRODUCTION

The genus Mycobacterium includes the Mycobacterium tuberculosis (Mtb) complex, Mycobacterium leprae, and non-tuberculous mycobacteria (NTM) (1). Tuberculosis (TB) remains a leading cause of mortality worldwide, necessitating ongoing research into vaccines and pathogenic mechanisms to enhance control measures and ultimately eradicate TB (2, 3). Despite the significant focus on TB, there is growing concern regarding the rising incidence of NTM infections (4, 5, 6). Unlike Mtb, which survives in the human body and is transmitted between people, NTM are widely distributed in nature, including rivers and soil, and are not usually transmitted between people through respiratory infections (7). Although TB incidence is declining in industrialized countries, NTM infections are steadily increasing (5). However, because NTM include many more species than Mtb, research on each of these bacteria has been relatively limited compared to TB, despite the potential risks and applications associated with NTM (8). Therefore, further study is needed on the pathogenicity, treatment methods, and potential applications of each NTM strain.

Mycobacterium paragordonae (Mpg) is a recently identified species first described in 2014 (9). Mpg presents notable potential as a vaccine candidate due to its unique characteristics, including temperature sensitivity and adaptability to diverse environments, including clinical settings (10, 11, 12, 13, 14). It has been proposed as a novel live vaccine to prevent mycobacterial infections and has demonstrated promising results in inducing immune responses in various studies (10, 14). Furthermore, one of the characteristics of BCG heterologous immunity—which acts as innate immune memory—has also been observed in Mpg, activating the innate immune response by leveraging type I interferons (IFN-I) from dendritic cells (DC), suggesting its potential application across various disease fields (13, 15). Mpg, which demonstrates these beneficial properties, exhibits a more adaptive intracellular lifestyle within amoeba, which are aquatic protozoa, compared to other mycobacteria, leading to its reporting in water-related infections (16). Mpg rarely appears in clinical case studies and a few infection cases will be discussed in this review (17, 18, 19, 20, 21).

This review aims to provide a comprehensive summary of the current research status of Mpg. By compiling published literature, we aim to highlight key findings and emphasize the potential applications of Mpg in various research fields, including clinical applications and vaccine development.

PHENOTYPIC AND PHYLOGENETIC CHARACTERISTICS OF MPG

Mpg was first isolated from a clinical sample of a patient’s sputum with symptomatic pulmonary infections during an investigation involving the hsp65-sequence-based identification of Korean clinical isolates. The strain, designated as 49061T, was initially suspected to be M. gordonae due to its phenotypic similarities. Although strain 49061T shared several phenotypic traits with M. gordonae, including being a rod-shaped and acid-fast bacterium with curved bacilli without spores or filaments observable by microscopy, there were notable differences. Unlike M. gordonae, which grows optimally at 37°C and produces yellow or white colonies, strain 49061T exhibited optimal growth at lower temperatures of 25-30°C and failed to grow at 37°C on commonly used Middlebrook 7H10 agar slants. The colonies of strain 49061T were smooth and orange in color, distinguishing it from M. gordonae(9).

In some studies, it has been reported that Mpg grows at 37°C on 7H11 agar, Lowenstein-Jensen (LJ) media, and in the BD BACTEC MGIT 960 system (22, 23, 24). Considering this, it is likely that these differences may be attributable to the composition of each medium. First, 7H11 agar is an enriched medium that includes casein hydrolysate added to 7H10 agar, providing additional nutrients (25). LJ media primarily contains eggs, which supply proteins and lipids, while the BD BACTEC MGIT 960 system utilizes modified Middlebrook 7H9 liquid media with casein peptone (26, 27). Overall, the studies reporting Mpg growth at 37°C appear to involve media with higher nutrient content, such as casein, compared to 7H9 broth or 7H10 agar, where Mpg has previously shown temperature sensitivity. However, the specific nutrient components that influence the temperature-sensitive (TS) growth characteristics of Mpg have yet to be determined. Further research on this issue could advance our understanding not only of Mpg but also of TS bacteria more broadly.

Genomic analysis was performed to definitively determine its taxonomic status. Phylogenetic analyses based on 16S rRNA, hsp65, and rpoB gene sequences indicated it as a distinct species. DNA-DNA hybridization assay also supported this classification, leading to the recognition of strain 49061T as a novel species, formally named Mycobacterium paragordonae (type strain 49061T = JCM 18565T = KCTC 29126T) in 2014 (9).

Biochemical analysis revealed unique profiles for strain 49061T, demonstrating tolerance to thiophene-2-carboxylic acid hydrazide (TCH) and lack of growth on media containing high concentrations of p-nitrobenzoate (PNB), 5% sodium chloride, picric acid, or ethambutol. Additionally, strain 49061T didn’t accumulate niacin or reduce nitrate, which are typical reactions for M. gordonae (9).

