Management of Polydrug-Resistant Tuberculosis.

Background and Objectives: There is a lack of information regarding the effective duration of treatment necessary to prevent the development of acquired resistance when fluoroquinolones (FQ), and/or pyrazinamide (Z) resistance has occurred in patients with polydrug-resistant tuberculosis and isoniazid resistance. The management of these kinds of patients should be carried out in experienced centers according to drug susceptibility test results, clinical status of the patient and the extensity of the disease. Materials and Methods: We evaluated treatment regimens, treatment outcomes, and drug adverse effects in seven patients with polydrug-resistant tuberculosis, including those with Z and/or FQ resistance in a retrospective analysis Results: Regarding the patients with polydrug-resistant tuberculosis in addition to isoniazid (H) resistance, three had Z, two had FQ, and the remaining two had both Z and FQ resistance. In the intensive phase of the treatment, the patients were given at least four drugs according to drug susceptibility tests, and at least three drugs in the continuation phase. The duration of treatment was 9-12 months. Two of the patients were foreign nationals, and could not be followed up with due to returning to their home countries. Regarding the remaining five patients, three of them were terminated as they completed treatment, and two as cured. No recurrence was observed in the first year of the treatment. The most common, and serious drug side effect was seen for amikacin. Conclusions: In patients with polydrug-resistant TB, if Z and/or FQ resistance is detected in addition to H resistance, the treatment of these patients should be conducted on a case-by-case basis, taking into account the patient's resistance pattern, clinical condition, and disease prognosis. Close monitoring of the side effects will increase the success rate of the treatment.

Immunomodulatory agents for COVID-19 treatment: possible mechanism of action and immunopathology features.

The novel coronavirus pandemic has emerged as one of the significant medical-health challenges of the current century. The World Health Organization has named this new virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first detection of SARS-CoV-2 in November 2019 in Wuhan, China, physicians, researchers, and others have made it their top priority to find drugs and cures that can effectively treat patients and reduce mortality rates. The symptoms of Coronavirus Disease 2019 (COVID-19) include fever, dry cough, body aches, and anosmia. Various therapeutic compounds have been investigated and applied to mitigate the symptoms in COVID-19 patients and cure the disease. Degenerative virus analyses of the infection incidence and COVID-19 have demonstrated that SARS-CoV-2 penetrates the pulmonary alveoli's endothelial cells through Angiotensin-Converting Enzyme 2 (ACE2) receptors on the membrane, stimulates various signaling pathways and causes excessive secretion of cytokines. The continuous triggering of the innate and acquired immune system, as well as the overproduction of pro-inflammatory factors, cause a severe condition in the COVID-19 patients, which is called "cytokine storm". It can lead to acute respiratory distress syndrome (ARDS) in critical patients. Severe and critical COVID-19 cases demand oxygen therapy and mechanical ventilator support. Various drugs, including immunomodulatory and immunosuppressive agents (e.g., monoclonal antibodies (mAbs) and interleukin antagonists) have been utilized in clinical trials. However, the studies and clinical trials have documented diverging findings, which seem to be due to the differences in these drugs' possible mechanisms of action. These drugs' mechanism of action generally includes suppressing or modulating the immune system, preventing the development of cytokine storm via various signaling pathways, and enhancing the blood vessels' diameter in the lungs. In this review article, multiple medications from different drug families are discussed, and their possible mechanisms of action are also described.

SARS-CoV-2 cell entry beyond the ACE2 receptor.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly correspond with the level of ACE2 expression in the organs. It may suggest involvement of other receptors or accessory membrane proteins in SARSCoV-2 cell entry. METHODS AND RESULTS: A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting SARS-CoV-2 cell entry. We used a group of the MeSH terms including "cell entry", "surface receptor", "ACE2", and "SARS-CoV-2". We reviewed all selected papers published in English up to end of February 2022. We found several receptors or auxiliary membrane proteins (including CD147, NRP-1, CD26, AGTR2, Band3, KREMEN1, ASGR1, ANP, TMEM30A, CLEC4G, and LDLRAD3) along with ACE2 that facilitate virus entry and transmission. Expression of Band3 protein on the surface of erythrocytes and evidence of binding with S protein of SARS-CoV-2 may explain asymptomatic hypoxemia during COVID19 infection. The variants of SARS-CoV-2 including the B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.2+ (Delta+), and B.1.1.529 (Omicron) may have different potency to bond with these receptors. CONCLUSIONS: The high rate of infectivity of SARS-CoV-2 may be due to its ability to enter the host cell through a group of cell surface receptors. These receptors are potential targets to develop novel therapeutic agents for SARS-CoV-2.

