Introduction: Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) remains a global health concern because of the development of drug resistance. The adaptability of MTB in response to a variety of environmental stresses is a crucial strategy that supports their survival and evades host defense mechanisms. Stress regulates gene expression, particularly virulence genes, leading to the development of drug tolerance. Mannose-capped lipoarabinomannan (ManLAM) is a critical component of the cell wall, functions as a virulence factor and influences host defense mechanisms.Purpose: This study focuses on the effect of isoniazid (INH) stress on the regulation of ManLAM-related genes, to improve our understanding of virulence and drug resistance development in MTB. Materials and Methods: MTB with distinct drug resistance profiles were used for gene expression analysis. Multiplex-real time PCR assay was performed to monitor stress-related genes (hspX, tgs1, and sigE). The expression levels of ManLAM-related genes (pimB, mptA, mptC, dprE1, dprE2, and embC) were quantified by qRT-PCR. Sequence analysis of drug resistance-associated genes (inhA, katG, and rpoB) and ManLAM-related genes were performed to establish a correlation between genetic variation and gene expression. Results: INH treatment activates the stress response mechanism in MTB, resulting in a distinct gene expression pattern between drug resistance and drug-sensitive TB. In response to INH, hspX was up-regulated in RIF-R and MDR. tgs1 was strongly up-regulated in MDR, whereas sigE was dramatically up-regulated in the drug-sensitive TB. Interestingly, ManLAM-related genes were most upregulated in drug resistance, notably MDR (pimB, mptA, dprE1, and embC), implying a role for drug resistance and adaptability of MTB via ManLAM modulation. Conclusion:This study establishes a relationship between the antibiotic stress response mechanism and the expression of ManLAMrelated genes in MTB samples with diverse drug resistance profiles. The novel gene expression pattern in this work is valuable knowledge that can be applied for TB monitoring and treatment in the future.

Background and objectives: The pandemic of COVID-19 is a global concern requiring urgent and effective action. However, the data on prevention practices and the impact of COVID-19 among the Thai population have not been clearly described. This study aimed to examine the knowledge, attitudes, perception, practices, and factors predicting practices in the prevention of COVID-19 and to study the impact of COVID-19 on people’s livelihoods. Materials and Methods: A cross-sectional study was performed between April and November 2020. A questionnaire eliciting demographic data and information on knowledge, attitudes, perception, prevention practices, and impact of COVID-19 was given to 500 people who lived in Chiang Mai, and 480 usable questionnaires were returned, for a response rate of 96.0%. Data were analyzed using descriptive statistics and multivariate linear regression. Results: Less than half of the participants had a high level of knowledge (45.4%) about COVID-19. Most of them had a high level of attitudes (95.6%), perception (72.1%), and prevention practices (90.4%). Female (β = 0.11, p = 0.006), patient status (β = 0.17, p < 0.001), knowledge (β = −0.10, p = 0.020), attitudes (β = 0.37, p < 0.001), and perception (β = 0.21, p < 0.001) about COVID-19 prevention were the predicting factors for overall prevention practices (R2 = 0.288). Most participants perceived the overall impact of COVID-19 at moderate and high levels (47.1 and 37.8%, respectively). The highest impact was an economic burden, followed by psychological, social, and physical impacts. Conclusions: Policymakers should enhance attitudes and perception about COVID-19 prevention to improve the COVID-19 prevention practices. This may help to reduce the new cases of COVID-19 and may result in reducing the impact of COVID-19 on people’s livelihoods.