ANTIBIOTIC SUSCEPTIBILITY OF MPG AND ITS USE FOR DRUG SCREENING

Mpg shows high susceptibility to a broad spectrum of antibiotics, making it a valuable organism for antibiotic screening. The high susceptibility of Mpg allows it to efficiently eliminate ineffective compounds, making it particularly useful in the early stages of drug screening. This advantage is also important when only small amounts of compounds are available for testing.

In studies confirming the susceptibility of Mpg to various antibiotics using the SLOMYCO Sensititre panel, it showed significantly lower minimum inhibitory concentrations (MICs) for antibiotics such as ciprofloxacin, clarithromycin, isoniazid, moxifloxacin, rifampin, and streptomycin compared to closely related species like M. marinum and M. gordonae. The MICs for Mpg were being 4-8 times lower, highlighting its potential as a model organism for antibiotic research (28).

Utilizing its high sensitivity to antibiotics, a recombinant Mpg strain expressing a luciferase reporter gene (rMpg-LuxG13) was developed to improve the efficiency and accuracy of antibiotic screening assays. The rMpg-luxG13 facilitates real-time monitoring of bacterial viability through luminescence measurements, enabling high-throughput screening. This drug screening model was developed using both amoeba-based and in vitro direct application systems. The amoeba-based system was conducted by infecting Acanthamoeba castellanii with the rMpg-LuxG13 strain to assess their interactions. The amoebae infected for 2 hours at 28 ˚C were cultured in PYG medium containing 10 μM amikacin to remove extracellular bacteria, and subsequently used for drug screening. Studies have shown that antibiotics such as rifampin, isoniazid, clarithromycin, and ciprofloxacin effectively inhibit the growth of rMpg-LuxG13, demonstrating the strain’s utility in antibiotic screening and drug discovery (28).

POTENTIAL OF MPG AS A LIVE TB VACCINE

The unique characteristics of Mpg, such as its susceptibility to various antibiotics and TS growth, highlight its potential as a safe live vaccine candidate. Unlike BCG, Mpg retains the RD1 region, which is crucial for presenting antigens related to immune system resistance and evasion (16). When BCG was complemented with key RD1 genes, the complemented BCG exhibited enhanced protection against Mtb infections in preclinical models (29). Furthermore, Mpg harbors all five ESX loci (ESX-1, ESX-2, ESX-3, ESX-4, and ESX-5) found in Mtb, which may contribute to enhanced protection against TB (16).

Studies have demonstrated that Mpg can elicit robust immune responses surpassing those of BCG in mouse models. Mpg activates Th1-related cytokines such as IFN-γ and IL-12, essential for an effective immune response against mycobacterial infections like M. abscessus and Mtb, and reduces IL-10 expression associated with an anti-inflammatory response compared to BCG. Additionally, Mpg enhances DC maturation, evidenced by elevated levels of MHC II, CD40, CD80, and CD86, increasing their migratory capacity due to high CCR7 expression and ability to proliferate T cells, suggesting significant implications for developing more effective TB vaccines (10).

Mpg also shows promise as a booster vaccine. In countries where TB is prevalent, most individuals have completed BCG vaccination for TB prevention (30). Therefore, there is considerable interest in booster vaccines that can enhance the weakened immune response in adults following the initial BCG prime. When used as a booster following a BCG prime, Mpg elicited higher cell-mediated immune responses, such as elevated IFN-γ expression and reduced lung inflammation in mouse models (10). Additionally, the use of Mpg in biodegradable microneedle patches (MNP) has further demonstrated its potential as a non-invasive vaccine. Mpg-loaded MNPs applied to mouse skin induced significant immune cell recruitment into the dermis, which was not seen with subcutaneous administration (14). Among the recruited cells, there was a substantial increase in MHC II+ langerin+ cells and Ki-67+ langerin+ cells, which possess migratory capacity and play a key role in initiating T cell-mediated immune responses (31, 32). As a result, higher proportions of IFN-γ and TNF-α-secreting cells were observed in lymph nodes, highlighting its efficacy as a vaccine delivery method. Following a BCG prime, boosting with the Mpg-MNP method demonstrated protective efficacy against the virulent Mtb K-strain, a member of the Beijing strain family (14, 33). These results suggest that Mpg has potential as a novel live attenuated bacterial TB vaccine that could serve as an improved prime vaccine replacing BCG and as a booster vaccine.

