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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 53568

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Prof. Dr. Vishwanath Venketaraman

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Guest Editor

Microbiology/Immunology Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA
Interests: mycobacterial diseases; tuberculosis; host immune responses; pathogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mycobacterial infections continue to cause significant mortality and morbidity in humans worldwide, especially in those individuals with compromised immune system. With growing numbers of individuals with diabetes and HIV, and the emergence of drug-resistant strains of mycobacteria, there is an urgent need to develop novel therapeutic strategies to combat mycobacterial infections. This Special Issue will include original articles pertaining to the most recent advances in the discovery of antimicrobial peptides, new compounds, and repurposed drugs that have antimycobacterial effects. We welcome preclinical and clinical research studies that undertake mechanistic approaches to better understand the mechanism of action of novel therapeutic compounds, host-pathogen interactions, and pathogenesis in the context of mycobacterial infection. Review articles and commentaries on the current breakthroughs in this field are highly welcomed.

Prof. Dr. Vishwanath Venketaraman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Mycobacterial diseases
Adjunctive therapy
Immune-enhancing agents
Antimycobacterial compounds
Host-directed therapies
Pathogenesis
Modulation of host immune responses

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 188 KiB

Open AccessEditorial

Recent Advances in Mycobacterial Research

by Vishwanath Venketaraman

J. Clin. Med. 2020, 9(8), 2650; https://doi.org/10.3390/jcm9082650 - 14 Aug 2020

Cited by 1 | Viewed by 1980

Abstract

Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease that is responsible for causing significant morbidity and death [...] Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

Research

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11 pages, 1946 KiB

Open AccessArticle

Long-Term Clinical and Multimodal Imaging Findings in Patients with Disseminated Mycobacterium Chimaera Infection

by Sandrine Anne Zweifel, Maximilian Robert Justus Wiest, Mario Damiano Toro, Pascal Hasler, Peter Maloca, Barbara Hasse, Nina Khanna and Robert Rejdak

J. Clin. Med. 2021, 10(18), 4178; https://doi.org/10.3390/jcm10184178 - 16 Sep 2021

Cited by 7 | Viewed by 2338

Abstract

Background: To analyze long-term ophthalmic clinical and multimodal imaging findings of disseminated Mycobacterium (M.) chimaera infection after cardiothoracic surgery among the Swiss Cohort. Methods: Systemic and multimodal ophthalmic imaging and clinical findings including rate of recurrence were reviewed and correlated to a previously proposed classification system of choroidal lesions and classification of ocular disease. Main Outcomes Measures: long-term clinical and multimodal ocular imaging findings of M. chimaera. Results: Twelve patients suffering from systemic infection from M. chimaera were included. Mean age at the first ophthalmic examination was 59 years (range from 48 to 66 years). Mean duration of the follow-up was 22.63 ± 17.8 months. All patients presented with bilateral chorioretinal lesions at baseline; 5 patients had additional signs, including optic disc swelling (2), choroidal neovascularization (1), retinal neovascularization (1) and cilioretinal vascular occlusion (1). Four recurrence events after discontinuation or adjustment of the antibiotic treatment were observed. Progressive choroiditis was seen in 5 patients under treatment, 4 of them deceased. Conclusions: Expertise from ophthalmologists is not only relevant but also critical for the assessment of the adverse drug effect of antimycobacterial treatment along with monitoring therapeutic response and identifying recurrences. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

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12 pages, 460 KiB

Open AccessArticle

The Accuracy of Emergency Physicians’ Suspicions of Active Pulmonary Tuberculosis

