Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficie...Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.展开更多
Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are co...Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are considered as natural reservoir of M. bovis. However, in Burkina Faso, the circulation of these strains remains poorly understood and documented. This study aimed to identify and characterize Mycobacterium strains from suspected carcasses during routine meat inspection at Bobo-Dioulasso refrigerated slaughterhouse. A prospective cross-sectional study was conducted from January 2021 to December 2022 on cases of seizures linked to suspected bovine tuberculosis. Microbiological and molecular analyzes were used for mycobacterial strain isolation and characterization. Out of 50 samples, 24% tested positive by microscopy and 12% by culture. Molecular analysis identified 6 strains of Mycobacteria, exclusively Mycobacterium bovis specifically the subspecies bovis (Mycobacterium bovis subsp bovis). In conclusion, M. bovis subsp bovis is the primary agent responsible for bovine tuberculosis in Bobo-Dioulasso. Continuous monitoring of mycobacterial strains is therefore necessary for the effective control of this pathology in the local cattle population.展开更多
The incidence of Mycobacterium avium complex pulmonary disease (MACPD) has been globally increasing. The present study aims to provide a comprehensive analysis of clinical characteristics and treatment response among ...The incidence of Mycobacterium avium complex pulmonary disease (MACPD) has been globally increasing. The present study aims to provide a comprehensive analysis of clinical characteristics and treatment response among patients in the Amazon region of Brazil and conduct a retrospective cohort study at a prominent referral hospital in the State of Par, Brazil, from 2012 to 2020. The M. avium group represented 58.9% of cases, followed by M. intracellulare (35.7%), M. colombiense (3.6%), and M. chimaera (1.8%). The majority of patients (73.2%) were female and with an average age of 63 years. Primary clinical manifestations included persistent cough and sputum production. The Charlson comorbidity index (CCI) averaged 2.47, with 36.3% of patients having a CCI score equal to higher than 3. Notably, over 70% of patients had received treatment for pulmonary tuberculosis before initiating treatment for MAC infection. The fibrocavitary radiologic form was the most prevalent (55.4%), frequently exhibiting a bilateral distribution (53.6%). Antimicrobial susceptibility revealed a significant prevalence of MAC resistance to drugs in the therapeutic regimen. Despite this, most of the patients experienced clinical improvement (50%). In conclusion, this study highlights a higher prevalence of MAC infections among middle-aged women, with a history of pulmonary tuberculosis treatment and presenting the fibrocavitary radiological form was predominant.展开更多
Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of th...Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.展开更多
Tuberculosis (TB) is a serious infectious disease and its control is considered a challenge, particularly among vulnerable populations such as prisoners. The prevalence of TB in prisons is an alarming public health pr...Tuberculosis (TB) is a serious infectious disease and its control is considered a challenge, particularly among vulnerable populations such as prisoners. The prevalence of TB in prisons is an alarming public health problem in many countries. The aim of this study is to describe the epidemiology of tuberculosis and the strategies for controlling this disease in the Chadian prison population. During the course of our study, the prevalence of tuberculosis in prisons was 9.64%. The age group between 55 years and over (43.33%) was the most represented in this study, and all patients were men with a frequency of 62.66%. The cross-tabulation of Culture_7H9G and Culture_7H9P showed that out of our total positive sample, we found a total of 87 positive strains and 63 negative strains. Our study shows that it is essential to know the prevalence of tuberculosis in all the country’s prisons. Indeed, this can serve as an indication of the need for action in prisons to reduce TB rates, in particular by improving the structure of prison environments, diagnosing new cases quickly and accurately, identifying drug-resistant strains and implementing effective, direct treatment observed in people with tuberculosis.展开更多
Background: Tuberculous endocarditis is a rare but serious complication of heart valve replacement surgery. We report the case of a 24-year-old patient, who presented with tuberculous endocarditis after mechanical mit...Background: Tuberculous endocarditis is a rare but serious complication of heart valve replacement surgery. We report the case of a 24-year-old patient, who presented with tuberculous endocarditis after mechanical mitral valve replacement, with a favorable clinical course following anti-tuberculosis treatment. Case Presentation: We report a 24-year-old male patient, admitted to the cardiac surgery department of the Fann Hospital (Dakar, Senegal), for the management of severe mixed (rheumatic and endocarditic) mitral insufficiency with associated tricuspid insufficiency. He had a history of recurrent angina and polyarthralgia in childhood, was hospitalized several times for refractory global cardiac decompensation, and for a suspected infective endocarditis a month before his admission. On admission, the clinical examination revealed signs suggestive of mitral and tricuspid insufficiency. Transthoracic