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Among all infectious diseases that afflict humans, tuberculosis (TB) remains the deadliest. At present, epidemiologists estimate that one-third of the world population is infected with tubercle bacilli, which is responsible for 8 to 10 million new cases of TB and 3 million deaths annually throughout the world. Approximately 95% of new cases and 98%...
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... In the ara-binogalactan polysaccharide, both galactan main chain and arabinan side branches are designed in a manner that would ensure maximum mobility between sugar residues. The mycolic acid residues are esterified to approximately two-thirds of the non-reducing termini of this highly branched polysaccharide (McNeil & Brennan 1991), as shown in Fig. ...
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Citations
... A group of antibiotics known as rifamycins is effective against several bacteria, notably Mycobacterium tuberculosis, which is the cause of tuberculosis. The most well-known rifamycin is rifampin, which is frequently used to treat illnesses brought on by susceptible bacteria, including tuberculosis (TB) (Ducati et al., 2006). Rifamycins target bacterial RNA polymerase, a crucial enzyme involved in the conversion of bacterial DNA into RNA, as part of their mode of action. ...
Temperature is a critical abiotic factor which determines the microbial diversity in several spheres of earth. Based on the microbial preference for their optimal range of temperature, microorganisms are classified in thermophiles, mesophiles and psychrophiles. However, in an environmental niche with gradient temperature i.e., across hot via warm to cold temperate region with other similar abiotic factors like pH and elemental compositions etc., how the microbial diversity changes with respect to temperature is largely unknown? Similarly, the abundance of various types of temperature-dependent bacteria like thermophiles, thermotolerant, mesophiles, psychro-tolerant and psychrophilic bacteria in a wide range of thermal gradient having antibiotic resistance and ARGs are also unknown. Here in this study, we have found that only specific bacteria tolerant to specific temperature grows optimally in their respective micro-environments. However, there were some commonly shared microbial communities among the mesophiles and psychrophiles but they did not contribute to bacterial abundance. Metagenomic analysis shows the prevalence of Pseudomonadota (Proteobacteria), Bacillota (Firmicutes), Bacteroidota (Bacteroidetes) and these phyla showed a linear increase or decrease in their abundance with respect to temperature. Temperature was the governing factor in shaping the bacterial diversity that was statistically significant by regression models in these microenvironments. Other factors such as pH and various elements, possessed insignificant effect on bacterial diversity. The abundance of mesophilic ARGs were predominant in the distinct thermal microenvironments which suggested that the antibiotic resistance was conferred by mesophiles at large and very few psychrophiles might also play a role in it. Presence of gyrase genes showcased the adaptability of the thermophilic bacteria across the thermal gradients. However, the minimal percentage of reverse gyrase also confirmed that the hot regions were devoid of any hyper-thermophilic microbes. Thermophilic bacteria were found to be devoid of antibiotic resistance. Regression analysis showed the inverse correlation of temperature with antibiotic resistance, i.e., antibiotic resistance decreases with increase in temperature. Antibiotic resistance is maximum at moderate temperatures and usually decreases with the increase and decrease in temperature from the optimum. These studies were carried out in pristine ecosystems with less anthropogenic activities. However, these decisive arguments could be also highlighted by further studying such environments. Furthermore, there is a great scope to perform such studies in contaminated environments that habits such thermal gradients.
... Mycobacterium tuberculosis is known to be the most common strain causing tuberculosis, a potentially dangerous infectious bacterial illness that mostly affect the lungs of infected host. However, it has been observed to also have adverse effect on other regions of the human body [1,2]. Analysis have shown that about one third of the world's population is afflicted with TB, which accounts for over 4000 fatalities per day and thus ranks second only to the human immunodeficiency virus (HIV) as a cause of mortality that may be transmitted [3]. ...
... The electronic properties like HOMO and LUMO energies (E HOMO and E LUMO ), energy gap (ΔE), electron affinity (A), global chemical hardness (η), ionization potential energy (IP), global chemical softness (S), electronegativity index (χ), global chemical electrophilicity index (ω) and chemical potential (μ) were calculated and reported in table? Using equation [1][2][3]32] As such, the result divulged that the highest energy gap (ΔE) of 2.948 eV is associated to Ru-2 molecule while Ru-1 complex is observed to have ΔE of 2.897 eV which affirms high kinetic stability and less reactivity of Ru-2 compound. However, as clearly shown in Fig. 2 and Table 2 the delocalization of electrons from HOMO to LUMO is more prominent in Ru-2 system with higher electron-donating capacity of − 5.053 than Ru-1 compound with nucleophilicity of − 5.043 eV respectively [33]. ...
... The strength of interaction between the donor-acceptor moiety is characterized by the stabilization energy E (2) of the studied complexes. So to say, the more intense the donor-acceptor orbital interaction explicated by the second order perturbation energy E (2) , the more stable the complex might likely be. Correspondingly, the donor-acceptor E (2) (i−j) for nucleophilic (i) and electrophilic (j) moieties are calculated using the equation; ...