HETEROLOGOUS VACCINE POTENTIAL AGAINST DIVERSE PATHOGENS AND USE OF RECOMBINANT MPG FOR VACCINE DELIVERY SYSTEMS

Heterologous vaccination strategies, which enhance innate immune responses to provide broad protection against various pathogens, have shown promise with Mpg (15). Like BCG, which is well-known for its heterologous vaccination effect, Mpg has demonstrated the ability to elicit strong immune responses not only against TB but also against other pathogens like Candida albicans, Staphylococcus aureus, and Escherichia coli (34, 35, 36, 37, 38, 39, 40). This broad-spectrum protection underscores Mpg’s potential as a versatile vaccine candidate. Notably, in SCID (Severe Combined Immunodeficient) mice, which are B-and T-cell deficient, Mpg demonstrated higher protective efficacy compared to BCG, confirming its potential as a stronger heterologous vaccine. Its heterologous vaccine efficacy is mainly attributed to the presence of cyclic di-GMP found in live Mpg, which can play a crucial role in the activation of innate immune cells via induction of IFN-I production (13). The cyclic di-GMP acts as a viability-associated pathogen-associated molecular pattern (vita-PAMP) to induce IFN-I through a stimulator of interferon genes (STING)-mediated endoplasmic reticulum stress response in DC (41). As a result of IFN-I production by DCs, the adaptive memory properties of NK cells are activated, leading to effective immune responses even to secondary stimuli (13, 42, 43).

Given its ability to induce strong immune responses, Mpg has been used to create recombinant forms that express heterologous antigens. Research into vaccine delivery systems using these recombinant Mpg strains has yielded promising results. For instance, recombinant Mpg strains expressing HIV-1 p24 antigens have shown higher T cell proliferation and cytotoxic T lymphocyte (CTL) activity compared to recombinant BCG expressing the same antigens (12). Similarly, immunization with recombinant Mpg expressing the receptor-binding domain (RBD) of SARS-CoV-2 has shown potential in activating immune responses against COVID-19, reducing viral load in SARS-CoV-2-infected cell models, and enhancing in vitro DC activation, indicating its utility in developing vaccines for various infectious diseases (11).

IMMUNOTHERAPY FOR CANCER

Mpg has shown significant promise in cancer immunotherapy as well as in treating infectious diseases. Heat-killed Mpg (HK-Mpg) has demonstrated notable antitumor effects in preclinical models, reducing tumor incidence and size and improving survival rates. These effects are attributed to its ability to strongly induce immune responses by promoting DC maturation and IL-12 production, which are critical for skewing the immune response towards a Th1 profile and activating natural killer (NK) cells (44).

Combining HK-Mpg with conventional chemotherapeutic agents such as cisplatin has shown enhanced efficacy, suggesting that Mpg can potentiate the effects of existing cancer treatments. HK-Mpg has been particularly effective in inducing T-cell responses, including the activation of CTLs and the production of TNF-α, both of which are pivotal in targeting and eliminating cancer cells (44). The ability of HK-Mpg to induce a strong immune response, combined with its synergistic effects when used alongside chemotherapy, positions it as a promising candidate for cancer immunotherapy and an adjunctive immunotherapy approach.

ENVIRONMENTAL ADAPTABILITY AND CLINICAL IMPLICATIONS OF MPG

Mpg has demonstrated remarkable environmental adaptability, particularly in aquatic environments. This adaptability is primarily attributed to its unique genomic features and survival mechanisms that enable it to thrive under diverse conditions. Below, we explore various documented cases of Mpg presence in water systems, providing a detailed overview of its survival strategies and public health implications.

Genomic Characteristics of Mpg

Mpg can survive in a variety of aquatic environments, which has been proven in several studies (24, 45). The increasing frequency of isolation of Mpg from aquatic systems has led to the hypothesis that free-living amoeba systems are likely natural reservoirs of Mpg. A study comparing the intracellular viability of Mpg, M. gordonae, and M. marinum within A. castellanii by counting colony-forming units (CFUs) over seven days showed that Mpg survived at significantly higher levels than M. marinum and M. gordonae, suggesting that Mpg may possess enhanced resistance to phagocytic process after infecting amoeba (16).

A significant feature of the Mpg genome is its massive acquisition of Type VII Secretion System (T7SS)-related genes, which is predicted to have influenced its adaptation to an intracellular lifestyle within environmental predators such as free-living amoebae (16). The genome of Mpg contains all five types of ESX loci, similar to pathogenic species like TB. However, the ESX-2 locus of Mpg is split into two separate regions within its genome, unlike the contiguous arrangement in TB (46). Additionally, Mpg possesses plasmid-encoded ESX systems, including ESX-P5 on plasmid pMpg-1 and an ESX-2-like system on plasmid pMpg-2. This unique genomic configuration, resulting from lateral gene transfer and genomic rearrangements, highlights the adaptation of Mpg to free-living amoebae and its enhanced intracellular survival capacity (16).