Anti-inflammatory Properties of the Alpha-Melanocyte-Stimulating Hormone in Models of Granulomatous Inflammation.

PURPOSE: Alpha-melanocyte stimulating hormone (α-MSH) is known to have anti-inflammatory effects. However, the anti-inflammatory properties of α-MSH on normal bronchial epithelial cells are largely unknown, especially in the context of in vitro sarcoidosis models. METHODS: We evaluated the anti-inflammatory effects of α-MSH on two different in vitro sarcoidosis models (lung-on-membrane model; LOMM and three-dimensional biochip pulmonary sarcoidosis model; 3D-BSGM) generated from NBECs and an in vivo sarcoidosis mouse model. RESULTS: Treatment with α-MSH decreased inflammatory cytokine levels and downregulated type I interferon pathway genes and related proteins in LOMM and 3D-BSGM models. Treatment with α-MSH also significantly decreased macrophages and cytotoxic T-cells counts in a sarcoidosis mice model. CONCLUSION: Our results confirm the direct role of type I IFNs in the pathogenesis of sarcoid lung granulomas and highlight α-MSH as a potential novel therapeutic agent for treating pulmonary sarcoidosis.

COVID-19 in patients with and without acute kidney injury.

BACKGROUND AND OBJECTIVE: SARS-CoV-2 as the newest member of Beta-Coronaviruses can cause a complicated disease called COVID-19. This virus is able to penetrate a broad range of human cells, such as liver, heart, and kidney cells via ACE2-associated endocytosis. Heart involvement can result in kidney injuries; it is now testified that kidney congestion occurs following the cardio-renal syndrome. Acute Kidney Injury is one of the most critical damages to the kidney in a wide range of COVID-19-caused kidney injuries (which includes proteinuria, hematuria, etc.). Examination of AKI risk factors in COVID-19 patients can assist physicians to prevent its incidence. The final aim of this systematic review was to collate the condition and risk factors of AKI and non-AKI COVID-19 patients and to investigate AKI incidence in high-risk patients. METHOD: A complete and comprehensive survey was performed by reviewing original articles and case reports indexed in various databases such as PubMed/Medline, Embase, and WoS to find appropriate articles. The eligible articles then were selected by two authors and entered into the evaluation process. This systematic review conforms PRISMA statement. RESULTS: After searching for potentially relevant articles, 14 out of the initial 463 articles from 6 countries were selected and evaluated. All of eligible articles have investigated the rate of AKI incidence and its physio-pathological consequences in COVID-19 patients in all conditions (not only patients in critical condition). First, the initial differences between AKI and non-AKI patients were compared. As an instance, our study revealed that mean of White Blood cells (WBC) was much higher in AKI patients which can be responsible for the severe conditions. Then, other variations like differences in laboratory and imaging findings were compared between these two groups. Our outcomes demonstrated that the presence of diabetes mellitus (DM), hypertension (HTN), and male sex can be three significant risk factors in AKI incidence in COVID-19 patients. Fatality rate and treatment methods were also compared among these two groups. CONCLUSION: As one of kidney damages, AKI can worsen COVID-19 patients' status by causing conditions such as acidosis. Our study shows the common symptoms in AKI COVID-19 patients were fever, cough, and malaise. The results of our study can help physicians to arrange COVID-19 with AKI patients' treatment strategy precisely (Tab. 8, Fig. 1, Ref. 48).

Nontuberculous Mycobacteria, Macrophages, and Host Innate Immune Response.

Although nontuberculous mycobacteria (NTM) are considered opportunistic infections, incidence and prevalence of NTM infection are increasing worldwide becoming a major public health threat. Innate immunity plays an essential role in mediating the initial host response against these intracellular bacteria. Specifically, macrophages phagocytose and eliminate NTM and act as antigen-presenting cells, which trigger downstream activation of cellular and humoral adaptive immune responses. Identification of macrophage receptors, mycobacterial ligands, phagosome maturation, autophagy/necrosis, and escape mechanisms are important components of this immunity network. The role of the macrophage in mycobacterial disease has mainly been studied in tuberculosis (TB), but limited information exists on its role in NTM. In this review, we focus on NTM immunity, the role of macrophages, and host interaction in NTM infection.