This study reports the synthesis, spectroscopic, molecular properties, and in silico biological assessment of ruthenium polypyridyl complexes with a hydroxypyridine ligand, [Ru(bpy)2(N^O)](PF6) (Ru-1) and [Ru(phen)2(N^O)](PF6) (Ru-2). The compounds have been characterized by FT-IR, UV, single crystal X-ray crystallography while molecular electronic properties have been considered within the framework of density functional theory (DFT) computation. The explicit interpretation of the vibrational spectra was assigned by the VEDA4e program. The results obtained from the natural bond analysis explicated that the highest stabilization energy E(2) for the Ru-2 molecule is 343.53 kcal/mol while the Ru-1 compound was observed to possess E(2) energy of 302.42 kcal/mol. The studied Ru-2 compound has been observed to exhibit high gastrointestinal absorption which might restrict the brain-blood barrier or any cytochrome p450 inhibition (1A2, 2C19, 3A4, and 3A4) without infringing any of the Lipniski rules. The molecular docking experiment reveal that the Ru-2 compound binds effectively with 2nv6 tuberculosis receptor with a corresponding binding affinity of − 8.6 kcal/mol obtained for Ru-1 molecule. However, when both compounds were docked with the 5syj receptor, the binding affinity was observed to be − 7.5 and − 6.7 kcal/mol for Ru-2 and Ru-1 respectively, which is comparably higher than the binding score observed for isoniazid standard drug. Ru-2 complex was observed to possess a high energy gap of 2.948 eV with a chemical softness of 0.678 eV, thus suggesting the studied molecule is highly stable and suitable and can be used as a potential anti-tubercular agent. The Uv–vis spectroscopy study divulged that all absorption spectra occurred at the visible region for both molecules respectively, which is in tandem with the obtained experimental λmax.
... These microscopic beads can stay airborne for quite a long time to hours after expectoration [105]. Tuberculosis spreads through the air, usually infecting patients through their lungs [106]. White platelets consume the Mycobacterium tuberculosis, yet won't be separated by them. ...
Background
In terms of death rates, occurrence, costs, and prevalence, respiratory tract diseases, which include minor issues like the common cold and life-threatening ones like bacterial pneumonia, lung cancers, and tuberculosis, are extremely significant. People have been worried about their health for a long time because of respiratory diseases. Old-style medication has tended to these diseases; however, the accumulation of information produced by elective methodologies, among which medication assumes a significant role, is insignificant. Phytotherapy has consistently given proficient solutions for constant and moderate wellbeing inconveniences and, occasionally, for intense and serious problems. Alleviating the aggravated nasal sections and aviation routes was a shared need in antiquated societies. In this study, we conducted a systematic literature review to gain evidence about herbal products and their phytoconstituents that play a role in respiratory illness. We also predicted the physicochemical properties of various phytoconstituents from therapeutic plants employed to cure respiratory ailments (such as asthma, COPD, cough, tuberculosis, etc.).
Objectives
The main objective of this critical study is to explore phytotherapy-based molecules for respiratory illnesses. The physicochemical properties of already isolated compounds have been evaluated to screen for the drug-like behavior of phytoconstituents.
Methodology
A wide variety of literature has been collected from PubMed, Google Scholar, Medline, and other scientific databases. After an exhaustive review, the chemical structures of phytoconstituents responsible for curing respiratory illness were sketched in ChemDraw Ultra 8.0, and these structures have been taken for further analysis of the physicochemical properties of these phytoconstituents. The crucial parameters of phytoconstituents' physicochemical properties were analyzed using the pkCSM webserver.
Result
The results suggest that a variety of phytoconstituents have the potential to treat respiratory illnesses, and the physicochemical parameters reveal that 65 compounds out of 130 screened compounds exhibit Lipinski's rule of five and Veber's rule, while others don't obey these rules. Compounds with optimal physicochemical properties could be promising candidates for emerging respiratory illness treatments.
Conclusion
This critical review highlights the possible therapeutic potential of plant-based medicine to cure respiratory illnesses. The finding shows that a wide range of alkaloids, glycosides, terpenoids, and flavonoids isolated from different herbs may be able to treat respiratory problems. More research is needed to find out the IC50 and MIC values of these compounds against respiratory pathogens like S. pneumoniae and M. tuberculosis.
... Early diagnosis and adequate treatment are essential for the effectiveness of public programs to control the disease, which aim to cure the patient and prevent the transmission of the bacillus to the community. However, non-adherence to the treatment regimen, i.e., abandonment due to long-duration or adverse effects of antibiotics, are major risk factors for the development of resistance in tuberculosis [2,3]. ...
