Plant salinity stress, sensing, and its mitigation through WRKY.

Salinity or salt stress has deleterious effects on plant growth and development. It imposes osmotic, ionic, and secondary stresses, including oxidative stress on the plants and is responsible for the reduction of overall crop productivity and therefore challenges global food security. Plants respond to salinity, by triggering homoeostatic mechanisms that counter salt-triggered disturbances in the physiology and biochemistry of plants. This involves the activation of many signaling components such as SOS pathway, ABA pathway, and ROS and osmotic stress signaling. These biochemical responses are accompanied by transcriptional modulation of stress-responsive genes, which is mostly mediated by salt-induced transcription factor (TF) activity. Among the TFs, the multifaceted significance of WRKY proteins has been realized in many diverse avenues of plants' life including regulation of plant stress response. Therefore, in this review, we aimed to highlight the significance of salinity in a global perspective, the mechanism of salt sensing in plants, and the contribution of WRKYs in the modulation of plants' response to salinity stress. This review will be a substantial tool to investigate this problem in different perspectives, targeting WRKY and offering directions to better manage salinity stress in the field to ensure food security.

Transcriptional Regulation of Small Heat Shock Protein 17 (sHSP-17) by Triticum aestivum HSFA2h Transcription Factor Confers Tolerance in Arabidopsis under Heat Stress.

Heat shock transcription factors (HSFs) contribute significantly to thermotolerance acclimation. Here, we identified and cloned a putative HSF gene (HSFA2h) of 1218 nucleotide (acc. no. KP257297.1) from wheat cv. HD2985 using a de novo transcriptomic approach and predicted sHSP as its potential target. The expression of HSFA2h and its target gene (HSP17) was observed at the maximum level in leaf tissue under heat stress (HS), as compared to the control. The HSFA2h-pRI101 binary construct was mobilized in Arabidopsis, and further screening of T3 transgenic lines showed improved tolerance at an HS of 38 °C compared with wild type (WT). The expression of HSFA2h was observed to be 2.9- to 3.7-fold higher in different Arabidopsis transgenic lines under HS. HSFA2h and its target gene transcripts (HSP18.2 in the case of Arabidopsis) were observed to be abundant in transgenic Arabidopsis plants under HS. We observed a positive correlation between the expression of HSFA2h and HSP18.2 under HS. Evaluation of transgenic lines using different physio-biochemical traits linked with thermotolerance showed better performance of HS-treated transgenic Arabidopsis plants compared with WT. There is a need to further characterize the gene regulatory network (GRN) of HSFA2h and sHSP in order to modulate the HS tolerance of wheat and other agriculturally important crops.

Uric acid and diabetes mellitus: an update.

The relationship between diabetes mellitus (DM) and high serum uric acid is complex and controversial. Many epidemiological studies have reported a positive association, whereas others have reported an inverse association or none. In the pathogenesis of DM it is the intracellular urate that is more important than the extracellular and dissociation between the two is possible. Evidence suggests that high serum uric acid induces insulin resistance and beta cell failure in animal models. Reduction of intracellular uric acid can be achieved by dietary measures such as reducing fructose and salt intake, and uric acid-lowering drugs. We suggest that in the Western diet, these elements play a crucial role in pathogenesis of DM. To determine the precise and exact interrelationship between intracellular and extracellular uric acid, well-designed studies are required. Besides this, clinical trials are needed to determine whether intracellular and extracellular urate reduction will provide benefit in prevention and treatment of DM and complications associated with it.

Effect of mineral elements on the formation of gallbladder stones using spectroscopic techniques.

Long-standing gallbladder stones have been recognized as one of the highest risk factors for gallbladder cancer. However, the growth and progression of gallbladder stones are still not well-known, and their uncovering requires accurate information on the formation/nucleation and complex compositional information of gallstones. Multiple and single gallstones are analyzed using laser-induced breakdown spectroscopy (LIBS), photoacoustic spectroscopy (PAS), and Fourier transform infrared spectroscopy (FTIR). Spectral signatures as well as spatial variation in the spectral intensities of different elements are observed in the LIBS spectra of the gallstones. In the multiple-type gallstones, the concentration of inorganic content increases from core to periphery, whereas a single gallstone shows the opposite trend from the point of nucleation/core. It is suggested that the concentration of inorganic elements (Mg, Ca, K, and Na) plays an important role in the nucleation and growth of gallstones; thus, accordingly, multiple- and single-type gallstones are found in the gallbladder. The presence of different electronic bands of molecules, such as CH, C2, CN, and NH, is confirmed by LIBS and FTIR. PAS has identified molecules, such as cholesterol, calcium carbonate, and calcium phosphate, in different gallstone samples. These results show that PAS combined with LIBS is a promising candidate for the compositional analysis of gallstones. Furthermore, principal component analysis (PCA) is used to discriminate different layers present in the gallstones.