echocardiography revealed severe post-endocarditic mitral insufficiency with A3 amputation, highly mobile 15 mm vegetations on the free edge of the large valve, moderate tricuspid insufficiency, and severe pulmonary artery hypertension. Mechanical mitral valve replacement and tricuspid valve annuloplasty using autologous pericardial strip were performed via median sternotomy. After ten days, the patient presented with global cardiac decompensation associated with a clinico-biological infectious syndrome, and tans-oesophageal echography revealed an abscess at the sinotubular junction, communicating with the aorta. A thoraco-abdomino-pelvic CT scan was done, which revealed a bilateral alveolar-interstitial syndrome with mediastinal lymphadenopathy. Anti-tuberculosis treatment with RHZE was initiated for 06 months. The clinical course was favorable. Conclusion: Tuberculous endocarditis in prostheses is a serious complication of heart valve replacement surgery, which may evolve favorably under medical treatment.展开更多
BACKGROUND Owing to the advancement in bacterial identification techniques,the detection rate of non-tuberculous mycobacterium(NTM)has been on the rise.Different from Mycobacterium tuberculosis,the clinical symptoms o...BACKGROUND Owing to the advancement in bacterial identification techniques,the detection rate of non-tuberculous mycobacterium(NTM)has been on the rise.Different from Mycobacterium tuberculosis,the clinical symptoms of NTM are not easily detected,and the clinical efficacy and prognosis are somewhat heterogeneous.To report a case of Mycobacterium gordoniasis of cervical lymph node diagnosed in Anhui Chest Hospital in July 2022.CASE SUMMARY Upon examination,the patient who weighed 67.5 kg,was human immunodeficiency virus negative,healthy,without hypertension,diabetes,heart disease and other basic diseases microscopic analysis revealed granulomatous inflammation with coagulation necrosis in the lymphocyte,and tuberculosis was not ruled out.Plain computed tomography scans of the neck and chest indicated the presence of a single grayish-yellow and grayish-brown tissue,the dimensions of which was top of form 10.5 cm×3.0 cm×1.5 cm.After pathological consultation in our hospital,the diagnosis was confirmed as NTM infection.CONCLUSION This case report and the clinical epidemiological research on improving NTM have important guiding significance for improving decision-making in clinical treatments.展开更多
BACKGROUND Mycobacterium houstonense(M.houstonense)belongs to the nontuberculous mycobacterium group.Infection caused by M.houstonense is prone to recurrence.CASE SUMMARY We present a patient who was diagnosed with os...BACKGROUND Mycobacterium houstonense(M.houstonense)belongs to the nontuberculous mycobacterium group.Infection caused by M.houstonense is prone to recurrence.CASE SUMMARY We present a patient who was diagnosed with osteomyelitis caused by M.houstonense and treated with a combination of cefoxitin,and amikacin combined with linezolid.CONCLUSION The emergence of metagenomic next-generation sequencing(NGS)has brought new hope for the diagnosis and treatment of listeria meningitis.NGS can analyze a large number of nucleic acid sequences in a short time and quickly determine the pathogen species in the sample.Compared with traditional cerebrospinal fluid culture,NGS can greatly shorten the diagnosis time and provide strong support for the timely treatment of patients.Regarding treatment,NGS can also play an important role.Rapid and accurate diagnosis can enable patients to start targeted treatment as soon as possible and improve the treatment effect.At the same time,by monitoring the changes in pathogen resistance,the treatment plan can be adjusted in time to avoid treatment failure.展开更多
Background: Mycobacterium avium complex (MAC) infection case which involves bones and joints are rare scenarios. Here, we report a rare case of Penicillium marneffei (PM), lung infection and systemic multi joint damag...Background: Mycobacterium avium complex (MAC) infection case which involves bones and joints are rare scenarios. Here, we report a rare case of Penicillium marneffei (PM), lung infection and systemic multi joint damage reported with positive anti-interferon-gamma at the same time. Case Presentation: A 55-year-old woman with fever for 10 days due to repeated multiple joint pain for more than one month was admitted to our hospital on September 19th 2020. During hospitalization, the patient was confirmed with mycobacterium avium combined with Penicillium marneffei (PM) infection involving multiple bone joints. Antifungal therapy and immunity regulatory agent were given during hospitalization. Following pharmocol-therapy, symptoms gradually improved, and the patient was discharged. Conclusions: The patient was considered disseminated and refractory non-tubercular mycobacterium (NTM) combined with Penicillium marneffei infection. In addition, we found that anti IFN-γ autoantibodies are closely related. Although the current incidence of this patient is related to anti IFN-γ, there is a strong correlation between autoantibody-mediated immunodeficiency in adults.展开更多