Tuberculosis remains a major public health problem and one of the top ten causes of death worldwide. The alarming increase in multidrug-resistant and extensively resistant variants (MDR, pre-XDR, and XDR) makes the disease more difficult to treat and control. New drugs that act against MDR/XDR strains are needed for programs to contain this major epidemic. The present study aimed to evaluate new compounds related to dihydro-sphingosine and ethambutol against sensitive and pre-XDR Mycobacterium strains, as well as to characterize the pharmacological activity through in vitro and in silico approaches in mmpL3 protein. Of the 48 compounds analyzed, 11 demonstrated good to moderate activity on sensitive and MDR Mycobacterium tuberculosis (Mtb), with a Minimum Inhibitory Concentration (MIC) ranging from 1.5 to 8 μM. They presented 2 to 14 times greater potency of activity when compared to ethambutol in pre-XDR strain, and demonstrated a selectivity index varying between 2.21 and 82.17. The substance 12b when combined with rifampicin, showed a synergistic effect (FICI = 0.5) on sensitive and MDR Mtb. It has also been shown to have a concentration-dependent intracellular bactericidal effect, and a time-dependent bactericidal effect in M. smegmatis and pre-XDR M. tuberculosis. The binding mode of the compounds in its cavity was identified through molecular docking and using a predicted structural model of mmpL3. Finally, we observed by transmission electron microscopy the induction of damage to the cell wall integrity of M. tuberculosis treated with the substance 12b. With these findings, we demonstrate the potential of a 2-aminoalkanol derivative to be a prototype substance and candidate for further optimization of molecular structure and anti-tubercular activity in preclinical studies.
... Tuberculosis (TB) is a communicable disease caused by the bacteria Mycobacterium tuberculosis [1,2]. TB is a serious issue in low-income, developing East African nations, accounting for 98% of fatalities and 95% of newly diagnosed cases [3,4]. However, the incidence of TB is increasing in the industrialised world as a result of higher HIV infection rates, an increase in immunosuppressive medications, and greater immigration from low-income developing countries [5]. ...
Bowel obstruction caused by intestinal TB is more common in emerging, low-income countries in East Africa. In developing countries, intestinal TB, which accounts for 2% of all TB cases globally, is a serious issue. For simple cases of intestinal TB, medical anti-TB therapy is employed; nevertheless, surgery is necessary for complications such intestine obstruction and perforations that result in peritonitis. This case report's goal is to alert surgeons to the possibility that TB patients may present with abdominal TB sequelae such small intestinal obstruction. a 45-year-old man who had been experiencing broad intermittent abdominal pain and sporadic vomiting for two months. Two minor bowel strictures were found in the ileocaecal area during laparotomy. He underwent a limited right hemicolectomy, an ileocolic anastomosis, and was postoperatively placed on anti-TB medicine. Following surgery, the histology revealed intestinal TB with signs of TB lymphadenitis and persistent granulomatous inflammation. Bowel blockage caused by tuberculosis is very common in our environment and raises mortality and morbidity rates. Abdominal TB frequently becomes problematic since the vast majority of patients arrive late. When patients come with small bowel obstruction, surgeons should have a high clinical suspicion level and, if a diagnosis has been made, the patient should be quickly assessed for anti-TB medication and surgery.
... Tuberculosis (TB) is a major health problem globally and is a communicable disease caused by mycobacterium tuberculosis [1,2]. In developing low-income countries in East Africa, TB is a significant problem with 98% of deaths and 95% new cases diagnosed [3,4]. However, in the developed world the incidence of TB is on the rise due to an increased prevalence of HIV infection, an increase in immunosuppressive treatment, and increased immigration from developing low-income countries [5]. ...
Introduction: In developing low-income countries in East Africa bowel obstruction due to intestinal TB is more prevalent. Globally intestinal TB accounts for 2% of all TB cases and in developing countries is a significant problem. Medical anti-TB treatment is used to manage uncomplicated cases of intestinal TB however surgery is required for complications such as bowel obstruction and perforations leading to peritonitis. The purpose of this case report is to make surgeons aware that TB patients may present with complications of abdominal TB such as small bowel obstruction.
... Despite the availability of specific chemotherapy since the 1950s has contributed to drastically reducing the number of cases (1), the WHO Global Tuberculosis Report of 2021 still defines tuberculosis (TB) as one of the top causes of death from a single infectious agent worldwide (ranking above HIV/AIDS) (2). The main reasons for the "re-emergence" of TB are the increased onset of socio-economic disparities related to migratory flow from developing countries and the increase in immunosuppressive diseases or, anyhow, diseases requiring immunosuppressive treatments (3). ...
