Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy

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.

Molecular Identification of Mycobacterium Strains Responsible of Bovine Tuberculosis Cases in Bobo-Dioulasso Slaughterhouse, Burkina Faso

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.

Epidemiology and Clinical Features of Mycobacterium avium Complex Pulmonary Disease in a Brazilian Amazon Cohort

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.

Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

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.

Tuberculosis in the Carcinal Environment in Chad Due to the Mycobacterium Tuberculosis Circulante Complex

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.

Early Prosthetic Valve Endocarditis with Mycobacterium Tuberculosis after Mitral Valve Replacement: A Case Report

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.

Mycobacterium gordoniasis of the cervical lymph nodes:A case report

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.

Metagenomic next-generation sequencing may assist diagnosis of osteomyelitis caused by Mycobacterium houstonense:A case report

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.

Overlapping infections of Mycobacterium canariasense and Nocardia farcinica in an immunocompetent patient:A case report

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.

Mutation Characteristics of inhA and katG Genes in Isoniazid-Resistant Mycobacterium Tuberculosis Patients in Xinjiang

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.

Prevalence of non-tuberculosis mycobacteria among samples deposited from the National Tuberculous Reference Laboratory of Iran(2011-2018)

Objective:To investigate the prevalence of non-tuberculosis mycobacteria(NTM)among the samples deposited from the National Tuberculosis Reference Laboratory of Iran between 2011 and 2018.Methods:The study evaluated the prevalence of NTM among specimens from patients with pulmonary tuberculosis symptoms(n=15771)deposited at the National Tuberculosis Reference Laboratory of Iran from 2011 to 2018.Detection of Mycobacterium(M.)tuberculosis was based on presence of a 190-bp amplicon from IS6110 insertion sequence using Tb1 and Tb2 primers,and amplicon-negative specimens were tested for NTM and M.tuberculosis(refractory to IS6110 amplification)using restriction fragment length polymorphism PCR of hsp65 amplicon fragment.Results:A total of 7307(46.33%)M.tuberculosis and 658(4.17%)NTM specimens were found,the latter mainly comprising M.abscessus(10.18%),M.avium(2.28%),M.chelonae(8.97%),M.intracellulare(10.49%),M.kansasii(4.71%),and M.simiae(56.08%).Conclusions:As treatment for NTM differs from that for M.tuberculosis,accurate detection of Mycobacterium sp.is of public health significance.

Characteristics of Mycobacterium tuberculosis serine protease Rv1043c in enzymology and pathogenicity in mice

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.

四川省2022年入学新生结核分枝杆菌潜伏感染与肺结核患病情况分析

目的:对2022年四川省入学新生结核病体检情况进行汇总和分析,了解全省入学新生结核分枝杆菌潜伏感染(latent tuberculosis infection,LTBI)与结核病患病情况,为学校新生入学结核病检查工作开展提供理论依据。方法:从四川省学籍管理系统中获得2022年全省各级各类学校入学新生基本信息,制作《2022年秋季新生入学结核病体检信息表》,建立数据库,采用描述性统计分析方法,分析新生入学结核病检查中结核病患者及LTBI者检出情况及其流行病学特征,追踪LTBI者接受预防性治疗及完成情况。结果:2022年四川省各级各类学校入学新生2787900名规范开展结核病体检,占全部新生的97.69%(2787900/2853817),发现活动性肺结核患者247例,检出率为8.86/10万(247/2787900)。其中,女性患病率为10.11/10万(145/1434131),高于男性[7.18/10万(102/1419686)],差异有统计学意义(χ^(2)=7.058,P<0.01)。四川省1790830名入学新生开展了LTBI检测,感染率为3.09%(55313/1790830)。符合预防性治疗条件的单纯结核菌素皮肤试验强阳性/重组结核分枝杆菌融合蛋白(EC)或γ-干扰素释放试验阳性者8104例中,13.73%(1113/8104)接受了预防性治疗,925例完成了全疗程,完成治疗率为83.11%,未完成治疗的新生中有2例在治疗期间转为活动性结核病。结论:四川省2022年入学新生体检率高,但LTBI检出率较低,接受预防性治疗率不高。

Evaluation of Microsphere-based xMAP Test for gyrA Mutation Identification in Mycobacterium Tuberculosis

Drug-resistant(DR) tuberculosis(TB) is a growing threat to public health[1]. Fluoroquinolone(FQ) antibiotics have long been used as anti-tuberculosis drugs, and their widespread application has led to the development of resistance in clinical isolates of Mycobacterium tuberculosis complex(MTBC).