BACKGROUND Infections by non-tuberculous mycobacteria(NTM)have become more common in recent years.Mycobacterium canariasense(M.canariasense)was first reported as an opportunistic pathogen in 2004,but there have been v...BACKGROUND Infections by non-tuberculous mycobacteria(NTM)have become more common in recent years.Mycobacterium canariasense(M.canariasense)was first reported as an opportunistic pathogen in 2004,but there have been very few case reports since then.Nocardia is a genus of aerobic and Gram-positive bacilli,and these species are also opportunistic pathogens and in the Mycobacteriales order.Conventional methods for diagnosis of NTM are inefficient.Metagenomic next-generation sequencing(mNGS)can rapidly detect many pathogenic microorganisms,even rare species.Most NTM and Nocardia infections occur in immunocompromised patients with atypical clinical symptoms.There are no previous reports of infection by M.canariasense and Nocardia farcinica(N.farcinica),especially in immunocompetent patients.This case report describes an immunocompetent 52-year-old woman who had overlapping infections of M.canariasense,N.farcinica,and Candida parapsilosis(C.parapsilosis)based on mNGS.CASE SUMMARY A 52-year-old woman presented with a productive cough and chest pain for 2 wk,and recurrent episodes of moderate-grade fever for 1 wk.She received antibiotics for 1 wk at a local hospital,and experienced defervescence,but the productive cough and chest pain persisted.We collected samples of a lung lesion and alveolar lavage fluid for mNGS.The lung tissue was positive for M.canariasense,N.farcinica,and C.parapsilosis,and the alveolar lavage fluid was positive for M.canariasense.The diagnosis was pneumonia,and application of appropriate antibiotic therapy cured the patient.CONCLUSION Etiological diagnosis is critical for patients with infectious diseases.mNGS can identify rare and novel pathogens,and does not require a priori knowledge.展开更多
Objective:To analyze the mutation characteristics of inhA and katG genes in isoniazid-resistant Mycobacterium tuberculosis in Xinjiang.Methods:The katG and inhA in 148 strains of isoniazid-resistant Mycobacterium tube...Objective:To analyze the mutation characteristics of inhA and katG genes in isoniazid-resistant Mycobacterium tuberculosis in Xinjiang.Methods:The katG and inhA in 148 strains of isoniazid-resistant Mycobacterium tuberculosis were amplified through fluorescence quantitative PCR,and the amplified products were sequenced and compared.Results:The inhA gene mutation rate of 148 strains of isoniazid-resistant mycobacterium tuberculosis was 13.51%(20/148),among which the inhA gene mutation rate among patients of Han,Uygur,and Kazakh ethnicity were 15.87%,13.21%,and 17.65%,respectively.There was no significant difference in the inhA mutation rate among nationalities(c^(2)=2.897,P>0.05).The mutation rate of the katG gene was 84.46%(125/148),among which the mutation rates of patients of Han,Uyghur,and Kazak ethnicities were 82.54%,84.91%,and 76.47%,respectively.The Hui and other ethnic groups were all affected by the katG gene mutation.There was no significant difference in the mutation rate of the katG gene among different ethnicities(c^(2)=3.772,P>0.05).The mutation rates of the inhA gene in southern Xinjiang,northern Xinjiang,and other provinces were 18.60%,9.28%,and 37.50%,respectively.The mutation rates of the inhA gene in different regions were statistically different(c^(2)=6.381,P<0.05).There was no significant difference in the inhA mutation rate between patients from southern and northern Xinjiang(c^(2)=2.214,P>0.05)and between southern Xinjiang and other provinces(c^(2)=1.424,P>0.05).However,the mutation rate of the inhA gene in patients from other provinces was higher than that in northern Xinjiang(c^(2)=5.539,P<0.05).The mutation rates of the katG gene in southern Xinjiang,northern Xinjiang,and other provinces were 81.40%,87.63%,and 62.50%,respectively.There was no significant difference in the mutation rates of the katG gene among different regions(c^(2)=3.989,P>0.05).Conclusion:katG gene mutation was predominant in isoniazid-resistant tuberculosis patients in Xinjiang Uygur Autonomous Region,and inhA and katG gene mutation were no different among different ethnic groups.展开更多
Objective To identify the novel species ‘Mycobacterium fukienense' sp. nov of Mycobacterium chelonoe/abscessus complex from tuberculosis patients in Fujian Province, China. Methods Five of 27 clinical Mycobucterium ...Objective To identify the novel species ‘Mycobacterium fukienense' sp. nov of Mycobacterium chelonoe/abscessus complex from tuberculosis patients in Fujian Province, China. Methods Five of 27 clinical Mycobucterium isolates (CIs) were previously identified as M. chelonoe/obscessus complex by sequencing the hsp65, rpoB, 165-235 rRNA internal transcribed spacer region (its), recA and sodA house-keeping genes commonly used to describe the molecular characteristics of Mycobocterium. Clinical Mycobecterium isolates were classified according to the gene sequence using a clustering analysis program. Sequence similarity within clusters and diversity between clusters were analyzed. Results The 5 isolates were identified with distinct sequences exhibiting 99.8% homology in the hsp65 gene. However, a complete lack of homology was observed among the sequences of the rpoB, 165-235 rRNA internal tronscribed spacer region (its), sodA, and recA genes as compared with the M. obscessus. Furthermore, no match for rpoB, sodA, and recA genes was identified among the published sequences. Conclusion The novel species, Mycobacterium fukienense, is identified from tuberculosis patients in Fujian Province, China, which does not belong to any existing subspecies of M. cheloneo/abscessus complex.展开更多