Quantitative analysis of human hairs and nails.

Hair and nails are human biomarkers capable of providing a continuous assessment of the concentrations of elements inside the human body to indicate the nutritional status, metabolic changes, and the pathogenesis of various human diseases. Laser-induced breakdown spectroscopy (LIBS) and X-ray fluorescence (XRF) spectrometry are robust and multi-element analytical techniques able to analyze biological samples of various kinds for disease diagnosis. The primary objective of this review article is to focus on the major developments and advances in LIBS and XRF for the elemental analysis of hair and nails over the last 10-year period. The developments in the qualitative and quantitative analyses of human hair and nail samples are discussed in detail, with special emphasis on the key aspects of elemental imaging and distribution of essential and non-essential elements within the hair and nail tissue samples. Microchemical imaging applications by LIBS and XRF (including micro-XRF and scanning electron microscopy, SEM) are also presented for healthy as well as diseased tissue hair and nail samples in the context of disease diagnosis. In addition, main challenges, prospects, and complementarities of LIBS and XRF toward analyzing human hair and nails for disease diagnosis are also thoroughly discussed here.

Discrimination of gallbladder stone employing Laser-Induced Breakdown Spectroscopy (LIBS) and Photoacoustic Spectroscopy (PAS).

Compositional analysis of gallstone samples has been carried out, using Laser-Induced Breakdown Spectroscopy (LIBS) and Photoacoustic Spectroscopy (PAS). Classification of gallstone has been made on the basis of intensities of the inorganic and organic constituents present in the LIBS spectra. A regression plot is drawn between LIBS spectral intensities of organic & inorganic elements and the stoichiometric ratio of Cholesterol, Bilirubin and Calcium Carbonate. Atomic lines of various elements, as well as molecular signatures of CaO Orange band, CN Violet band, and C2 Swan band, are observed in LIBS spectra. The relative hardness of gallstones is estimated from the intensity ratio of ionic to neutral atomic lines of the species observed in LIBS spectra. PAS is used for detecting molecular constituents in the gallstones. Principal Component Analysis (PCA) is performed for the discrimination of gallstones. It is found that PAS data, in combination with LIBS provide a suitable method for the compositional analysis of gallstones.

Insights into decontamination of soils by phytoremediation: A detailed account on heavy metal toxicity and mitigation strategies.

In the current era of rapid industrialization, the foremost challenge is the management of industrial wastes. Activities such as mining and industrialization spill over a large quantity of toxic waste that pollutes soil, water, and air. This poses a major environmental and health challenge. The toxic heavy metals present in the soil and water are entering the food chain, which in turn causes severe health hazards. Environmental clean-up and reclamation of heavy metal contaminated soil and water are very important, and it necessitates efforts of environmentalists, industrialists, scientists, and policymakers. Phytoremediation is a plant-based approach to remediate heavy metal/organic pollutant contaminated soil and water in an eco-friendly, cost-effective, and permanent way. This review covers the effect of heavy metal toxicity on plant growth and physiological process, the concept of heavy metal accumulation, detoxification, and the mechanisms of tolerance in plants. Based on plants' ability to uptake heavy metals and metabolize them within tissues, phytoremediation techniques have been classified into six types: phytoextraction, phytoimmobilization, phytovolatilization, phytodegradation, rhizofiltration, and rhizodegradation. The development of research in this area led to the identification of metal hyper-accumulators, which could be utilized for reclamation of contaminated soil through phytomining. Concurrently, breeding and biotechnological approaches can enhance the remediation efficiency. Phytoremediation technology, combined with other reclamation technologies/practices, can provide clean soil and water to the ecosystem.

Analysis of stones formed in the human gall bladder and kidney using advanced spectroscopic techniques.

