Targeting endogenous gaseous signaling molecules as novel host-directed therapies against tuberculosis infection

Gautam, Kamini; Negi, Sheetal; Saini, Vikram

doi:10.1080/10715762.2021.1892091

Cited by 6 publications

(3 citation statements)

References 136 publications

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“…This study used two opportunistic pathogens, namely Staphylococcus aureus (MTCC # 1430) and Acinetobacter baumannii (MTCC # 1425) to evaluate the impact of treatment on macrophage health and infection [88]. Briefly, S. aureus and A. baumannii were cultured on LB broth at 37 °C overnight under shaking at 180 rpm [89].…”

Section: Bacterial Strain and Culture Conditionmentioning

confidence: 99%

Amoxicillin modulates gut microbiota to improve short-term high-fat diet induced pathophysiology in mice

et al. 2022

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Background A high-fat diet (HFD) induced perturbation of gut microbiota is a major contributory factor to promote the pathophysiology of HFD-associated metabolic syndrome. The HFD could also increase the susceptibility to the microbial infections warranting the use of antibiotics which are independently capable of impacting both gut microbiota and metabolic syndrome. Further, the usage of antibiotics in individuals consuming HFD can impact mitochondrial function that can be associated with an elevated risk of chronic conditions like inflammatory bowel disease (IBD). Despite this high propensity to infections in individuals on HFD, the link between duration of HFD and antibiotic treatment, and its impact on diversity of the gut microbiome and features of metabolic syndrome is not well established. In this study, we have addressed these knowledge gaps by examining how the gut microbiota profile changes in HFD-fed mice receiving antibiotic intervention in the form of amoxicillin. We also determine whether antibiotic treatment in HFD-fed mice may adversely impact the ability of immune cells to clear microbial infections. Methods and Results We have subjected mice to HFD and chow diet (CD) for 3 weeks, and a subset of these mice on both diets received antibiotic intervention in the form of amoxicillin in the 3rd week. Body weight and food intake were recorded for 3 weeks. After 21 days, all animals were weighted and sacrificed. Subsequently, these animals were evaluated for basic haemato-biochemical and histopathological attributes. We used 16S rRNA sequencing followed by bioinformatics analysis to determine changes in gut microbiota in these mice. We observed that a HFD, even for a short-duration, could successfully induce the partial pathophysiology typical of a metabolic syndrome, and substantially modulated the gut microbiota in mice. The short course of amoxicillin treatment to HFD-fed mice resulted in beneficial effects by significantly reducing fasting blood glucose and skewing the number of thrombocytes towards a normal range. Remarkably, we observed a significant remodelling of gut microbiota in amoxicillin-treated HFD-fed mice. Importantly, some gut microbes associated with improved insulin sensitivity and recovery from metabolic syndrome only appeared in amoxicillin-treated HFD-fed mice reinforcing the beneficial effects of antibiotic treatment in the HFD-associated metabolic syndrome. Moreover, we also observed the presence of gut-microbiota unique to amoxicillin-treated HFD-fed mice that are also known to improve the pathophysiology associated with metabolic syndrome. However, both CD-fed as well as HFD-fed mice receiving antibiotics showed an increase in intestinal pathogens as is typically observed for antibiotic treatment. Importantly though, infection studies with S. aureus and A. baumannii, revealed that macrophages isolated from amoxicillin-treated HFD-fed mice are comparable to those isolated from mice receiving only HFD or CD in terms of susceptibility, and progression of microbial infection. This finding clearly indicated that amoxicillin treatment does not introduce any additional deficits in the ability of macrophages to combat microbial infections. Conclusions Our results showed that amoxicillin treatment in HFD-fed mice exert a beneficial influence on the pathophysiological attributes of metabolic syndrome which correlates with a significant remodelling of gut microbiota. A novel observation was the increase in microbes known to improve insulin sensitivity following amoxicillin treatment during short-term intake of HFD. Even though there is a minor increase in gut-resistant intestinal pathogens in amoxicillin-treated groups, there is no adverse impact on macrophages with respect to their susceptibility and ability to control infections. Taken together, this study provides a proof of principle for the exploration of amoxicillin treatment as a potential therapy in the people affected with metabolic syndrome.