Documented Cases in Water Systems

Several studies have demonstrated that Mpg is found in hospital water systems, drinking water, shower water, and even cultured koi (Cyprinus carpio) (18, 19, 20, 24, 47, 48, 49). The consistent detection of Mpg in hospital water sources suggests that it can thrive in aquatic environments, adapting to various conditions and demonstrating high survival rates in such water systems. These findings underscore the importance of Mpg in infection control and water quality management.

Water Supply System: The increasing frequency of clinical isolation of NTM after hospital reconstruction and renovation at Miyazaki University Hospital in Japan prompted an analysis of the potential relationship between NTM and the hospital water supply system. During the outbreak investigation from April to July 2015, Mpg was found in 26.1% of 69 environmental samples. The investigation revealed a significant presence of NTM in recently replaced aerators/rectifiers. Removing these devices and preventing patients from consuming tap water resulted in a decrease in Mpg-positive samples (19).

Shower Water and Indoor Air: A study conducted in the United States showed that shower water contributes significantly to the bacterial community in indoor air and transmits NTM during showering. The dominant NTM species in shower water were M. mucogenicum and Mpg. Mpg accounted for 74.5% and 64.5% of NTM species during showers using rain showerheads and massage showerheads, respectively. The aerosolization of NTM during showering poses a potential infection risk. To minimize exposure, it is recommended to clean showerheads regularly and use water filters (47).

Hospital Water Sources in Iran: A review paper summarizing NTM finding in hospital water sources from various cities in Iran from 2016 to 2020 reported a varied presence of NTMs, including Mpg. Mpg was recorded in three studies, with a prevalence of 21.111% in samples from Isfahan, 6.251% in samples from Tabriz, and 2.321% in samples from Tehran (18, 24, 48). The high prevalence of NTM, including Mpg, highlights the need for rigorous water quality monitoring (20).

Cultured Koi Carp: Mpg has been reported to be isolated from naturally occurring carp exhibiting lethargy, weakness, and pinhead-shaped bodies in aquaculture ponds in Niigata, Japan. Mpg, along with two other Mycobacterium species, caused mycobacteriosis in carp. This suggests that Mpg may be transferred from aquatic environments to aquaculture environments, underscoring the need for regular monitoring and the development of effective antibiotics and vaccines (49).

Clinical Implications

Mpg infection in humans is known to be relatively rare. According to a cohort study in China, Mpg was isolated from only 8 out of 1,730 NTM samples (0.46%) (23). In most cases, it presents with symptoms similar to common NTM infections, such as coughing, sputum production, and pulmonary disease. However, several cases have been reported with different symptoms (21, 50, 51, 52, 53, 54, 55). Documented clinical cases include peritonitis, pericarditis, hemoptysis, Crohn’s disease, lumbar infection, and cervical lymphadenitis (Table 1). These occurrences are sporadic, and most reported cases involve immunocompromised individuals or specific hospital settings. The following are reported Mpg clinical infection case and their symptoms.

Table 1.

Reported Mpg Clinical Infection Cases

Gender
/Age
Pre-existing Conditions Symptoms Diagnostic Methods Treatment Regimen Treatment Duration Outcome Country/ Publication year Ref
Male
/55
End-stage kidney disease due to diabetic nephropathy Abdominal pain, cloudy peritoneal dialysate effluent PD effluent culture, Mycobacteria growth indicator tube Amikacin, Azithromycin, Ethambutol 10 weeks Died of ischemic heart disease Hong Kong
/2017
(21)
Female
/60
Hypothyroidism, dyslipidemia Chest pain, hypoxia Echocardiogram, CT scan, Pericardiocentesis, Mycobacterial culture Ethambutol, Ciprofloxacin, Doxycycline 12 months Stable Canada
/2023
(50)
Male
/44
Crohn’s Disease Abdominal pain, non-bloody diarrhea Colonoscopy, CT scan Mesalamine, Isoniazid, Rifampin 5 months Improved United States
/2022
(51)
Female
/54
None Malaise, hemoptysis, diffuse rhonchi in lungs Chest X-ray, CT, Bronchoalveolar lavage, Acid-fast bacilli culture Azithromycin, Ceftriaxone No Data Lost follow-up United States
/2019
(52)
Male
/53
None Lumbar pain MRI, Biopsy, Culture Rifampin, Ethambutol,
Azithromycin,
Moxifloxacin
1 month Improved China
/2021
(53)
Female
/20s
None Enlarged, mobile right cervical lymph node, pain on swallowing, slightly tender Biopsy, bloodwork, ultrasound, CT scan, culture Amoxicillin/clavulanate, ciprofloxacin, ertapenem, clindamycin, clarithromycin 3 months Resolved Canada
/2022
(54, 55)

Peritonitis: A 55-year-old man on continuous ambulatory peritoneal dialysis (CAPD) developed peritonitis caused by Mpg. He presented with cloudy peritoneal dialysate and abdominal pain. Initial treatment with intraperitoneal cefazolin and cefepime was temporarily effective, but symptoms recurred. Mpg was identified after 2 weeks of incubation. Despite switching to intravenous antibiotics and removing the catheter, the patient did not improve significantly and ultimately succumbed to ischemic heart disease after 10 weeks (21).