Stone diseases (gallstones and kidney stones) are extremely painful and often cause death. The prime aim of biomedical research in this area has been determination of factors resulting in stone formation inside the gallbladder and urinary tract. Many theories have been put forward to explain the mechanism of stone formation and their growth; however, their complete cycle of pathogenesis is still under debate. Several factors are responsible for stone formation; however, much emphasis is placed on the determination of elemental and molecular composition of the stones. In the present review article, we describe different kinds of spectroscopic techniques such as Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence (XRF) spectroscopy, time-of-flight secondary ion mass spectrometry (TOF-SIMS), and laser-induced breakdown spectroscopy (LIBS) and highlight their use in the analysis of stone diseases. We have summarized work done on gallstones and kidney stones using these advanced techniques particularly over the last 10 years. We have also briefly elaborated the basics of stone formations inside the human body and their complications for a better understanding of the subject.

Mercury-Induced Inhibition of Tyrosine Phosphorylation of Sperm Proteins and Altered Functional Dynamics of Buck Spermatozoa: an In Vitro Study.

Present study was undertaken on buck spermatozoa to investigate the effect of mercuric chloride on functional dynamics of buck spermatozoa. Four different concentrations (0.031, 0.125, 0.25 and 1.25 µg/mL) of mercuric chloride, which were 1/40th, 1/10th, 1/5th and equivalent to the LC50 value of HgCl2, were selected for studying their effect following in vitro exposure for 15 min and 3 h. Exposure of spermatozoa to 0.031 µg/mL mercuric chloride for 3 h resulted in significant (p < 0.05) decrease in sperm motility, sperm having intact membrane, intact acrosome and high mitochondrial trans-membrane potential. However, following exposure to higher concentrations (0.25, 1.25 µg/mL), similar results were observed even after 15 min of exposure. HgCl2 significantly (p < 0.05) increased the levels of malondialdehyde and reactive oxygen species and significantly (p < 0.05) decreased total antioxidant capacity and superoxide dismutase activity in spermatozoa within 15 min of exposure. Mercuric chloride-treated spermatozoa did not show capacitation, rather exhibited spontaneous acrosome reaction along with significant increase in intracellular Ca2+ and cAMP levels. Immuno-blotting of semen samples of control and 0.031 µg/mL mercury-treated groups showed low intensity bands of p55, p70, p80, p105 and p190 kDa tyrosine phosphorylation proteins while higher concentration-treated groups showed no such bands. Our findings evidently suggest that mercuric chloride even at 0.031 µg/mL adversely affected sperm functions, inhibited tyrosine phosphorylation proteins and capacitation due to oxidative stress. Spontaneous acrosome reaction (AR) in mercury-treated spermatozoa may possibly be due to increase in intracellular Ca2+ and cAMP levels, and capacitation failure may be due to inhibition of tyrosine phosphorylation of proteins.

Poly-ß-Hydroxybutyrate Production by the Cyanobacterium Scytonema geitleri Bharadwaja under Varying Environmental Conditions.

The production of poly-ß-hydroxybutyrate (PHB) under varying environmental conditions (pH, temperature and carbon sources) was examined in the cyanobacterium Scytonema geitleri Bharadwaja isolated from the roof-top of a building. The S. geitleri produced PHB and the production of PHB was linear with the growth of cyanobacterium. The maximum PHB production (7.12% of dry cell weight) was recorded when the cells of S. geitleri were at their stationary growth phase. The production of PHB was optimum at pH 8.5 and 30 °C, and acetate (30 mM) was the preferred carbon source.

A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis.