Resuscitation promoting factor E (RpfE) is one of the five Rpf-like proteins in Mycobacterium tuberculos& (M. tuberculosis). These Rpf-like proteins are secretory, which make them candidates for recognition by th...Resuscitation promoting factor E (RpfE) is one of the five Rpf-like proteins in Mycobacterium tuberculos& (M. tuberculosis). These Rpf-like proteins are secretory, which make them candidates for recognition by the host immune system. In this study, the RpfE gene was amplified from M. tuberculosis, cloned into the expression vectors pDE22 and pPRO EXHT, and were expressed in Mycobacterium vaccae (M. vaccae) and Escherichia coli DHSa, respec- tively. Both recombinant RpfE proteins were purified by Ni-Sepharose affinity chromatography, and were given to C57BL/6 mice. The RpfE proteins elicited T cell proliferation, and stimulated the production of gamma interferon (IFN-y), interleukin-10 (IL-10) and IL-12. Our results indicated that the RpfE protein expressed in M. vaccae could more efficiently stimulate cellular immune response, making it a promising candidate as a subunit vaccine.展开更多
Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were al...Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study. Methods Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay. Results Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacteriurn elephantis (M. elephantis). The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. Conclusion To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China.展开更多
Mycobacterium paragordonae(M.paragordonae),a slow-growing,acid-resistant mycobacterial species,was first isolated from the sputum of a lung infection patient in South Korea in 2014.Infections caused by M.paragordonae ...Mycobacterium paragordonae(M.paragordonae),a slow-growing,acid-resistant mycobacterial species,was first isolated from the sputum of a lung infection patient in South Korea in 2014.Infections caused by M.paragordonae are rare.CASE SUMMARY Herein,we report the case of a 53-year-old patient who presented with fever and low back pain.Lumbar nuclear magnetic resonance imaging revealed the destruction of the lumbar vertebra with peripheral abscess formation.After antiinfective and diagnostic anti-tuberculosis treatment,the patient had no further fever,but the back pain was not relieved.Postoperatively,the necrotic material was sent for pathological examination,and all tests related to tuberculosis were negative,but pus culture suggested nontuberculous mycobacteria.The necrotic tissue specimens were subjected to metagenomic next-generation sequencing,which indicated the presence of M.paragordonae.Finally,the infecting pathogen was identified,and the treatment plan was adjusted.The patient was in good condition during the follow-up period.CONCLUSION M.paragordonae,a rare nontuberculous mycobacterium,can also cause spinal infections.In the clinic,it is necessary to identify nontuberculous mycobacteria for spinal infections similar to Mycobacterium tuberculosis.展开更多
The serine proteases of Mycobacteria tuberculosis(Mtb)are important contributors to the process of bacterial invasion and its pathogenesis.In the present study,we systematically characterized the role of the Rv1043c p...The serine proteases of Mycobacteria tuberculosis(Mtb)are important contributors to the process of bacterial invasion and its pathogenesis.In the present study,we systematically characterized the role of the Rv1043c protein in Mycobacterium infection by purifying the Rv1043c protein in Escherichia coli and constructing a Mycobacterium smegmatis(Msg)strain overexpressing Rv1043c(Msg_Rv1043c).We found that Rv1043c had serine protease activity and localized to the surface of Mtb.We determined that the optimal pH and temperature for the Rv1043c serine protease were 9.0 and 45°C,respectively.Moreover,the serine protease activity of Rv1043c was enhanced by divalent metal ions of Ca^(2+)and Mg^(2+).Site-directed mutagenesis studies demonstrated that the serine 279 residue in Rv1043c plays a catalytic role.Additionally,mouse model studies confirmed that Rv1043c significantly enhanced the survival of Msg in vivo,induced pulmonary injury and lung cell apoptosis,and promoted the release of pro-inflammatory cytokines interleukin-1βand interleukin-6 in mice.This study presents novel insights into the relationship between mycobacterial serine protease and the pathogenesis of the disease.展开更多
BACKGROUND The incidence of infection with Mycobacterium abscessus(M.abscessus)has increased in recent years.This increase is partly associated with invasive cosmetic procedures.CASE SUMMARY The purpose of this case s...BACKGROUND The incidence of infection with Mycobacterium abscessus(M.abscessus)has increased in recent years.This increase is partly associated with invasive cosmetic procedures.CASE SUMMARY The purpose of this case summary is to increase clinicians'awareness of M.abscessus infection and reduce mycobacterial infection caused by cosmetic procedures.We report the case of a 45-year-old woman who received acetyl hexapeptide-8(argireline)injections in the forehead and temples,and erythema,nodules,and abscesses appeared at the injection sites after one week.The pus specimens were examined by microbiological culture and confirmed to be positive for M.abscessus.Clarithromycin 500 mg twice daily and moxifloxacin 400 mg once daily were administered for 5 mo and the lesions gradually subsided.CONCLUSION We report here for the first time a case of infection with M.abscessus after argireline injection.This condition is easily misdiagnosed as a common bacterial infection.Microbiological examinations are helpful for diagnosis and standardized cosmetic procedures can prevent infection with M.abscessus.展开更多
基金supported by grants from the Natural Science Foundation of Huai'an Science and Technology Bureau(Grant No.HAB202312)the Science and Technology Development Fund of the Affiliated Hospital of Xuzhou Medical University(Grant No.XYFY2021018).