Pericarditis: A 60-year-old woman with hypothyroidism and dyslipidemia presented with chest pain and hypoxia, diagnosed as Mpg-associated pericarditis with pericardial masses. Mpg was later found in the pericardial fluid. After 12 months of treatment with ethambutol, ciprofloxacin, and doxycycline, her symptoms and pericardial effusion significantly improved, highlighting the rarity and severity of Mpg infections in cardiac disease (50).

Crohn’s Disease: A 44-year-old man with right-sided abdominal pain and non-bloody diarrhea was diagnosed with Crohn’s disease (CD) after a colonoscopy. During treatment, a TB test was positive, and a chest X-ray showed fibronodular changes. Although the sputum acid-fast smear was negative, cultures identified Mpg. The initial RIPE regimen was used but switched to isoniazid and rifampin due to side effects. Significant improvement in colitis was observed following mycobacterial treatment, suggesting a potential link between Mpg and CD (51).

Hemoptysis: A 54-year-old woman presented with hemoptysis and bilateral lung abnormalities, initially treated for community-acquired pneumonia. Initial respiratory cultures and acid-fast bacilli tests were negative, but later cultures identified Mpg. Despite initial improvement with azithromycin and ceftriaxone, the patient was lost to follow-up, leaving the long- term outcome unknown. This case highlights the need to consider slow-growing mycobacteria in persistent hemoptysis (52).

Lumbar Infection: A case of lumbar infection in a patient was attributed to Mpg, manifesting as persistent back pain. The diagnosis was confirmed through imaging and cultures. The patient responded well to a combination of antimicrobial therapy, including ethambutol and moxifloxacin, resulting in significant recovery. This case underscores the ability of Mpg to affect the musculoskeletal system and the importance of appropriate mycobacterial treatment (53).

Cervical Lymphadenitis: A rare case of infectious cervical lymphadenitis, in which both Citrobacter freundii, MAC, and Mpg were positive on core biopsy, has been reported. The patient received multiple antibiotics concurrently and was managed conservatively without surgical intervention. Symptoms resolved after 3 days of antimycobacterial treatment (clarithromycin), followed up for 3 months (54, 55).

Mpg has been associated with several clinical cases of infection. However, in most instances, a definitive causal relationship has not been clearly established. Rapid and accurate identification of Mpg infections is crucial, as patients show significant improvement when treated with anti-tuberculosis drugs and antibiotics. When conducting NTM culture tests, it is essential to consider the possibility of slow-growing mycobacteria. Therefore, cultures should be maintained for a duration of more than a month to ensure accurate detection. Given the stable prognosis of Mpg infections, precise detection is vital for establishing effective management and prevention strategies.

CONCLUSION

Mpg exhibits unique characteristics and versatility, making it a promising candidate for vaccine development, immunotherapy, and antibiotic screening. Its robust immunogenicity, potential as a recombinant vaccine vector, and efficacy in heterologous vaccination strategies highlight its potential for developing new and improved vaccines and therapies against various diseases. The environmental adaptability and clinical implications of Mpg underscore the need for ongoing research and surveillance to develop effective management and prevention strategies (Fig. 1). Further research and clinical trials are essential to fully realize the potential of Mpg in addressing some of the most pressing challenges in medicine and public health.

https://cdn.apub.kr/journalsite/sites/jbv/2024-054-04/N0290540402/images/JBV_2024_v54n4_273_f001.jpg
Fig. 1

Schematic representation showing the potential application and characteristics of Mpg.

References

1

Johansen MD, Herrmann JL, Kremer L. Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus. Nat Rev Microbiol. 2020;18(7):392-407.

10.1038/s41579-020-0331-132086501
2

Bhargava A, Bhargava M. Tuberculosis deaths are predictable and preventable: Comprehensive assessment and clinical care is the key. J Clin Tuberc Other Mycobact Dis. 2020;19:100155.

10.1016/j.jctube.2020.10015532211519PMC7082610
3

Bagcchi S. WHO's Global Tuberculosis Report 2022. Lancet Microbe. 2023;4(1):e20.

10.1016/S2666-5247(22)00359-736521512
4

Dailloux M, Abalain ML, Laurain C, Lebrun L, Loos-Ayav C, Lozniewski A, et al. Respiratory infections associated with nontuberculous mycobacteria in non-HIV patients. Eur Respir J. 2006;28(6):1211-1215.