Machine-learning-based COVID-19 mortality prediction model and identification of patients at low and high risk of dying.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-Cov2 virus has become the greatest health and controversial issue for worldwide nations. It is associated with different clinical manifestations and a high mortality rate. Predicting mortality and identifying outcome predictors are crucial for COVID patients who are critically ill. Multivariate and machine learning methods may be used for developing prediction models and reduce the complexity of clinical phenotypes. METHODS: Multivariate predictive analysis was applied to 108 out of 250 clinical features, comorbidities, and blood markers captured at the admission time from a hospitalized cohort of patients (N = 250) with COVID-19. Inspired modification of partial least square (SIMPLS)-based model was developed to predict hospital mortality. Prediction accuracy was randomly assigned to training and validation sets. Predictive partition analysis was performed to obtain cutting value for either continuous or categorical variables. Latent class analysis (LCA) was carried to cluster the patients with COVID-19 to identify low- and high-risk patients. Principal component analysis and LCA were used to find a subgroup of survivors that tends to die. RESULTS: SIMPLS-based model was able to predict hospital mortality in patients with COVID-19 with moderate predictive power (Q2 = 0.24) and high accuracy (AUC > 0.85) through separating non-survivors from survivors developed using training and validation sets. This model was obtained by the 18 clinical and comorbidities predictors and 3 blood biochemical markers. Coronary artery disease, diabetes, Altered Mental Status, age > 65, and dementia were the topmost differentiating mortality predictors. CRP, prothrombin, and lactate were the most differentiating biochemical markers in the mortality prediction model. Clustering analysis identified high- and low-risk patients among COVID-19 survivors. CONCLUSIONS: An accurate COVID-19 mortality prediction model among hospitalized patients based on the clinical features and comorbidities may play a beneficial role in the clinical setting to better management of patients with COVID-19. The current study revealed the application of machine-learning-based approaches to predict hospital mortality in patients with COVID-19 and identification of most important predictors from clinical, comorbidities and blood biochemical variables as well as recognizing high- and low-risk COVID-19 survivors.

Long-term exposure to indoor air pollution and risk of tuberculosis.

Indoor air pollution (IAP) is a recognized risk factor for various diseases. This paper examines the role of indoor solid fuel exposure in the risk of mycobacterium tuberculosis (TB) in Delhi Metropolitan, India. Using a cross-sectional design, subjects were screened for a history of active TB and lifelong exposure to IAP sources, such as solid fuel burning and kerosene. The TB prevalence rate in the study area was 1117 per 100 000 population. Every year, increase in solid fuel exposure was associated with a three percent higher likelihood of a history of active TB. Subjects exposed to solid fuel and kerosene use for both heating home and cooking showed significant associations with TB. Age, household expenditure (a proxy of income), lung function, and smoking also showed significant associations with TB. Smokers and solid fuel-exposed subjects were four times more likely to have a history of active TB than non-smoker and unexposed subjects. These finding calls strategies to mitigate solid fuel exposure, such as use of clean cookstove and ventilation, to mitigate the risk of TB which aligns with the United Nations' goal of "End TB by 2030."

Pulmonary nontuberculous mycobacterial disease in Florida and association with large-scale natural disasters.

BACKGROUND: Little is known about the impact of the ecosystem disruption and its contribution on the non-tuberculosis mycobacteria (NTM) diseases (cases) rate in Florida (FL), a state with a high prevalence of NTM in the United States. We aimed to evaluate the epidemiological distribution of NTM in FL and identify its association with extreme weather events. METHODS: We used OneFlorida Clinical Research Consortium dataset and extracted data on NTM cases using ICD codes 9- CM 031.0 and ICD-10 A31 during 2012-2018. The number of hurricanes during the study period which affected FL were extracted data from the National Hurricane Center (NHC) and the National Oceanic and Atmospheric Administration (NOAA). RESULTS: Prevalence of NTM gradually increased during the study period. The rate was 2012: 14.3/100,000, 2015; 20.1/100,000 and 2018; 22.6/100,00 except in 2014 where there was an 8% decrease. The incidences were 2012; 6.5/100,00, 2015; 4.9/100,000 and in 2015; 5.4/100,000. Geographical analysis demonstrated a gradual expansion of the NTM cases in Alachua, and Marion Counties throughout the study period. Notably, the 2018 heat map showed higher prevalence of NTM in the northwestern, panhandle region of FL which had been absent in the heat maps for years 2012-2018. High number of the hurricanes was associated with the higher number of the new cases of NTM infection for years 2012, 2016-2018, while the lower number of the hurricanes was associated with the lower number of the new cases of NTM infection for years 2014-2015. CONCLUSION: The current study found the prevalence rates of NTM disease in FL rose from 2012 to 2018. A higher prevalence was seen following the hurricanes.