文摘Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.
文摘Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are considered as natural reservoir of M. bovis. However, in Burkina Faso, the circulation of these strains remains poorly understood and documented. This study aimed to identify and characterize Mycobacterium strains from suspected carcasses during routine meat inspection at Bobo-Dioulasso refrigerated slaughterhouse. A prospective cross-sectional study was conducted from January 2021 to December 2022 on cases of seizures linked to suspected bovine tuberculosis. Microbiological and molecular analyzes were used for mycobacterial strain isolation and characterization. Out of 50 samples, 24% tested positive by microscopy and 12% by culture. Molecular analysis identified 6 strains of Mycobacteria, exclusively Mycobacterium bovis specifically the subspecies bovis (Mycobacterium bovis subsp bovis). In conclusion, M. bovis subsp bovis is the primary agent responsible for bovine tuberculosis in Bobo-Dioulasso. Continuous monitoring of mycobacterial strains is therefore necessary for the effective control of this pathology in the local cattle population.
文摘The incidence of Mycobacterium avium complex pulmonary disease (MACPD) has been globally increasing. The present study aims to provide a comprehensive analysis of clinical characteristics and treatment response among patients in the Amazon region of Brazil and conduct a retrospective cohort study at a prominent referral hospital in the State of Par, Brazil, from 2012 to 2020. The M. avium group represented 58.9% of cases, followed by M. intracellulare (35.7%), M. colombiense (3.6%), and M. chimaera (1.8%). The majority of patients (73.2%) were female and with an average age of 63 years. Primary clinical manifestations included persistent cough and sputum production. The Charlson comorbidity index (CCI) averaged 2.47, with 36.3% of patients having a CCI score equal to higher than 3. Notably, over 70% of patients had received treatment for pulmonary tuberculosis before initiating treatment for MAC infection. The fibrocavitary radiologic form was the most prevalent (55.4%), frequently exhibiting a bilateral distribution (53.6%). Antimicrobial susceptibility revealed a significant prevalence of MAC resistance to drugs in the therapeutic regimen. Despite this, most of the patients experienced clinical improvement (50%). In conclusion, this study highlights a higher prevalence of MAC infections among middle-aged women, with a history of pulmonary tuberculosis treatment and presenting the fibrocavitary radiological form was predominant.
基金funded by the National Key R&D Program of China [2022YFC2305200]Natural Science Foundation of Xinjiang Uygur Autonomous Region [2021A01D145 and 2022D01A115]Applied Technology Research and Development Programing Project of Kashgar Prefecture [KS2021031 and KS2021034]。
文摘Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
文摘Tuberculosis (TB) is a serious infectious disease and its control is considered a challenge, particularly among vulnerable populations such as prisoners. The prevalence of TB in prisons is an alarming public health problem in many countries. The aim of this study is to describe the epidemiology of tuberculosis and the strategies for controlling this disease in the Chadian prison population. During the course of our study, the prevalence of tuberculosis in prisons was 9.64%. The age group between 55 years and over (43.33%) was the most represented in this study, and all patients were men with a frequency of 62.66%. The cross-tabulation of Culture_7H9G and Culture_7H9P showed that out of our total positive sample, we found a total of 87 positive strains and 63 negative strains. Our study shows that it is essential to know the prevalence of tuberculosis in all the country’s prisons. Indeed, this can serve as an indication of the need for action in prisons to reduce TB rates, in particular by improving the structure of prison environments, diagnosing new cases quickly and accurately, identifying drug-resistant strains and implementing effective, direct treatment observed in people with tuberculosis.