10.1183/09031936.0006380617138678
5

Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med. 2012;185(8):881-886.

10.1164/rccm.201111-2016OC22312016PMC3360574
6

Harada K, Hagiya H, Funahashi T, Koyama T, Kano MR, Otsuka F. Trends in the Nontuberculous Mycobacterial Disease Mortality Rate in Japan: A Nationwide Observational Study, 1997-2016. Clin Infect Dis. 2021;73(2):e321-e326.

10.1093/cid/ciaa81032556251
7

Falkinham JO. 3rd. Environmental sources of nontuberculous mycobacteria. Clin Chest Med. 2015;36(1):35-41.

10.1016/j.ccm.2014.10.00325676517
8

Gopalaswamy R, Shanmugam S, Mondal R, Subbian S. Of tuberculosis and non-tuberculous mycobacterial infections - a comparative analysis of epidemiology, diagnosis and treatment. J Biomed Sci. 2020;27(1):74.

10.1186/s12929-020-00667-632552732PMC7297667
9

Kim BJ, Hong SH, Kook YH, Kim BJ. Mycobacterium paragordonae sp. nov., a slowly growing, scotochromogenic species closely related to Mycobacterium gordonae. Int J Syst Evol Microbiol. 2014;64(Pt 1):39-45.

10.1099/ijs.0.051540-024006480
10

Kim BJ, Kim BR, Kook YH, Kim BJ. A temperature sensitive Mycobacterium paragordonae induces enhanced protective immune responses against mycobacterial infections in the mouse model. Sci Rep. 2017;7(1):15230.

10.1038/s41598-017-15458-729123166PMC5680210
11

Kim BJ, Jeong H, Seo H, Lee MH, Shin HM, Kim BJ. Recombinant Mycobacterium paragordonae Expressing SARS-CoV-2 Receptor-Binding Domain as a Vaccine Candidate Against SARS-CoV-2 Infections. Front Immunol. 2021;12:712274.

10.3389/fimmu.2021.71227434512635PMC8432291
12

Kim BJ, Kim BR, Kook YH, Kim BJ. Potential of recombinant Mycobacterium paragordonae expressing HIV-1 Gag as a prime vaccine for HIV-1 infection. Sci Rep. 2019;9(1):15515.

10.1038/s41598-019-51875-631664100PMC6820866
13

Lee MH, Kim BR, Seo H, Oh J, Kim HL, Kim BJ. Live Mycobacterium paragordonae induces heterologous immunity of natural killer cells by eliciting type I interferons from dendritic cells via STING-dependent sensing of cyclic-di-GMP. Microbes Infect. 2023;25(7):105144.

10.1016/j.micinf.2023.10514437120009
14

Lee MH, Seo H, Lee MS, Kim BJ, Kim HL, Lee DH, et al. Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy. Front Immunol. 2023;14:1178688.

10.3389/fimmu.2023.117868837398665PMC10312308
15

Ziogas A, Netea MG. Trained immunity-related vaccines: innate immune memory and heterologous protection against infections. Trends Mol Med. 2022;28(6):497-512.

10.1016/j.molmed.2022.03.00935466062
16

Kim BJ, Cha GY, Kim BR, Kook YH, Kim BJ. Insights From the Genome Sequence of Mycobacterium paragordonae, a Potential Novel Live Vaccine for Preventing Mycobacterial Infections: The Putative Role of Type VII Secretion Systems for an Intracellular Lifestyle Within Free-Living Environmental Predators. Front Microbiol. 2019;10:1524.

10.3389/fmicb.2019.0152431333625PMC6616192
17

Pereira SG, Alarico S, Tiago I, Reis D, Nunes-Costa D, Cardoso O, et al. Studies of antimicrobial resistance in rare mycobacteria from a nosocomial environment. BMC Microbiol. 2019;19(1):62.

10.1186/s12866-019-1428-430890149PMC6425705
18

Moradi S, Nasiri MJ, Pourahmad F, Darban-Sarokhalil D. Molecular characterization of nontuberculous mycobacteria in hospital waters: a two-year surveillance study in Tehran, Iran. J Water Health. 2019;17(2):350-356.

10.2166/wh.2019.29430942784
19

Takajo I, Iwao C, Aratake M, Nakayama Y, Yamada A, Takeda N, et al. Pseudo-outbreak of Mycobacterium paragordonae in a hospital: possible role of the aerator/rectifier connected to the faucet of the water supply system. J Hosp Infect. 2020;104(4):545-551.