Association of Serum Albumin and Severity of Pulmonary Embolism.

Background and Objectives: Inflammation is considered a risk factor for venous thromboembolism. The association between inflammatory markers and the severity of acute pulmonary embolism (APE) has not been explored. Methods: We studied the association between two crude markers of inflammation, serum albumin, and red cell distribution width (RDW) and massive versus non-massive APE. Results: Among 552 consecutive cases of CT-angiogram-confirmed APE, a total of 46 cases (8.3%) had massive APE. Despite similar demographics and comorbidities, patients with massive APE had higher frequency of acute kidney injury (P = 0.005), higher lactic acid (P = 0.011), higher troponin (P = 0.001), higher BNP (P < 0.001), higher frequency of RV dilation (P = 0.017) and hypokinesis (P = 0.003), and higher in-hospital mortality (15.2% vs. 2%, P < 0.001). Patients with massive APE had significantly lower albumin level (median (IQR): 2.8 (2.2, 3.0) vs. 3.2 (2.8, 3.6) gm/dL, P < 0.001) and higher RDW (median (IQR): 14.7 (13.8, 17.1) vs. 14.2 (13.3, 15.6), P = 0.006) compared with non-massive APE. ROC curves showed that albumin and RDW had an AUC of 0.750 (P < 0.001) and 0.621 (P = 0.006) in predicting a massive APE, respectively. The optimal cutoff values for albumin and RDW that had the highest combined sensitivity and specificity for predicting APE was ≤3 gm/dL and >14, for albumin and RDW, respectively. Restricted cubic splines showed a significant association between albumin (P = 0.0002) and RDW (P = 0.0446) and the occurrence of massive APE. After adjustment for patients' age, body mass index, white blood cell count, the requirement of antibiotics during hospitalization, diabetes, RDW, and peak creatinine, serum albumin was independently associated with massive APE (OR 0.234, 95% CI 0.129-0.4242, P < 0.001). Conclusion: low serum albumin is associated with massive APE. This association is likely a proxy for higher inflammatory state in massive compared with non-massive APE.

Mycobacterium avium complex infection in patients with human immunodeficiency virus: A systematic review and meta-analysis.

BACKGROUND: Mycobacterium avium-intracellulare complex (MAC) is one of the leading causes of death among people living with human immunodeficiency virus (HIV). The current study was aimed to determine the frequency of MAC infection in patients infected with HIV. METHODS: Embase, PubMed, and Web of Science were searched for relevant studies. All statistical analyses were performed by STATA version 14. RESULTS: From 6,627 retrieved articles, 23 were included in the final analysis. A total of 18,463 patients with HIV were included in the analysis. The frequency of MAC infection in patients with HIV was found to be 10.6% (95% confidence interval, 6.9-14.2). CONCLUSION: The relatively large fractions of HIV-infected patients were coinfected with MAC, which may poses significant public health problems. Continued progress in the development of rapid diagnostic methods and preventive therapy for MAC should lead to further improvements in survival and quality of life in patients with HIV.

Rescue therapy for hypercapnia due to high PEEP mechanical ventilation in patients with ARDS and renal failure.

Extracorporeal removal of carbon dioxide in patients experiencing severe hypercapnia due to lung protective mechanical ventilation was first described over four decades ago. There have been many devices developed and described in the interim, many of which require additional training, resources, and staff. This manuscript describes a readily available and relatively simple adjunct that can provide partial lung support in patients with acute respiratory distress syndrome complicated by severe hypercapnia and acute kidney injury requiring dialysis.

Growth Hormone-Releasing Hormone Receptor Antagonist Modulates Lung Inflammation and Fibrosis due to Bleomycin.