Background
It is still unclear if low lymphocyte levels are directly related to immunological modifications induced by the TB infection or if they depend on the general pre-existing health impairment of affected patients. Our aim was to detect eventual differences in the immunological status of patients with pulmonary TB compared to an age and sex-matched group of hospitalized patients with other bacterial community-acquired pneumonia (CAP). In addition, we tried to assess an association between alterations in the peripheral lymphocyte subsets and the development of different CT patterns of active TB and to discover differences in the immunological status and in the radiological patterns of TB presentation between patients of different geographic proveniences.
Methods
This observational study included 48 patients with TB and 48 sex- and age-matched patients affected by other bacterial CAP. The presence of HIV/AIDS, other immunocompromising conditions, and confounding chronic pulmonary comorbidities was excluded. Flow cytometry was performed on all the enrolled subjects at admission, before starting the appropriate antibiotic therapy. Patients with TB also underwent a computed tomography (CT) scan.
Results
Patients with TB showed a decrease in the absolute count of all the lymphocyte subsets compared to the CAP group. Only the reduction in the percentage of CD4+ T-lymphocytes was significant, while the percentage of CD8+ T-lymphocytes was significantly increased. Patients presenting exudative forms with atypical locations of TB showed a significant reduction in the absolute count and percentage of CD19+ B-lymphocytes compared to those affected by productive TB forms with the typical location. Despite being younger, our black Sub-Saharan Africans showed a significant reduction in the CD4+ T-lymphocytes compartment and a higher prevalence of atypical and exudative forms of TB compared with white Europeans.
Conclusion
Tuberculosis itself may alter peripheral blood lymphocyte subsets compared to other CAP. An impaired CD19+ B-lymphocyte compartment may result in an abnormal exudative response in atypical locations and a suboptimal bacterial control. Other constitutive or environmental causes may influence immunological differences found in patients with TB, particularly in case of different geographic origins. Anyhow, flow cytometry may be of great value in evaluating the immune function of these patients.
... The significance of epidemiological, health and socio-economic aspects of this disease determine the urgent need for new drugs. Among these issues are increasing bacterial resistance to drugs, in particular multidrug-and extensively drug-resistant M. tuberculosis, a coincidence of tuberculosis with infection with human im-munodeficiency virus (HIV), dormant tuberculosis, and unusual infections with mycobacteria [155]. ...
Background
Human infectious diseases caused by bacteria are a worldwide health problem due to the increased resistance of these microorganisms to conventional antibiotics. For this reason, the identification of novel molecular targets and the discovery of new antibacterial compounds is urgently required. Metalo-aminopeptidases are promising targets in bacterial infections. They participate in crucial processes for bacterial growth and pathogenesis, such as protein and peptide degradation to supply amino acids, protein processing, access to host tissues, cysteine supply for redox control, transcriptional regulation, site-specific DNA recombination, and hydrogen sulfide production. Although several of these enzymes are not essential, they are required for virulence and maximal growth in conditions of nutrient limitation and high temperatures.
Objective
In this review, we describe the structural, functional and kinetic properties of some examples of bacterial metalo-aminopeptidases, in the context of their use as antibacterial targets. In addition, we present some inhibitors reported for these enzymes.
Conclusion
It is necessary a meticulous work to validate these peptidases as good/bad targets and to identify inhibitors with a potential therapeutic use.
... The activity against mono-resistant strains is particularly significant due to the fact that any large bacterial population may naturally contain mutants that are resistant to single drugs. For M. tuberculosis, the resistance against rifampicin and isoniazid is developing relatively fast so the extra-cellular population of bacilli will include mono-resistant organisms [45]. All so far corroborated data show that out of the 17 compounds that showed antitubercular activity, 6 were highly active on the H37Rv wild strain, out of which 4 also emerged as moderately active compounds on the three antibiotic resistant strains. ...
Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against Mycobacterium tuberculosis, mono-resistant MTB strains, and nontuberculous strains Mycobacterium abscessus and Mycobacterium avium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound 7), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains. Molecular docking corroborated with a machine learning drug-drug similarity algorithm revealed that azepano-triterpenoids have a rifampicin-like antitubercular activity, with compound 7 scoring the highest as a potential M. tuberculosis RNAP potential inhibitor. FIC testing demonstrated an additive effect of compound 7 when combined with rifampin, isoniazid and ethambutol. Most compounds were highly active against M. avium with compound 14 recording the same MIC value as the control rifampicin (0.0625 µM). The antitubercular ex vivo effectiveness of the tested compounds on THP-1 infected macrophages is correlated with their increased cell permeability. The tested triterpenoids also exhibit low cytotoxicity and do not induce antibacterial resistance in MTB strains.
... No plasmids or transposable elements (horizontal gene transfer) are involved in this process. Individual nucleotide changes (point mutations) confer resistance to single drugs, and the stepwise accumulation of these mutations leads to MDR TB. drug resistance strains emerge when chemotherapy is intermittent or otherwise inadequate (Ducati, 2006;Zhang and Yew, 2009). ...