10.1016/j.jhin.2019.11.01431785317
20

Arfaatabar M, Karami P, Khaledi A. An update on prevalence of slow-growing mycobacteria and rapid-growing mycobacteria retrieved from hospital water sources in Iran - a systematic review. Germs. 2021;11(1):97-104.

10.18683/germs.2021.124533898346PMC8057855
21

Cheung CY, Cheng NHY, Ting WM, Chak WL. Mycobacterium paragordonae: a rare cause of peritonitis in a peritoneal dialysis patient. Clin Nephrol. 2017;88(12):371-372.

10.5414/CN10927229057736
22

Kaelin MB, Kuster SP, Hasse B, Schulthess B, Imkamp F, Halbe M, et al. Diversity of nontuberculous mycobacteria in Heater-Cooler Devices - results from prospective surveillance. J Hosp Infect. 2020:S0195-6701(20)30105-5.

23

Li Y, Zhang W, Zhao J, Lai W, Zhao Y, Li Y, et al. Mycobacterium paragordonae is an emerging pathogen in human pulmonary disease: clinical features, antimicrobial susceptibility testing and outcomes. Emerg Microbes Infect. 2022;11(1):1973-1981.

10.1080/22221751.2022.210345335916253PMC9364734
24

Azadi D, Shojaei H, Pourchangiz M, Dibaj R, Davarpanah M, Naser AD. Species diversity and molecular characterization of nontuberculous mycobacteria in hospital water system of a developing country, Iran. Microb Pathog. 2016;100:62-69.

10.1016/j.micpath.2016.09.00427616445
25

Cohn ML, Waggoner RF, McClatchy JK. The 7H11 medium for the cultivation of mycobacteria. Am Rev Respir Dis. 1968;98(2):295-296.

26

Hines N, Payeur JB, Hoffman LJ. Comparison of the recovery of Mycobacterium bovis isolates using the BACTEC MGIT 960 system, BACTEC 460 system, and Middlebrook 7H10 and 7H11 solid media. J Vet Diagn Invest. 2006;18(3):243-250.

10.1177/10406387060180030216789711
27

Bespyatykh JA, Manicheva OA, Smolyakov AV, Dogonadze MZ, Zhuravlev VY, Shitikov EA, et al. Influence of cultivation conditions on the proteomic profile of Mycobacterium tuberculosis H37RV. Biomed Khim. 2017;63(4):334-340.

10.18097/PBMC2017630433428862605
28

Cha GY, Seo H, Oh J, Kim BJ, Kim BJ. Potential Use of Mycobacterium paragordonae for Antimycobacterial Drug Screening Systems. J Microbiol. 2023;61(1):121-129.

10.1007/s12275-022-00009-136719620
29

Pym AS, Brodin P, Majlessi L, Brosch R, Demangel C, Williams A, et al. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nat Med. 2003;9(5):533-539.

10.1038/nm85912692540
30

Pooransingh S, Sakhamuri S. Need for BCG Vaccination to Prevent TB in High-Incidence Countries and Populations. Emerg Infect Dis. 2020;26(3):624-625.

10.3201/eid2603.19123231922950PMC7045831
31

Stoitzner P, Tripp CH, Douillard P, Saeland S, Romani N. Migratory Langerhans cells in mouse lymph nodes in steady state and inflammation. J Invest Dermatol. 2005;125(1):116-125.

10.1111/j.0022-202X.2005.23757.x15982311
32

Kissenpfennig A, Henri S, Dubois B, Laplace-Builhé C, Perrin P, Romani N, et al. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity. 2005;22(5):643-654.

10.1016/j.immuni.2005.04.00415894281
33

Han SJ, Song T, Cho YJ, Kim JS, Choi SY, Bang HE, et al. Complete genome sequence of Mycobacterium tuberculosis K from a Korean high school outbreak, belonging to the Beijing family. Stand Genomic Sci. 2015;10:78.

10.1186/s40793-015-0071-426473025PMC4606834
34

Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012;109(43):17537-17542.

10.1073/pnas.120287010922988082PMC3491454
35

Tarancón R, Domínguez-Andrés J, Uranga S, Ferreira AV, Groh LA, Domenech M, et al. New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia. PLoS Pathog. 2020;16(4):e1008404.

10.1371/journal.ppat.100840432240273PMC7117655
36

Mata E, Tarancon R, Guerrero C, Moreo E, Moreau F, Uranga S, et al. Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis. Sci Immunol. 2021;6(63):eabc2934.

10.1126/sciimmunol.abc293434559551
37

Leentjens J, Kox M, Stokman R, Gerretsen J, Diavatopoulos DA, van Crevel R, et al. BCG Vaccination Enhances the Immunogenicity of Subsequent Influenza Vaccination in Healthy Volunteers: A Randomized, Placebo-Controlled Pilot Study. J Infect Dis. 2015;212(12):1930-1938.