PURPOSE: Growth hormone-releasing hormone (GHRH) is a 44-amino acid peptide that regulates growth hormone (GH) secretion. We hypothesized that a GHRH receptor (GHRH-R) antagonist, MIA-602, would inhibit bleomycin-induced lung inflammation and/or fibrosis in C57Bl/6J mice. METHODS: We tested whether MIA-602 (5 µg or vehicle given subcutaneously [SC] on days 1-21) would decrease lung inflammation (at day 14) and/or fibrosis (at day 28) in mice treated with intraperitoneal (IP) bleomycin (0.8 units on days 1, 3, 7, 10, 14, and 21). Bleomycin resulted in inflammation and fibrosis around airways and vessels evident histologically at days 14 and 28. RESULTS: Inflammation (histopathologic scores assessed blindly) was visibly less evident in mice treated with MIA-602 for 14 days. After 28 days, lung hydroxyproline (HP) content increased significantly in mice treated with vehicle; in contrast, lung HP did not increase significantly compared to naïve controls in mice treated with GHRH-R antagonist. GHRH-R antagonist increased basal and maximal oxygen consumption of cultured lung fibroblasts. Multiple genes related to chemotaxis, IL-1, chemokines, regulation of inflammation, and extracellular signal-regulated kinases (ERK) were upregulated in lungs of mice treated with bleomycin and MIA-602. MIA-602 also prominently suppressed multiple genes related to the cellular immune response including those for T-cell differentiation, receptor signaling, activation, and cytokine production. CONCLUSIONS: MIA-602 reduced lung inflammation and fibrosis due to bleomycin. Multiple genes related to immune response and T-cell functions were downregulated, supporting the view that MIA-602 can modulate the cellular immune response to bleomycin lung injury.

Noncoding RNAs: New Players in Pulmonary Medicine and Sarcoidosis.

Noncoding RNAs (ncRNAs) are coded by 98% of human genomic DNA. They are grouped into two major classes according to length: small ncRNAs and long ncRNAs. They regulate genome organization, stability, and physiological processes that maintain cellular homeostasis. Recently, great interest has emerged in ncRNAs because of their significant roles in the development of inflammatory diseases, including sarcoidosis. Some have been introduced as novel markers for disease activity, such as increased levels of microRNA-34a in peripheral blood mononuclear cells of patients with sarcoidosis, re-emphasizing the inflammatory component in sarcoidosis. They are also important factors in the outcome of sarcoidosis. Dysregulation of microRNA-let7f leads to overexpression of profibrotic factors and could be related to the pathogenesis of pulmonary fibrosis in patients with sarcoidosis, owing to their stimulatory effect on collagen expression and deposition. However, many unanswered questions remain about the association of ncRNAs and sarcoidosis. By understanding the functions of ncRNAs in T-helper cell type 1 and T-helper cell type 17, we may uncover the mechanism of action of those cells in sarcoidosis. Further translational research is needed to define the RNA gene fingerprint of different sarcoidosis stages.

Diagnosis of nontuberculous mycobacterial disease in the era of surveillance chest CT scans.

The radiologic surveillance of smokers with low-dose CT scan has led to a significant surge of radiologic incidental findings, including the detection of early stages of pulmonary infections including nontuberculous mycobacteria (NTM). This causes a state of overdiagnosis and potential overtreatment of NTM lung disease. Here we propose a new approach to NTM pulmonary disease in the era of increased CT scanning.

Lung health in era of climate change and dust storms.

Dust storms are strong winds which lead to particle exposure over extensive areas. These storms influence air quality on both a local and global scale which lead to both short and long-term effects. The frequency of dust storms has been on the rise during the last decade. Forecasts suggest that their incidence will increase as a response to the effects of climate change and anthropogenic activities. Elderly people, young children, and individuals with chronic cardiopulmonary diseases are at the greatest risk for health effects of dust storms. A wide variety of infectious and non-infectious diseases have been associated with dust exposure. Influenza A virus, pulmonary coccidioidomycosis, bacterial pneumonia, and meningococcal meningitis are a few examples of dust-related infectious diseases. Among non-infectious diseases, chronic obstructive pulmonary disease, asthma, sarcoidosis and pulmonary fibrosis have been associated with dust contact. Here, we review two molecular mechanisms of dust induced lung disease for asthma and sarcoidosis. We can also then further understand the mechanisms by which dust particles disturb airway epithelial and immune cells.

Syncope on presentation is a surrogate for submassive and massive acute pulmonary embolism.