文摘Background: Tuberculous endocarditis is a rare but serious complication of heart valve replacement surgery. We report the case of a 24-year-old patient, who presented with tuberculous endocarditis after mechanical mitral valve replacement, with a favorable clinical course following anti-tuberculosis treatment. Case Presentation: We report a 24-year-old male patient, admitted to the cardiac surgery department of the Fann Hospital (Dakar, Senegal), for the management of severe mixed (rheumatic and endocarditic) mitral insufficiency with associated tricuspid insufficiency. He had a history of recurrent angina and polyarthralgia in childhood, was hospitalized several times for refractory global cardiac decompensation, and for a suspected infective endocarditis a month before his admission. On admission, the clinical examination revealed signs suggestive of mitral and tricuspid insufficiency. Transthoracic echocardiography revealed severe post-endocarditic mitral insufficiency with A3 amputation, highly mobile 15 mm vegetations on the free edge of the large valve, moderate tricuspid insufficiency, and severe pulmonary artery hypertension. Mechanical mitral valve replacement and tricuspid valve annuloplasty using autologous pericardial strip were performed via median sternotomy. After ten days, the patient presented with global cardiac decompensation associated with a clinico-biological infectious syndrome, and tans-oesophageal echography revealed an abscess at the sinotubular junction, communicating with the aorta. A thoraco-abdomino-pelvic CT scan was done, which revealed a bilateral alveolar-interstitial syndrome with mediastinal lymphadenopathy. Anti-tuberculosis treatment with RHZE was initiated for 06 months. The clinical course was favorable. Conclusion: Tuberculous endocarditis in prostheses is a serious complication of heart valve replacement surgery, which may evolve favorably under medical treatment.
文摘BACKGROUND Owing to the advancement in bacterial identification techniques,the detection rate of non-tuberculous mycobacterium(NTM)has been on the rise.Different from Mycobacterium tuberculosis,the clinical symptoms of NTM are not easily detected,and the clinical efficacy and prognosis are somewhat heterogeneous.To report a case of Mycobacterium gordoniasis of cervical lymph node diagnosed in Anhui Chest Hospital in July 2022.CASE SUMMARY Upon examination,the patient who weighed 67.5 kg,was human immunodeficiency virus negative,healthy,without hypertension,diabetes,heart disease and other basic diseases microscopic analysis revealed granulomatous inflammation with coagulation necrosis in the lymphocyte,and tuberculosis was not ruled out.Plain computed tomography scans of the neck and chest indicated the presence of a single grayish-yellow and grayish-brown tissue,the dimensions of which was top of form 10.5 cm×3.0 cm×1.5 cm.After pathological consultation in our hospital,the diagnosis was confirmed as NTM infection.CONCLUSION This case report and the clinical epidemiological research on improving NTM have important guiding significance for improving decision-making in clinical treatments.
基金Supported by The National Natural Science Foundation of China,No.82100631.
文摘BACKGROUND Mycobacterium houstonense(M.houstonense)belongs to the nontuberculous mycobacterium group.Infection caused by M.houstonense is prone to recurrence.CASE SUMMARY We present a patient who was diagnosed with osteomyelitis caused by M.houstonense and treated with a combination of cefoxitin,and amikacin combined with linezolid.CONCLUSION The emergence of metagenomic next-generation sequencing(NGS)has brought new hope for the diagnosis and treatment of listeria meningitis.NGS can analyze a large number of nucleic acid sequences in a short time and quickly determine the pathogen species in the sample.Compared with traditional cerebrospinal fluid culture,NGS can greatly shorten the diagnosis time and provide strong support for the timely treatment of patients.Regarding treatment,NGS can also play an important role.Rapid and accurate diagnosis can enable patients to start targeted treatment as soon as possible and improve the treatment effect.At the same time,by monitoring the changes in pathogen resistance,the treatment plan can be adjusted in time to avoid treatment failure.
文摘Background: Mycobacterium avium complex (MAC) infection case which involves bones and joints are rare scenarios. Here, we report a rare case of Penicillium marneffei (PM), lung infection and systemic multi joint damage reported with positive anti-interferon-gamma at the same time. Case Presentation: A 55-year-old woman with fever for 10 days due to repeated multiple joint pain for more than one month was admitted to our hospital on September 19th 2020. During hospitalization, the patient was confirmed with mycobacterium avium combined with Penicillium marneffei (PM) infection involving multiple bone joints. Antifungal therapy and immunity regulatory agent were given during hospitalization. Following pharmocol-therapy, symptoms gradually improved, and the patient was discharged. Conclusions: The patient was considered disseminated and refractory non-tubercular mycobacterium (NTM) combined with Penicillium marneffei infection. In addition, we found that anti IFN-γ autoantibodies are closely related. Although the current incidence of this patient is related to anti IFN-γ, there is a strong correlation between autoantibody-mediated immunodeficiency in adults.
基金Supported by The Guangxi TCM Suitable Technology Development and Promotion Project,No.GZSY20-20.