Contribution to the Study of Resistance to Anti-Tuberculosis Drugs in the Mycobacterium tuberculosis Complex Isolated at the National Laboratory of Clinical Biology and Public Health in Bangui in the Central African Republic in 2022: Case of Rifampicin

Microscopy-positive and drug-resistant pulmonary tuberculosis (MPT+) is one of the most feared diseases due to the cost of its management and the associated mortality. The GeneXpert, a new molecular test, is in greater demand for the diagnosis of MPT+ resistance cases. The application of GeneXpert to new cases of MPT+ is not effective in the country’s TB screening centres. The objective of this study is to assess the contribution of GeneXpert to the determination of MPT+ resistance cases in Bangui. The study was cross-sectional and covered the period from February to July 2022. The diagnosis of tuberculosis was first performed by microscopy with Ziehl Neelsen hot stain. The GeneXpert was then used to test for resistance in the sputum of all patients with positive microscopy. The collected data was entered into Excel 2013 and analysed with Epi Info 3.3.7. We analysed data from 755 patients, 80 of whom had resistance. The 80 patients ranged in age from 6 to 68 years (mean age = 35 years). The prevalence of resistant TB was 10.60% (80/755). Primary resistance accounted for 73.75% and secondary resistance for 26.25%. The age group 20 - 39 years (57.50%), male (72.50%), 8th district (17.50%), people living in couples (53.75%), farmers (13.75%) were the socio-demographic characteristics most affected by resistance. Treatment failure (13.75%), relapses (13.75%), the notion of contagion (28.75%), a history of smoking (40%) and alcohol (61.25%) were the clinical antecedents reported by the patients. Treatment failure and relapse were the variables associated with the occurrence of resistant PMT+ (p 0.05). A considerable proportion of the overall Mycobacterium tuberculosis resistance to anti-tuberculosis drugs (10.60%) was identified by GeneXpert. Treatment failure and relapse were the factors associated with the risk of resistance.

Characterization of Mutations in Genes Related to Rifampicin and Isoniazid Resistance in Multidrug-resistant Mycobacterium tuberculosis Strains from Hangzhou,China

Tuberculosis(TB),caused by the Mycobacterium tuberculosis complex(MTBC),is the 13^(th)leading cause of death and the second leading cause of infectious killer after COVID-19(above HIV and AIDS),according to the World Health Organization's 2022 Global TB Report.In 2021,10.6 million people were diagnosed with a new episode of TB and 1.6 million people died as a result.

Characterization of Mycobacterium Species Circulating among Tuberculosis Patients in Bayelsa State, Nigeria