INTRODUCTION: There are conflicting data regarding the prognostic value of syncope in patients with acute pulmonary embolism (APE). METHODS: We retrospectively reviewed data of 552 consecutive adults with computed tomography pulmonary angiogram-confirmed APE to determine the correlates and outcome of the occurrence of syncope at the time of presentation. RESULTS: Among 552 subjects with APE (mean age 54years, 47% men), syncope occurred in 12.3% (68/552). Compared with subjects without syncope, those with syncope were more likely to have admission systolic blood pressure<90mmHg (odds ratio (OR) 5.788, P<0.001), and an oxygen saturation<88% on room air (OR 5.560, P<0.001), right ventricular dilation (OR 2.480, P=0.006), right ventricular hypokinesis (OR 2.288, P=0.018), require mechanical ventilation for respiratory failure (OR 3.152, P=0.014), and more likely to receive systemic thrombolysis (OR 4.722, P=0.008). On multivariate analysis, syncope on presentation was an independent predictor of a massive APE (OR 2.454, 95% CI 1.109-5.525, P=0.03) after adjusting for patients' age, sex, requirement of antibiotics throughout hospitalization, peak serum creatinine, admission oxygen saturation<88% and admission heart rate>100bpm. There was no difference in mortality in cases with APE with or without syncope (P=0.412). CONCLUSION: Syncope at the onset of pulmonary embolization is a surrogate for submassive and massive APE but is not associated with higher in-hospital mortality.

Bovis Bacillus Calmette-Guerin (BCG) infection induces exosomal miRNA release by human macrophages.

BACKGROUND: Tuberculosis (TB) remains a significant global health concern and its diagnosis is challenging due to the limitations in the specificity and sensitivity of the current diagnostic tests. Exosomes are bioactive 30-100 nm vesicles produced by most cell types and are found in almost all human body fluids. Exosomal microRNAs (miRNAs) can transfer biological information between cells and tissues and may act as potential biomarkers in many diseases. In this pilot study, we assessed the miRNA profile of exosomes released from human monocyte-derived macrophages upon infection with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). METHODS: Human monocytes were obtained from the peripheral blood of three healthy subjects and driven to a monocyte-derived macrophage (MDM) phenotype using standard protocols. MDMs were infected with BCG or left uninfected as control. 72 h post-infection, exosomes were collected from the cell culture medium, RNA was isolated and RNA-seq performed. The raw reads were filtered to eliminate adaptor and primer sequences and the sequences were run against the mature human miRNA sequences available in miRBase. MicroRNAs were identified using an E value <0.01. miRNA network analysis was performed using the DIANA miRNA tool, miRDB and functional KEGG pathway analysis. RESULTS: Infection of MDMs with BCG leads to the release of several exosomal miRNAs. These included miR-1224, -1293, -425, -4467, -4732, -484, -5094, -6848-6849, -4488 and -96 all of which were predicted to target metabolism and energy production-related pathways. CONCLUSIONS: This study provides evidence for the release of specific exosomal miRNAs from BCG-infected MDMs. These exosomal miRNAs reflect host-pathogen interaction and subversion of host metabolic processes following infection.

Mycobacterium aquaticum sp. nov., a rapidly growing species isolated from haemodialysis water.

The characterization of five Iranian isolates, four from hospital haemodialysis water and one from the sputum of a patient, led to the detection of a novel mycobacterium species. The strains were characterized by mucoid colonies developing in 3-5 days at temperatures ranging from 25 to 37 °C. The biochemical test pattern was unremarkable while the HPLC profile of mycolic acids resembled that of Mycobacterium fortuitum. The sequences of three major housekeeping genes (16S rRNA, hsp65 and rpoB) were unique and differed from those of any other mycobacterium. Mycobacterium brisbanense, which is the species that shared the highest 16S rRNA gene sequence similarity (99.03 %), was distinct, as shown by the average nucleotide identity and by the genome to genome distance values (91.05 and 43.10 %, respectively). The strains are thus considered to represent a novel species of the genus Mycobacterium, for which the name Mycobacterium aquaticum sp. nov. is proposed. The type strain is RW6T (=DSM 104277T=CIP111198T).

Mycobacterium persicum sp. nov., a novel species closely related to Mycobacterium kansasii and Mycobacterium gastri.

Four strains isolated in Iran from pulmonary specimens of unrelated patients are proposed as representative of a novel Mycobacterium species. Similarity, at the phenotypic level, with Mycobacterium kansasii is remarkable with the photochromogenic yellow pigmentation of the colonies being the salient feature. They differ, however, genotypically from this species and present unique sequences in 16S rRNA, hsp65 and rpoB genes. The average nucleotide identity and the genome-to-genome distance fully support the status of an independent species. The name proposed for this species is Mycobacterium persicum sp. nov. with AFPC-000227T (=DSM 104278T=CIP 111197T) as the type strain.