by Shiang-Jin Chen, Chun-Yu Lin, Tzu-Ling Huang, Ying-Chi Hsu and Kuan-Ting Liu

J. Clin. Med. 2021, 10(4), 860; https://doi.org/10.3390/jcm10040860 - 19 Feb 2021

Cited by 2 | Viewed by 2539

Abstract

Objective: To investigate factors associated with recognition and delayed isolation of pulmonary tuberculosis (PTB). Background: Precise identification of PTB in the emergency department (ED) remains challenging. Methods: Retrospectively reviewed PTB suspects admitted via the ED were divided into three groups based on the acid-fast bacilli culture report and whether they were isolated initially in the ED or general ward. Factors related to recognition and delayed isolation were statistically compared. Results: Only 24.94% (100/401) of PTB suspects were truly active PTB and 33.77% (51/151) of active PTB were unrecognized in the ED. Weight loss (p = 0.022), absence of dyspnea (p = 0.021), and left upper lobe field (p = 0.024) lesions on chest radiographs were related to truly active PTB. Malignancy (p = 0.015), chronic kidney disease (p = 0.047), absence of a history of PTB (p = 0.013), and lack of right upper lung (p ≤ 0.001) and left upper lung (p = 0.020) lesions were associated with PTB being missed in the ED. Conclusions: Weight loss, absence of dyspnea, and left upper lobe field lesions on chest radiographs were related to truly active PTB. Malignancy, chronic kidney disease, absence of a history of PTB, and absence of right and/or left upper lung lesions on chest radiography were associated with isolation delay. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

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7 pages, 230 KiB

Open AccessArticle

Molecular Detection of Mycobacterium tuberculosis in Oral Mucosa from Patients with Presumptive Tuberculosis

by Barbara Molina-Moya, Nelly Ciobanu, Marta Hernandez, Cristina Prat-Aymerich, Valeriu Crudu, Emily R. Adams, Alexandru Codreanu, Derek J. Sloan, Luis E. Cuevas and Jose Dominguez

J. Clin. Med. 2020, 9(12), 4124; https://doi.org/10.3390/jcm9124124 - 21 Dec 2020

Cited by 17 | Viewed by 3478

Abstract

Tuberculosis (TB) diagnosis is increasingly based on the detection of Mycobacterium tuberculosis complex (MTBC) DNA in sputum using molecular diagnostic tests as the first test for diagnosis. However, sputum can be difficult to obtain in children, patients without productive cough, and the elderly and approaches testing non-sputum samples are needed. We evaluated whether TB can be detected from the oral mucosa of patients with TB. Adults with presumptive TB were examined using culture, Xpert MTB/RIF, smear microscopy and X-Rays. Oral mucosa swabs collected on PrimeStore-MTM, stored at room temperature if tested within 30 days or at −20 °C if examined at a later time. RT-PCR was performed to detect M. tuberculosis DNA. Eighty patients had bacteriologically-confirmed TB, 34 had bacteriologically-negative TB (negative tests but abnormal X-rays) and 152 were considered not to have TB (not TB). Oral swabs RT-PCR were positive in 29/80 (36.3%) bacteriologically-confirmed, 9/34 (26.5%) bacteriologically-negative and 29/152 (19.1%) not TB. The yield varied among samples stored for less and more than 30 days (p = 0.013) from 61% (11/18) and 29% (18/62) among bacteriologically confirmed, and 30.8% (4/13) and 23.8% (5/21) among bacteriologically-negative participants. Among not TB patients, the specificity was 80.9% (123/152), being 78.3% (18/23) among samples stored less than 30 days and 81.4% (105/129) among samples stored for more than 30 days (p = 0.46). The detection of M. tuberculosis in oral mucosa samples is feasible, but storage conditions may affect the yield. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

14 pages, 2091 KiB

Open AccessArticle

Antimycobacterial Effects of Everolimus in a Human Granuloma Model

by David Ashley, Joshua Hernandez, Ruoqiong Cao, Kimberly To, Aram Yegiazaryan, Rachel Abrahem, Timothy Nguyen, James Owens, Maria Lambros, Selvakumar Subbian and Vishwanath Venketaraman