Introduction: Tuberculosis is caused by infection with Mycobacterium tuberculosis. Looking at the evolution of the bacterium gene due to mutation is crucial to identify species circulating among patients in an area. WHO speculated that tuberculosis is caused by M. tuberculosis (MTB), but identification of the strains of MTB circulating in a particular area is important for the management of MTB and to identify pulmonary infections caused by non-tuberculosis mycobacterium. Contact tracing of drug resistant MTB in circulation in an area is also an important procedure of MTB therapeutic choice. Aim: This study aimed to isolate and identify Mycobacterium species circulating in Bayelsa State, Nigeria. Materials and Methods: A total of 102 sputum samples collected from MTB patients were cultured in Lowenstein Jensen (LJ) solid media. Isolates on LJ media were confirmed using Zeihl Nelseen staining method for AFB and Standard Diagnosis Bioline TB Ag MPT64 Rapid test kit. The 16s rRNA gene amplification, agarose gel electrophoresis, and gene sequencing were conducted. Phylogenic analysis and evolutional distances of the strains are computed using the Juke-cantor method. Result: Out of 102 sputum samples examined 15 (14.7%) had growth of Mycobacterium species (AFB positive). The extracted DNA of MTB amplified on agarose gel electrophoresis aligned horizontally at lanes 1 - 15 showing 16S gene band (1500 bp). Two 2 (2.0%) are non-tuberculosis Mycobacteria species, while 13 (12.7%) were M. tuberculosis. The non-tuberculosis Mycobacterium species isolated are Mycobacteriode abscesses and Mycobacterium kansassii strain FDAARGOS 1534. The tuberculosis strains are Mycobacterium tuberculosis MG003 and R2092 but the predominant strain was MG003. The degree of the genetic evolution of the non-MTB Mycobacterium kansassii strain FDAARGOS 1534 was 75.4%. Conclusion: The two major strains of Mycobacterium tuberculosis (MTB) circulating in Bayelsa State are MTB MG003 and MTB R2092;MTB MG003 was predominant. The non-tuberculosis species are Mycobacteriode abscesses and Mycobacterium kansasii.

Involvement of 2'-5'oligoadenylate synthetase-like proteinin the survivalof Mycobacterium tuberculosis avirulent strain in macrophages

Mycobacterium tuberculosis(M.tuberculosis)can replicate in the macrophage by interfering with many host protein functions.While it is far from known these host proteins for controlling M.tuberculosis infection.Herein,we infected macrophages including THP-1 and Raw264.7 cells with M.tuberculosis and identified the differentially expressed genes(DEGs)in the interferon signaling pathway.Among them,2'-5'oligoadenylate synthetase-like(OASL)underwent the greatest upregulation in M.tuberculosis-infected macrophages.Knockdown of the expression of OASL attenuated M.tuberculosis survival in macrophages.Further,bioinformatics analysis revealed the potential interaction axis of OASL-TAB3-RvO127,which was further validated by the yeast-two-hybrid(Y2H)assay and Co-IP.This interaction axis might regulate the M.tuberculosis survival and proliferation in macrophages.The study reveals a possible role of OASL during M.tuberculosis infection as a target to control its propagation.

Research progress on the drug action and resistance mechanism in Mycobacterium tuberculosis

Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.

Value of ultrasound guided biopsy combined with Xpert Mycobacterium tuberculosis/resistance to rifampin assay in the diagnosis of chest wall tuberculosis

BACKGROUND The thoracic wall lesions,particularly chest wall tuberculosis,and chest wall tumors and other pyogenic wall and actinomycetes infections,almost always present as a diagnostic challenge.AIM To explore the value of ultrasound-guided biopsy combined with the Xpert Mycobacterium tuberculosis/resistance to rifampin(MTB/RIF)assay to diagnose chest wall tuberculosis.METHODS We performed a retrospective study of patients with chest wall lesions from March 2018 to March 2021.All patients received the ultrasound-guided biopsy for pathology examination,acid-fast Bacillus staining,mycobacterial culture,and Xpert MTB/RIF analysis.The sensitivity,specificity,and area under the curve(AUC)were calculated for these diagnostic tests,either individually or combined.Rifampicin resistance results were compared between the mycobacterial culture and the Xpert MTB/RIF assay.RESULTS In 31 patients with the chest wall lesion biopsy,22 patients were diagnosed with chest wall tuberculosis.Of them,3,6,and 21 patients tested positive for mycobacterial culture,acid-fast stain,and Xpert MTB/RIF assay,respectively.The rifampicin resistance results of the 3 culture-positive patients were consistent with their Xpert MTB/RIF assay results.When considering the sensitivity,specificity,and AUC value,the Xpert MTB/RIF assay(95.5%,88.9%,and 0.92,respectively)was a better choice than the acid-fast Bacillus stain(27.3%,100.0%,and 0.64,respectively)and mycobacterial culture(13.6%,100.0%,0.57,respectively).No complications were reported during the procedure.CONCLUSION Ultrasound guided biopsy combined with Xpert MTB/RIF has high value in the diagnosis of chest wall tuberculosis,and can also detect rifampicin resistance.