文摘BACKGROUND Infections by non-tuberculous mycobacteria(NTM)have become more common in recent years.Mycobacterium canariasense(M.canariasense)was first reported as an opportunistic pathogen in 2004,but there have been very few case reports since then.Nocardia is a genus of aerobic and Gram-positive bacilli,and these species are also opportunistic pathogens and in the Mycobacteriales order.Conventional methods for diagnosis of NTM are inefficient.Metagenomic next-generation sequencing(mNGS)can rapidly detect many pathogenic microorganisms,even rare species.Most NTM and Nocardia infections occur in immunocompromised patients with atypical clinical symptoms.There are no previous reports of infection by M.canariasense and Nocardia farcinica(N.farcinica),especially in immunocompetent patients.This case report describes an immunocompetent 52-year-old woman who had overlapping infections of M.canariasense,N.farcinica,and Candida parapsilosis(C.parapsilosis)based on mNGS.CASE SUMMARY A 52-year-old woman presented with a productive cough and chest pain for 2 wk,and recurrent episodes of moderate-grade fever for 1 wk.She received antibiotics for 1 wk at a local hospital,and experienced defervescence,but the productive cough and chest pain persisted.We collected samples of a lung lesion and alveolar lavage fluid for mNGS.The lung tissue was positive for M.canariasense,N.farcinica,and C.parapsilosis,and the alveolar lavage fluid was positive for M.canariasense.The diagnosis was pneumonia,and application of appropriate antibiotic therapy cured the patient.CONCLUSION Etiological diagnosis is critical for patients with infectious diseases.mNGS can identify rare and novel pathogens,and does not require a priori knowledge.
基金Xinjiang Uygur Autonomous Region Health Youth Medical Science and Technology Talents Special Project(Project number:WJW-202116)。
文摘Objective:To analyze the mutation characteristics of inhA and katG genes in isoniazid-resistant Mycobacterium tuberculosis in Xinjiang.Methods:The katG and inhA in 148 strains of isoniazid-resistant Mycobacterium tuberculosis were amplified through fluorescence quantitative PCR,and the amplified products were sequenced and compared.Results:The inhA gene mutation rate of 148 strains of isoniazid-resistant mycobacterium tuberculosis was 13.51%(20/148),among which the inhA gene mutation rate among patients of Han,Uygur,and Kazakh ethnicity were 15.87%,13.21%,and 17.65%,respectively.There was no significant difference in the inhA mutation rate among nationalities(c^(2)=2.897,P>0.05).The mutation rate of the katG gene was 84.46%(125/148),among which the mutation rates of patients of Han,Uyghur,and Kazak ethnicities were 82.54%,84.91%,and 76.47%,respectively.The Hui and other ethnic groups were all affected by the katG gene mutation.There was no significant difference in the mutation rate of the katG gene among different ethnicities(c^(2)=3.772,P>0.05).The mutation rates of the inhA gene in southern Xinjiang,northern Xinjiang,and other provinces were 18.60%,9.28%,and 37.50%,respectively.The mutation rates of the inhA gene in different regions were statistically different(c^(2)=6.381,P<0.05).There was no significant difference in the inhA mutation rate between patients from southern and northern Xinjiang(c^(2)=2.214,P>0.05)and between southern Xinjiang and other provinces(c^(2)=1.424,P>0.05).However,the mutation rate of the inhA gene in patients from other provinces was higher than that in northern Xinjiang(c^(2)=5.539,P<0.05).The mutation rates of the katG gene in southern Xinjiang,northern Xinjiang,and other provinces were 81.40%,87.63%,and 62.50%,respectively.There was no significant difference in the mutation rates of the katG gene among different regions(c^(2)=3.989,P>0.05).Conclusion:katG gene mutation was predominant in isoniazid-resistant tuberculosis patients in Xinjiang Uygur Autonomous Region,and inhA and katG gene mutation were no different among different ethnic groups.
基金supported by the National Key Programme of Mega Infectious Diseases (2008ZX100/03-010-02)the National Natural Science Funding of China (30800029)
文摘Objective To identify the novel species ‘Mycobacterium fukienense' sp. nov of Mycobacterium chelonoe/abscessus complex from tuberculosis patients in Fujian Province, China. Methods Five of 27 clinical Mycobucterium isolates (CIs) were previously identified as M. chelonoe/obscessus complex by sequencing the hsp65, rpoB, 165-235 rRNA internal transcribed spacer region (its), recA and sodA house-keeping genes commonly used to describe the molecular characteristics of Mycobocterium. Clinical Mycobecterium isolates were classified according to the gene sequence using a clustering analysis program. Sequence similarity within clusters and diversity between clusters were analyzed. Results The 5 isolates were identified with distinct sequences exhibiting 99.8% homology in the hsp65 gene. However, a complete lack of homology was observed among the sequences of the rpoB, 165-235 rRNA internal tronscribed spacer region (its), sodA, and recA genes as compared with the M. obscessus. Furthermore, no match for rpoB, sodA, and recA genes was identified among the published sequences. Conclusion The novel species, Mycobacterium fukienense, is identified from tuberculosis patients in Fujian Province, China, which does not belong to any existing subspecies of M. cheloneo/abscessus complex.