BACKGROUND: The clinical trials conducted at Chingleput India suggest that BCG fails to protect against tuberculosis (TB) in TB-endemic population. Recent studies advocate that non-tuberculous mycobacteria and latent Mycobacterium tuberculosis (Mtb) infection interferes in the antigen processing and presentation of BCG in inducing protective immunity against Mtb. Thereby, indicating that any vaccine that require extensive antigen processing may not be efficacious in TB-endemic zones. Recently, we have demonstrated that the vaccine candidate L91, which is composed of lipidated promiscuous MHC-II binder epitope, derived from latency associated Acr1 antigen of Mtb is immunogenic in the murine and Guinea pig models of TB and conferred better protection than BCG against Mtb. METHODS: In this study, we have used a multi-stage based bi-epitope vaccine, namely L4.8, comprising of MHC-I and MHC-II binding peptides of active (TB10.4) and latent (Acr1) stages of Mtb antigens, respectively. These peptides were conjugated to the TLR-2 agonist Pam2Cys. RESULTS: L4.8 significantly elicited both CD8 T cells and CD4 T cells immunity, as evidenced by increase in the enduring polyfunctional CD8 T cells and CD4 T cells. L4.8 efficiently declined Mtb-burden and protected animals better than BCG and L91, even at the late stage of Mtb infection. CONCLUSIONS: The BCG-L4.8 prime boost strategy imparts a better protection against TB than the BCG alone. This study emphatically denotes that L4.8 can be a promising future vaccine candidate for controlling active and latent TB.

A lipidated peptide of Mycobacterium tuberculosis resuscitates the protective efficacy of BCG vaccine by evoking memory T cell immunity.

BACKGROUND: The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. METHODS: In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice. Female BALB/c mice were immunized with BCG. Later, they were boosted twice with L91 or an antigenically irrelevant lipidated influenza virus hemagglutinin peptide (LH). Further, PBMCs obtained from BCG vaccinated healthy subjects were cultured in vitro with L91. T cell responses were determined by surface markers and intracellular cytokine staining. Secretion of cytokines was estimated in the culture supernatants (SNs) by ELISA. RESULTS: Compared to the BCG-vaccinated controls, L91 booster significantly enhanced the percentage of memory Th1 cells and Th17 cells and reduced the mycobacterial burden in BCG primed and L91-boosted (BCG-L91) group, even after 229 days of BCG vaccination. Further, substantial augmentation in the central (CD44hiCD62LhiCD127hi) and effector memory (CD44hiCD62LloCD127lo) CD4 T cells was detected. Furthermore, greater frequency of polyfunctional Th1 cells (IFN-γ+TNF-α+) and Th17 cells (IFN-γ+IL-17A+) was observed. Importantly, BCG-L91 successfully prevented CD4 T cells from exhaustion by decreasing the expression of PD-1 and Tim-3. Additionally, augmentation in the frequency of Th1 cells, Th17 cells and memory CD4 T cells was observed in the PBMCs of the BCG-vaccinated healthy individuals following in vitro stimulation with L91. CONCLUSIONS: Our study demonstrated that L91 robustly reinvigorate BCG potency to invoke enduring protection against Mtb. This novel vaccination stratagem involving BCG-priming followed by L91-boosting can be a future prophylactic measure to control TB.

A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host.

Regardless of the fact that potent drug-regimen is currently available, tuberculosis continues to kill 1.5 million people annually. Tuberculosis patients are not only inflicted by the trauma of disease but they also suffer from the harmful side-effects, immune suppression and drug resistance instigated by prolonged therapy. It is an exigency to introduce radical changes in the existing drug-regime and discover safer and better therapeutic measures. Hence, we designed a novel therapeutic strategy by reinforcing the efficacy of drugs to kill Mtb by concurrently boosting host immunity by L91. L91 is chimera of promiscuous epitope of Acr1 antigen of Mtb and TLR-2 agonist Pam2Cys. The adjunct therapy using drugs and L91 (D-L91) significantly declined the bacterial load in Mtb infected animals. The mechanism involved was through enhancement of IFN-γ(+)TNF-α(+) polyfunctional Th1 cells and IL-17A(+)IFN-γ(+) Th17 cells, enduring memory CD4 T cells and downregulation of PD-1. The down-regulation of PD-1 prevents CD4 T cells from undergoing exhaustion and improves their function against Mtb. Importantly, the immune response observed in animals could be replicated using T cells of tuberculosis patients on drug therapy. In future, D-L91 therapy can invigorate drugs potency to treat tuberculosis patients and reduce the dose and duration of drug-regime.

Analysis of heterogeneous gallstones using laser-induced breakdown spectroscopy (LIBS) and wavelength dispersive X-ray fluorescence (WD-XRF).