Tuberculosis is a highly contagious disease caused by the Mycobacterium tuberculosis complex (MTBC). Although TB is treatable, multidrug-resistant, extensively drug-resistant, and totally drug-resistant forms of M. tuberculosis have become a new life-threatening concern. New anti-TB drugs that are capable of curing these drug-resistant strains are urgently needed. The purpose of this study is to determine the antimycobacterial activity of D-enantiomer human lactoferricin 1-11 (D-hLF 1-11) against mycobacteria in vitro using a 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide colorimetric assay, resazurin microplate assay, and microscopic observation drug susceptibility assay. Three previously described antimicrobial peptides, protegrin-1, AK 15-6, and melittin, with potent anti-TB activity, were included in this study. The findings suggest that D-hLF 1-11 can inhibit the growth of M. tuberculosis with a minimum inhibitory concentration of 100–200 µg/mL in susceptible, isoniazid (INH)-monoresistant, rifampicin (RF)-monoresistant, and MDR strains. The peptide can also inhibit some nontuberculous mycobacteria and other MTBC in similar concentrations. The antibiofilm activity of D-hLF 1-11 against the biofilm-forming M. abscessus was determined by crystal violet staining, and no significant difference is observed between the treated and untreated biofilm control. The checkerboard assay was subsequently carried out with M. tuberculosis H37Rv and the results indicate that D-hLF 1-11 displays an additive effect when combined with INH and a synergistic effect when combined with RF, with fractional inhibitory concentration indices of 0.730 and 0.312, respectively. The red blood cell hemolytic assay was initially applied for the toxicity determination of D-hLF 1-11, and negligible hemolysis (<1%) was observed, despite a concentration of up to 4 mg/mL being evaluated. Overall, D-hLF 1-11 has potential as a novel antimycobacterial agent for the future treatment of drug-sensitive and drug-resistant M. tuberculosis infections.

Isoniazid (INH) is an antibiotic that is widely used to treat tuberculosis (TB). Adaptation to environmental stress is a survival strategy for Mycobacterium tuberculosis and is associated with antibiotic resistance development. Here, mycobacterial adaptation following INH treatment was studied using a multi-stress system (MS), which mimics host-derived stress. Mtb H37Rv (drug-susceptible), mono-isoniazid resistant (INH-R), mono-rifampicin resistant (RIF-R), and multidrug-resistant (MDR) strains were cultivated in the MS with or without INH. The expression of stress-response genes (hspX, tgs1, icl1, and sigE) and lipoarabinomannan (LAM)-related genes (pimB, mptA, mptC, dprE1, dprE2, and embC), which play important roles in the host–pathogen interaction, were measured using real-time PCR. The different adaptations of the drug-resistant (DR) and drug-susceptible (DS) strains were presented in this work. icl1 and dprE1 were up-regulated in the DR strains in the MS, implying their roles as markers of virulence and potential drug targets. In the presence of INH, hspX, tgs1, and sigE were up-regulated in the INH-R and RIF-R strains, while icl1 and LAM-related genes were up-regulated in the H37Rv strain. This study demonstrates the complexity of mycobacterial adaptation through stress response regulation and LAM expression in response to INH under the MS, which could potentially be applied for TB treatment and monitoring in the future.

Tuberculosis (TB) therapy requires long-course multidrug regimens leading to the emergence of drug-resistant TB and increased public health burden worldwide. As the treatment strategy is more challenging, seeking a potent non-antibiotic agent has been raised. Propolis serve as a natural source of bioactive molecules. It has been evidenced to eliminate various microbial pathogens including Mycobacterium tuberculosis (Mtb). In this study, we fabricated the niosome-based drug delivery platform for ethanolic extract of propolis (EEP) using thin film hydration method with Ag85A aptamer surface modification (Apt-PEGNio/EEP) to target Mtb. Physicochemical characterization of PEGNio/EEP indicated approximately −20 mV of zeta potential, 180 nm of spherical nanoparticles, 80% of entrapment efficiency, and the sustained release profile. The Apt-PEGNio/EEP and PEGNio/EEP showed no difference in these characteristics. The chemical composition in the nanostructure was confirmed by Fourier transform infrared spectrometry. Apt-PEGNio/EEP showed specific binding to Mycobacterium expressing Ag85 membrane-bound protein by confocal laser scanning microscope. It strongly inhibited Mtb in vitro and exhibited non-toxicity on alveolar macrophages. These findings indicate that the Apt-PEGNio/EEP acts as an antimycobacterial nanoparticle and might be a promising innovative targeted treatment. Further application of this smart nano-delivery system will lead to effective TB management.