J. Clin. Med. 2020, 9(7), 2043; https://doi.org/10.3390/jcm9072043 - 29 Jun 2020

Cited by 26 | Viewed by 3669

Abstract

Mycobacterium tuberculosis (M. tb) has been historically and is currently a threat to global public health. First-line antibiotics have been effective but proven to be burdensome as they have many potential adverse side effects. There has been a recent increase in the number of active tuberculosis (TB) cases due to a prevalence of multidrug and extensively drug-resistant strains of M. tb, and an increasing number of highly susceptible people such as those with Type 2 Diabetes (T2DM) and human immunodeficiency virus (HIV) infection. Multidrug-resistant M. tb infection (MDR-TB) is challenging to treat with existing therapeutics, so novel therapeutics and treatment strategies must be developed. Host-Directed Therapy (HDT) has been a potential target mechanism for effective clearance of infection. Host cell autophagy plays an essential role in antibacterial defense. The mammalian target of rapamycin (mTOR) has been negatively correlated with autophagy induction. Everolimus is an mTOR inhibitor that induces autophagy, but with higher water solubility. Therefore, targeting the mTOR pathway has the potential to develop novel and more effective combination drug therapy for TB. This study tested the effect of everolimus, alone and in combination with current first-line antibiotics (isoniazid and pyrazinamide), on the inhibition of M. tb inside in vitro human granulomas. We found that M. tb-infected in vitro granulomas treated with everolimus alone resulted in significantly decreased M. tb burden compared to similar granulomas in the control group. Cells treated with everolimus doses of either 1 nM or 2 nM in conjunction with pyrazinamide (PZA) produced a significant reduction in intracellular M. tb burden. Treatment groups that received everolimus alone in either 1 nM or 2 nM doses experienced a significant reduction in oxidative stress. Additionally, samples treated with 2 nM everolimus alone were observed to have significantly higher levels of autophagy and mTOR inhibition as well. Results from this study indicate that everolimus is efficacious in controlling M. tb infection in the granulomas and has additive effects when combined with the anti-TB drugs, isoniazid and pyrazinamide. This study has shown that everolimus is a promising host-directed therapeutic in the context of in vitro granuloma M. tb infection. Further study is warranted to better characterize these effects. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

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Review

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23 pages, 1356 KiB

Open AccessReview

Pathogenesis of Human Immunodeficiency Virus-Mycobacterium tuberculosis Co-Infection

by Kevin Wong, James Nguyen, Lillie Blair, Marina Banjanin, Bunraj Grewal, Shane Bowman, Hailey Boyd, Grant Gerstner, Hyun Jun Cho, David Panfilov, Cho Ki Tam, Delaney Aguilar and Vishwanath Venketaraman

J. Clin. Med. 2020, 9(11), 3575; https://doi.org/10.3390/jcm9113575 - 6 Nov 2020

Cited by 26 | Viewed by 8226

Abstract

Given that infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death amongst individuals living with HIV, understanding the complex mechanisms by which Mtb exacerbates HIV infection may lead to improved treatment options or adjuvant therapies. While it is well-understood how HIV compromises the immune system and leaves the host vulnerable to opportunistic infections such as Mtb, less is known about the interplay of disease once active Mtb is established. This review explores how glutathione (GSH) depletion, T cell exhaustion, granuloma formation, and TNF-α upregulation, as a result of Mtb infection, leads to an increase in HIV disease severity. This review also examines the difficulties of treating coinfected patients and suggests further research on the clinical use of GSH supplementation. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

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19 pages, 249 KiB

Open AccessReview

Analysis of Tuberculosis Meningitis Pathogenesis, Diagnosis, and Treatment

by Aysha Arshad, Sujay Dayal, Raj Gadhe, Ajinkya Mawley, Kevin Shin, Daniel Tellez, Phong Phan and Vishwanath Venketaraman

J. Clin. Med. 2020, 9(9), 2962; https://doi.org/10.3390/jcm9092962 - 14 Sep 2020

Cited by 20 | Viewed by 8562

Abstract

Tuberculosis (TB) is the most prevalent infectious disease in the world. In recent years there has been a significant increase in the incidence of TB due to the emergence of multidrug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) and the increased numbers of highly susceptible immuno-compromised individuals. Central nervous system TB, includes TB meningitis (TBM-the most common presentation), intracranial tuberculomas, and spinal tuberculous arachnoiditis. Individuals with TBM have an initial phase of malaise, headache, fever, or personality change, followed by protracted headache, stroke, meningismus, vomiting, confusion, and focal neurologic findings in two to three weeks. If untreated, mental status deteriorates into stupor or coma. Delay in the treatment of TBM results in, either death or substantial neurological morbidity. This review provides latest developments in the biomedical research on TB meningitis mainly in the areas of host immune responses, pathogenesis, diagnosis, and treatment of this disease. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

15 pages, 1243 KiB

Open AccessReview

Understanding the Relationship between Glutathione, TGF-β, and Vitamin D in Combating Mycobacterium tuberculosis Infections

by Mohkam Singh, Charles Vaughn, Kayvan Sasaninia, Christopher Yeh, Devanshi Mehta, Ibrahim Khieran and Vishwanath Venketaraman