Laser-induced breakdown spectroscopy (LIBS) is an emerging analytical technique with numerous advantages such as rapidity, multi-elemental analysis, no specific sample preparation requirements, non-destructiveness, and versatility. It has been proven to be a robust elemental analysis tool attracting interest because of being applied to a wide range of materials including biomaterials. In this paper, we have performed spectroscopic studies on gallstones which are heterogeneous in nature using LIBS and wavelength dispersive X-ray fluorescence (WD-XRF) techniques. It has been observed that the presence and relative concentrations of trace elements in different kind of gallstones (cholesterol and pigment gallstones) can easily be determined using LIBS technique. From the experiments carried out on gallstones for trace elemental mapping and detection, it was found that LIBS is a robust tool for such biomedical applications. The stone samples studied in the present paper were classified using the Fourier transform infrared (FTIR) spectroscopy. WD-XRF spectroscopy has been applied for the qualitative and quantitative analysis of major and trace elements present in the gallstone which was compared with the LIBS data. The results obtained in the present paper show interesting prospects for LIBS and WD-XRF to study cholelithiasis better.

Challenges and solutions for a rational vaccine design for TB-endemic regions.

Vaccines have been successful for global eradication or control of dreaded diseases such as smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles. Unfortunately, this success has not been achieved for controlling tuberculosis (TB) worldwide. Bacillus Calmette Guérin (BCG) is the only available vaccine against TB. Paradoxically, BCG has deciphered success in the Western world but has failed in TB-endemic areas. In this article, we highlight and discuss the aspects of immunity responsible for controlling Mycobacterium tuberculosis infection and factors responsible for the failure of BCG in TB-endemic countries. In addition, we also suggest strategies that contribute toward the development of successful vaccine in protecting populations where BCG has failed.

Triggering through Toll-like receptor 2 limits chronically stimulated T-helper type 1 cells from undergoing exhaustion.

Chronic infections result in T-cell exhaustion, a state of functional unresponsiveness. To control the infection, it is important to salvage the exhausted T cells. In this study, we delivered signals through Toll-like receptor 2 (TLR-2) to reinvigorate functionality in chronically activated T-helper type 1 (Th1) cells. This process significantly augmented the expression of T-bet, interferon γ, interleukin 2, and the antiapoptotic molecule Bcl-2, whereas it dampened the display of the exhaustion markers programmed death receptor 1 (PD-1) and lymphocyte activation gene 3 (Lag-3). Additionally, TLR-2 signaling bolstered the ability of chronically stimulated Th1 cells to activate B cells. Finally, the results were substantiated by observing reduced lung pathology upon administration of TLR-2 agonist in the chronic infection model of tuberculosis. These data demonstrated the importance of TLR-2 in rescuing chronically activated Th1 cells from undergoing exhaustion. This study will pave a way for targeting TLR-2 in developing therapeutic strategies to treat chronic diseases involving loss of Th1 cell function.

Decision-making critical amino acids: role in designing peptide vaccines for eliciting Th1 and Th2 immune response.

CD4 T cells play a cardinal role in orchestrating immune system. Differentiation of CD4 T cells to Th1 and Th2 effector subsets depends on multiple factors such as relative intensity of interactions between T cell receptor with peptide-major histocompatibility complex, cytokine milieu, antigen dose, and costimulatory molecules. Literature supports the critical role of peptide's binding affinity to Human Leukocyte Antigens (HLAs) and in the differentiation of naïve CD4 T cells to Th1 and Th2 subsets. However, there exists no definite report addressing very precisely the correlation between physicochemical properties (hydrophobicity, hydrophilicity), pattern, position of amino acids in peptide and their role in skewing immune response towards Th1 and Th2 cells. This may play a significant role in designing peptide vaccines. Hence in the present study, we have evaluated the relationship between amino acid pattern and their influence in differentiation of Th1 and Th2 cells. We have used a data set of 320 peptides, whose role has been already established experimentally in the generation of either Th1 or Th2 immune response. Further, characterization was done based on binding affinity, promiscuity, amino acid pattern and binding conformation of peptides. We have observed that distinct amino acids in peptides elicit either Th1 or Th2 immunity. Consequently, this study signifies that alteration in the sequence and type of selected amino acids in the HLA class II binding peptides can modulate the differentiation of Th1 and Th2 cells. Therefore, this study may have an important implication in providing a platform for designing peptide-based vaccine candidates that can trigger desired Th1 or Th2 response.