10.1093/infdis/jiv33226071565
38

Mukherjee S, Subramaniam R, Chen H, Smith A, Keshava S, Shams H. Boosting efferocytosis in alveolar space using BCG vaccine to protect host against influenza pneumonia. PLoS One. 2017;12(7):e0180143.

10.1371/journal.pone.018014328686604PMC5501455
39

Spencer JC, Ganguly R, Waldman RH. Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Guérin. J Infect Dis. 1977;136(2):171-175.

10.1093/infdis/136.2.171894076
40

Arts RJW, Moorlag S, Novakovic B, Li Y, Wang SY, Oosting M, et al. BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host Microbe. 2018;23(1):89-100.e5.

10.1016/j.chom.2017.12.01029324233
41

Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B, Hyodo M, et al. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 2011;478(7370):515-518.

10.1038/nature1042921947006PMC3203314
42

Chang WL, Barry PA, Szubin R, Wang D, Baumgarth N. Human cytomegalovirus suppresses type I interferon secretion by plasmacytoid dendritic cells through its interleukin 10 homolog. Virology. 2009;390(2):330-337.

10.1016/j.virol.2009.05.01319524994PMC2747589
43

Madera S, Rapp M, Firth MA, Beilke JN, Lanier LL, Sun JC. Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide. J Exp Med. 2016;213(2):225-233.

10.1084/jem.2015071226755706PMC4749923
44

Lee SY, Yang SB, Choi YM, Oh SJ, Kim BJ, Kook YH, et al. Heat-killed Mycobacterium paragordonae therapy exerts an anti-cancer immune response via enhanced immune cell mediated oncolytic activity in xenograft mice model. Cancer Lett. 2020;472:142-150.

10.1016/j.canlet.2019.12.02831874244
45

Azadi D, Shojaei H, Mobasherizadeh S, Naser AD. Screening, isolation and molecular identification of biodegrading mycobacteria from Iranian ecosystems and analysis of their biodegradation activity. AMB Express. 2017;7(1):180.

10.1186/s13568-017-0472-428933031PMC5607059
46

Rivera-Calzada A, Famelis N, Llorca O, Geibel S. Type VII secretion systems: structure, functions and transport models. Nat Rev Microbiol. 2021;19(9):567-584.

10.1038/s41579-021-00560-534040228
47

Shen Y, Haig SJ, Prussin AJ, 2nd, LiPuma JJ, Marr LC, Raskin L. Shower water contributes viable nontuberculous mycobacteria to indoor air. PNAS Nexus. 2022;1(5):pgac145.

10.1093/pnasnexus/pgac14536712351PMC9802317
48

Maleki MR, Kafil HS, Harzandi N, Moaddab SR. Identification of nontuberculous mycobacteria isolated from hospital water by sequence analysis of the hsp65 and 16S rRNA genes. J Water Health. 2017;15(5):766-774.

10.2166/wh.2017.04629040079
49

Machida Y, Tang BCC, Yamada M, Sato S, Nakajima K, Matoyama H, et al. Mycobacteriosis in cultured koi carp Cyprinus carpio caused by Mycobacterium paragordonae and two Mycolicibacterium spp. Aquaculture. 2021;539:736656.

10.1016/j.aquaculture.2021.736656
50

Jinah R, Ryan T, Sibbald M. A Case of Pericarditis and Pericardial Masses Associated With Mycobacterium paragordonae. Clin Med Insights Cardiol. 2023;17:11795468231189039.

10.1177/1179546823118903937637260PMC10460162
51

Zou Y, Wu YC, Korman A. S2714 Case Report: Mycobacterium paragordonae Associated Crohn's Disease. The American Journal of Gastroenterology. 2022;117(10S):e1787.

10.14309/01.ajg.0000867496.96241.cb
52

Karim A, Fnu Z. MYCOBACTERIUM PARAGORDONEA: A CAUSE OF HEMOPTYSIS? Monday Medical Student/Resident Case Report Posters. 2019;156(4).

10.1016/j.chest.2019.08.729
53

Tan YZ, Yuan T, Tan L, Tian YQ, Long YZ. Lumbar infection caused by Mycobacterium paragordonae: A case report. World J Clin Cases. 2021;9(29):8879-8887.

10.12998/wjcc.v9.i29.887934734070PMC8546838
54

Singh D, Sit S, Singh N. Diagnostic and therapeutic dilemma of cervical adenitis in an adult. BMJ Case Reports. 2022;15(9):e247303.

10.1136/bcr-2021-247303PMC9462124
55

2022 Annual Conference Conférence Annuelle. J Assoc Med Microbiol Infect Dis Can. 2022;7(s1):1-131.

10.3138/jammi.7.s1.abst
페이지 상단으로 이동하기