基金supported by National Natural Science Foundation of China (No.30470097,No.30500432)
文摘Resuscitation promoting factor E (RpfE) is one of the five Rpf-like proteins in Mycobacterium tuberculos& (M. tuberculosis). These Rpf-like proteins are secretory, which make them candidates for recognition by the host immune system. In this study, the RpfE gene was amplified from M. tuberculosis, cloned into the expression vectors pDE22 and pPRO EXHT, and were expressed in Mycobacterium vaccae (M. vaccae) and Escherichia coli DHSa, respec- tively. Both recombinant RpfE proteins were purified by Ni-Sepharose affinity chromatography, and were given to C57BL/6 mice. The RpfE proteins elicited T cell proliferation, and stimulated the production of gamma interferon (IFN-y), interleukin-10 (IL-10) and IL-12. Our results indicated that the RpfE protein expressed in M. vaccae could more efficiently stimulate cellular immune response, making it a promising candidate as a subunit vaccine.
基金supported by the project 81401647 of Natural Science Foundation of ChinaProject 2014SKLID104 of State Key Laboratory for Infectious Diseases Prevention and Controlprojects 16411967900 of Science and Technology Commission of Shanghai Municipality
文摘Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study. Methods Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay. Results Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacteriurn elephantis (M. elephantis). The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. Conclusion To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China.
文摘Mycobacterium paragordonae(M.paragordonae),a slow-growing,acid-resistant mycobacterial species,was first isolated from the sputum of a lung infection patient in South Korea in 2014.Infections caused by M.paragordonae are rare.CASE SUMMARY Herein,we report the case of a 53-year-old patient who presented with fever and low back pain.Lumbar nuclear magnetic resonance imaging revealed the destruction of the lumbar vertebra with peripheral abscess formation.After antiinfective and diagnostic anti-tuberculosis treatment,the patient had no further fever,but the back pain was not relieved.Postoperatively,the necrotic material was sent for pathological examination,and all tests related to tuberculosis were negative,but pus culture suggested nontuberculous mycobacteria.The necrotic tissue specimens were subjected to metagenomic next-generation sequencing,which indicated the presence of M.paragordonae.Finally,the infecting pathogen was identified,and the treatment plan was adjusted.The patient was in good condition during the follow-up period.CONCLUSION M.paragordonae,a rare nontuberculous mycobacterium,can also cause spinal infections.In the clinic,it is necessary to identify nontuberculous mycobacteria for spinal infections similar to Mycobacterium tuberculosis.
基金This research was supported by the National Key Research and Development Program of China(2021YFD1800403)the National Natural Science Foundation of China(32273005 and 32002256).
文摘The serine proteases of Mycobacteria tuberculosis(Mtb)are important contributors to the process of bacterial invasion and its pathogenesis.In the present study,we systematically characterized the role of the Rv1043c protein in Mycobacterium infection by purifying the Rv1043c protein in Escherichia coli and constructing a Mycobacterium smegmatis(Msg)strain overexpressing Rv1043c(Msg_Rv1043c).We found that Rv1043c had serine protease activity and localized to the surface of Mtb.We determined that the optimal pH and temperature for the Rv1043c serine protease were 9.0 and 45°C,respectively.Moreover,the serine protease activity of Rv1043c was enhanced by divalent metal ions of Ca^(2+)and Mg^(2+).Site-directed mutagenesis studies demonstrated that the serine 279 residue in Rv1043c plays a catalytic role.Additionally,mouse model studies confirmed that Rv1043c significantly enhanced the survival of Msg in vivo,induced pulmonary injury and lung cell apoptosis,and promoted the release of pro-inflammatory cytokines interleukin-1βand interleukin-6 in mice.This study presents novel insights into the relationship between mycobacterial serine protease and the pathogenesis of the disease.
基金The Scientific Research Project of Peking University Shenzhen Hospital,No.JCYJ2018011the San-ming Project of Medicine in Shenzhen,No.SZSM201812059.
文摘BACKGROUND The incidence of infection with Mycobacterium abscessus(M.abscessus)has increased in recent years.This increase is partly associated with invasive cosmetic procedures.CASE SUMMARY The purpose of this case summary is to increase clinicians'awareness of M.abscessus infection and reduce mycobacterial infection caused by cosmetic procedures.We report the case of a 45-year-old woman who received acetyl hexapeptide-8(argireline)injections in the forehead and temples,and erythema,nodules,and abscesses appeared at the injection sites after one week.The pus specimens were examined by microbiological culture and confirmed to be positive for M.abscessus.Clarithromycin 500 mg twice daily and moxifloxacin 400 mg once daily were administered for 5 mo and the lesions gradually subsided.CONCLUSION We report here for the first time a case of infection with M.abscessus after argireline injection.This condition is easily misdiagnosed as a common bacterial infection.Microbiological examinations are helpful for diagnosis and standardized cosmetic procedures can prevent infection with M.abscessus.