Kidney stone analysis techniques and the role of major and trace elements on their pathogenesis: a review.

Kidney stone disease is a polygenic and multifactorial disorder with a worldwide distribution, and its incidence and prevalence are increasing. Although significant progress has been made in recent years towards identifying the specific factors that contribute to the formation of kidney stone, many questions on the pathogenesis of kidney stones remain partially or completely unanswered. However, none of the proposed mechanisms specifically consider the role(s) of the trace elements and, consequently, the contribution of trace constituents to the pathogenesis of kidney stones remains unclear and under debate. The findings of some studies seem to support a role for some major and trace elements in the initiation of stone crystallization, including as a nucleus or nidus for the formation of the stone or simply as a contaminant of the stone structure. Thus, the analysis of kidney stones is an important component of investigations on nephrolithiasis in order to understand the role of trace constituents in the formation of kidney stones and to formulate future strategies for the treatment and prevention of stone formation and its recurrence. The aim of this review is to compare and evaluate the methods/procedures commonly used in the analysis of urinary calculi. We also highlight the role of major and trace elements in the pathogenesis of kidney stones.

Lipidated promiscuous peptide augments the expression of MHC-II molecules on dendritic cells and activates T cells.

BACKGROUND & OBJECTIVES: In spite of the fact that BCG is the most widely used vaccine, tuberculosis (TB) continues to be a major killer disease in TB-endemic regions. Recently, many emerging evidences from the published literature indicate the role of environmental mycobacteria in blocking the processing and presentation of BCG antigens and thereby impairing with suboptimal generation of protective T cells. To surmount this problem associated with BCG, we constructed a novel lipopeptide (L91) by conjugating a promiscuous peptide consisting of CD4 + T-helper epitope of sequence of 91-110 of 16 kDa antigen of Mycobacterium tuberculosis to Pam2Cys, an agonist of Toll-like receptor-2. METHODS: Mice were immunized subcutaneously with 20 nmol of L91, followed by a booster with 10 nmol, after an interval of 21 days of primary immunization. Animals were sacrificed after seven days of post-booster immunization. L91 induced immune response was characterized by the expression of MHC-II and CD74 on the surface of dendritic cells (DCs) by flowcytometry. Cytokines (IL-4, IL-10, IFN-γ) secretion and anti-peptide antibodies were measured by ELISA. RESULTS: Self-adjuvanting lipopeptide vaccine (L91) was directly bound to MHC-II molecules and without requiring extensive processing for its presentation to T cells. It stimulated and activated dendritic cells and augmented the expression of MHC-II molecules. Further, it activated effector CD4 T cells to mainly secrete interferon (IFN)-γ but not interleukin (IL)-4 and IL-10. L91 did not elicit anti-peptide antibodies. INTERPRETATION & CONCLUSIONS: The findings suggest that L91 evokes maturation and upregulation of MHC class II molecules and promotes better antigen presentation and, therefore, optimum activation of T cells. L91 mainly induces effector Th1 cells, as evidenced by predominant release of IFN-γ, consequently can mount favourable immune response against M. tuberculosis . As L91 does not provoke the generation of anti-peptide antibodies, there is no fear of the efficacy of the vaccine being neutralized by pre-existing anti-mycobacterial antibodies in TB-endemic population. In conclusion, L91 may be considered as a future potential candidate vaccine against TB.

Lipidated promiscuous peptides vaccine for tuberculosis-endemic regions.

Despite nine decades of Bacillus Calmette--Guérin (BCG) vaccination, tuberculosis continues to be a major global health challenge. Clinical trials worldwide have proved the inadequacy of the BCG vaccine in preventing the manifestation of pulmonary tuberculosis in adults. Ironically, the efficacy of BCG is poorest in tuberculosis endemic areas. Factors such as nontuberculous or environmental mycobacteria and helminth infestation have been suggested to limit the efficacy of BCG. Hence, in high TB-burden countries, radically novel strategies of vaccination are urgently required. Here we showcase the properties of lipidated promiscuous peptide vaccines that target and activate cells of the innate and adaptive immune systems by employing a Toll-like receptor-2 agonist, S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam2Cys). Such a strategy elicits robust protection and enduring memory responses by type 1 T helper cells (Th1). Consequently, lipidated peptides may yield a better vaccine than BCG.