J. Clin. Med. 2020, 9(9), 2757; https://doi.org/10.3390/jcm9092757 - 26 Aug 2020

Cited by 7 | Viewed by 4653

Abstract

Tuberculosis (TB) remains a pervasive global health threat. A significant proportion of the world’s population that is affected by latent tuberculosis infection (LTBI) is at risk for reactivation and subsequent transmission to close contacts. Despite sustained efforts in eradication, the rise of multidrug-resistant strains of Mycobacteriumtuberculosis (M. tb) has rendered traditional antibiotic therapy less effective at mitigating the morbidity and mortality of the disease. Management of TB is further complicated by medications with various off-target effects and poor compliance. Immunocompromised patients are the most at-risk in reactivation of a LTBI, due to impairment in effector immune responses. Our laboratory has previously reported that individuals suffering from Type 2 Diabetes Mellitus (T2DM) and HIV exhibited compromised levels of the antioxidant glutathione (GSH). Restoring the levels of GSH resulted in improved control of M. tb infection. The goal of this review is to provide insights on the diverse roles of TGF- β and vitamin D in altering the levels of GSH, granuloma formation, and clearance of M. tb infection. We propose that these pathways represent a potential avenue for future investigation and development of new TB treatment modalities. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

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15 pages, 2657 KiB

Open AccessFeature PaperReview

The Role of Dendritic Cells in TB and HIV Infection

by Rachel Abrahem, Emerald Chiang, Joseph Haquang, Amy Nham, Yu-Sam Ting and Vishwanath Venketaraman

J. Clin. Med. 2020, 9(8), 2661; https://doi.org/10.3390/jcm9082661 - 17 Aug 2020

Cited by 12 | Viewed by 5088

Abstract

Dendritic cells are the principal antigen-presenting cells (APCs) in the host defense mechanism. An altered dendritic cell response increases the risk of susceptibility of infections, such as Mycobacterium tuberculosis (M. tb), and the survival of the human immunodeficiency virus (HIV). The altered response of dendritic cells leads to decreased activity of T-helper-1 (Th1), Th2, Regulatory T cells (Tregs), and Th17 cells in tuberculosis (TB) infections due to a diminishment of cytokine release from these APCs, while HIV infection leads to DC maturation, allowing DCs to migrate to lymph nodes and the sub-mucosa where they then transfer HIV to CD4 T cells, although there is controversy around this topic. Increases in the levels of the antioxidant glutathione (GSH) plays a critical role in maintaining dendritic cell redox homeostasis, leading to an adequate immune response with sufficient cytokine release and a subsequent robust immune response. Thus, an understanding of the intricate pathways involved in the dendritic cell response are needed to prevent co-infections and co-morbidities in individuals with TB and HIV. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

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24 pages, 402 KiB

Open AccessReview

General Overview of Nontuberculous Mycobacteria Opportunistic Pathogens: Mycobacterium avium and Mycobacterium abscessus

by Kimberly To, Ruoqiong Cao, Aram Yegiazaryan, James Owens and Vishwanath Venketaraman

J. Clin. Med. 2020, 9(8), 2541; https://doi.org/10.3390/jcm9082541 - 6 Aug 2020

Cited by 138 | Viewed by 11281

Abstract

Nontuberculous mycobacteria (NTM) are emerging human pathogens, causing a wide range of clinical diseases affecting individuals who are immunocompromised and who have underlying health conditions. NTM are ubiquitous in the environment, with certain species causing opportunistic infection in humans, including Mycobacterium avium and Mycobacterium abscessus. The incidence and prevalence of NTM infections are rising globally, especially in developed countries with declining incidence rates of M. tuberculosis infection. Mycobacterium avium, a slow-growing mycobacterium, is associated with Mycobacterium avium complex (MAC) infections that can cause chronic pulmonary disease, disseminated disease, as well as lymphadenitis. M. abscessus infections are considered one of the most antibiotic-resistant mycobacteria and are associated with pulmonary disease, especially cystic fibrosis, as well as contaminated traumatic skin wounds, postsurgical soft tissue infections, and healthcare-associated infections (HAI). Clinical manifestations of diseases depend on the interaction of the host’s immune response and the specific mycobacterial species. This review will give a general overview of the general characteristics, vulnerable populations most at risk, pathogenesis, treatment, and prevention for infections caused by Mycobacterium avium, in the context of MAC, and M. abscessus. Full article

(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)

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