Human tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent. In this study, the effects of TQ on intracellular mycobacterial replication are examined in macrophages. In addition, its effect on mycobacteria-induced NO production and pro-inflammatory responses were investigated in Mycobacterium tuberculosis (MTB)-infected Type II human alveolar and human myeloid cell lines. TQ at concentrations ranging from 12.5 to 25 μg/mL and 6.25 to 12.5 μg/mL reduced intracellular M. tuberculosis H37Rv and extensively drug-resistant tuberculosis (XDR-TB) 72 h post-infection in RAW 264.7 cells. TQ treatment also produced a concentration-dependent reduction in nitric oxide production in both H37Rv and XDR-TB infected RAW 264.7 cells. Furthermore, TQ reduced the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory molecules such as tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6) in H37Rv-infected cells and eventually reduced pathogen-derived stress in host cells. TQ inhibits intracellular H37Rv and XDR-TB replication and MTB-induced production of NO and pro-inflammatory molecules. Therefore, along with its anti-inflammatory effects, TQ represents a prospective treatment option to combat Mycobacterium tuberculosis infection.

The checkerboard assay is a well-established tool used to determine the antimicrobial effects of two compounds in combination. Usually, data collected from the checkerboard assay use visible turbidity and optical density as a readout. While helpful in traditional checkerboard assays, these measurements become less useful in a polymicrobial context as they do not enable assessment of the drug effects on the individual members of the community. The methodology described herein allows for the determination of cell viability through selective and differential plating of each individual species in a community while retaining much of the high-throughput nature of a turbidity-based analysis and requiring no specialized equipment. This methodology further improves turbidity-based measurements by providing a distinction between bacteriostatic versus bactericidal concentrations of antibiotics. Herein, we use this method to demonstrate that the clinically used antibiotic combination of ceftazidime and gentamicin works synergistically against Pseudomonas aeruginosa in monoculture but antagonistically in a polymicrobial culture also containing Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecalis, highlighting the fundamental importance of this methodology in improving clinical practices. We propose that this method could be implemented in clinical microbiology laboratories with minimal impact on the overall time for diagnosis.

Zika virus (ZIKV) is an aedes mosquito borne pathogen belonging to the member of flaviviridae subgroup is the causative agent of an emerging disease called Zika fever, known as a benign infection usually presenting as influenza like illness with cutaneous rash. Due to recent epidemic outbreaks it is realized as a major health risk which need enhanced surveillance, but no attempt has been made to design an epitope based peptide vaccine against Zika virus. Viral envelope proteins are derived from host cell membrane proteins with some viral glycoproteins and are used to cover their protective protein capsid, help the viruses to enter host cells and help them to avoid the host immune response. In this study, amino acid sequence of ZIKV envelope glycoprotein was obtained from a protein database and examined with in silico approaches to determine the most immunogenic epitopes for B cell and T cell which could induce humoral as well as cell mediated immune response. Both the linear and conformational epitopes for B cell were predicted by immunoinformatics tools housed in IEDB resources. The peptide sequence DAHAKRQTVVVLGSQEGAV from position 121 and peptide sequence from 117-137 amino acids were predicted as most potential B cell linear and conformational epitopes respectively. Epitopes for CD4+ and CD8+ T cell were also predicted by using tools within IEDB resource and peptide sequence MMLELDPPF from position 250-258 amino acids was predicted as most immunogenic CD8+ T cell epitope with immune response evoking ability prediction score (I pMHC) of 0.09139 and conservancy of 52.17%. The innate immune response for ZIKV envelope glycoprotein was determined by interferon (IFN)-gamma effectuation and mimicking capacity by immunoinformatics and molecular docking study respectively. However, this is an introductory approach to design an epitope based peptide vaccine against Zika virus; we hope this model will be very much helpful in designing and predicting novel vaccine candidate.

The swift rise of antibiotic resistance, coupled with limited new antibiotic discovery, presents a significant hurdle to global public health, demanding innovative therapeutic solutions. Recently, collateral sensitivity (CS), the phenomenon in which resistance to one antibiotic increases vulnerability to another, has come to light as a potential path forward in this attempt. Targeting either unidirectional or reciprocal CS holds promise for constraining the emergence of drug resistance and notably enhancing treatment outcomes. Typically, the alteration of bacterial physiology, such as bacterial membrane potential, expression of efflux pumps, cell wall structures, and endogenous enzymatic actions, are involved in evolved collateral sensitivity. In this review, we present a thorough overview of CS in antibiotic therapy, including its definition, importance, and underlying mechanisms. We describe how CS can be exploited to prevent the emergence of resistance and enhance the results of treatment, but we also discuss the challenges and restrictions that come with implementing this practice. Our review underscores the importance of continued exploration of CS mechanisms in the broad spectrum and clinical validation of therapeutic approaches, offering insights into its role as a valuable tool in combating antibiotic resistance.

The human microbiota is an array of microorganisms known to interact with the host and other microbes. These interactions can be competitive, as microbes must adapt to host- and microorganism-related stressors, thus producing toxic molecules, or cooperative, whereby microbes survive by maintaining homeostasis with the host and host-associated microbial communities. As a result, these microbial interactions shape host health and can potentially result in disease. In this review, we discuss these varying interactions across microbial species, their positive and negative effects, the therapeutic potential of these interactions, and their implications on our knowledge of human well-being.