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Section: Bacterial Strain and Culture Conditionmentioning

confidence: 99%

Amoxicillin modulates gut microbiota to improve short-term high-fat diet induced pathophysiology in mice

et al. 2022

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“…In addition, the application of the NMDA receptor blocker AP-5 blocked endogenous H 2 S-induced LTP, thus suggesting that the occurrence of endogenous H 2 S-induced LTP is NMDA receptor dependent. Found that the administration of a certain concentration of NaHS (a donor of H 2 S) increased the amount of cyclic adenosine monophosphate (cAMP) in neuronal cells and glial cells in vitro, and thus, endogenous H 2 S-induced LTP was dependent on cAMP acting as a second messenger in the relevant cells (37,38).…”

Section: H 2 S Modulates Hippocampal Longduration Enhancementmentioning

confidence: 99%

Endocrine effects of three common gas signaling molecules in humans: A literature review

Luo

Suguro

et al. 2022

Front. Endocrinol.

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Gases such as hydrogen sulfide, nitric oxide and sulfur dioxide have important regulatory effects on the endocrine and physiological processes of the body and are collectively referred to as “gas signaling molecules”. These gas signaling molecules are also closely related to Alzheimer’s disease, the inflammatory response and depression. In this paper, we introduce the production and metabolic pathways of NO, H2S and SO2 in living organisms and review the regulatory functions of gas signaling molecules in the endocrine system and their mechanisms in relation to their clinical applications. This work will provide a basis for finding targets for intervention and establishing novel prevention and treatment strategies for related diseases.

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“…Tuberculosis (TB) is a pulmonary infectious disease caused by Mycobacterium tuberculosis that seriously affects human health and is one of the most critical public health problems of the world (1,2). According to the report of the World Health Organization, 10.4 million new TB patients were diagnosed globally in 2016.…”

Section: Introductionmentioning

confidence: 99%

Application Value of BALF mNGS for Screening Patients With Mycobacterium Tuberculosis Infection in General Hospitals

Wang

Zhou

Cao

et al. 2022

Preprint

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BackgroundTo evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in patients with Mycobacterium tuberculosis infection.MethodsPatients hospitalized for pneumonia in the Department of Pulmonary and Critical Care Medicine of Wuhan Central Hospital from January to June 2021 were enrolled in the study. Patients were examined by mNGS and divided into two groups according to the M. tuberculosis infection. We compared the clinical indicators of infected patients of both groups. All patients in the M. tuberculosis infection group underwent bronchoalveolar lavage (BAL). Different detection methods were used to detect pathogenic bacteria. ResultsA total of 111 patients agreed to undergo mNGS. Of these, 15 were eventually enrolled in the study group. We found that patients with decreased white blood cells had a higher risk of infection with M. tuberculosis than those infected with other pathogens (OR=0.807, 95%CI: 0.672–0.969, P=0.022). We also found that mNGS had a higher positive rate of M. tuberculosis infection detection than traditional detection methods. The positive detection rates of TB-DNA-PCR, Xpert MTB, and T-SPOT. TB were 69.23%, 83.33%, 77.77%, respectively.ConclusionsBALF mNGS assay could quickly and effectively detect M. tuberculosis complex in patients with pulmonary infection in a general hospital setting.

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Targeting endogenous gaseous signaling molecules as novel host-directed therapies against tuberculosis infection

Cited by 6 publications

References 136 publications

Amoxicillin modulates gut microbiota to improve short-term high-fat diet induced pathophysiology in mice

Amoxicillin modulates gut microbiota to improve short-term high-fat diet induced pathophysiology in mice

Endocrine effects of three common gas signaling molecules in humans: A literature review

Application Value of BALF mNGS for Screening Patients With Mycobacterium Tuberculosis Infection in General Hospitals

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